# RQM+ > Evolving MedTech ### Posts #### “Toto…We're Not in Brussels Anymore”. Accounting for National Legislation on the Yellow Brick Road to CE marking By Ed Ball - Manager, Intelligence In our recent series of blogs on CE marking and medical devices in the EU, we have considered EU legislation beyond the EU MDR and IVDR 1, 2, we have explored Europe and the EU 3, and we have highlighted the benefits of a CE mark outside of the EU 4. In this blog we will discuss one more aspect; one that is often overlooked…national legislation. Once upon a time, medical device regulatory affairs folks were very familiar with national legislation in Europe. The three medical device directives (AIMDD, MDD and IVDD) all required transposing into national legislation to actually become laws. With the switch to EU regulations and the publication of the EU MDR and IVDR, national legislation has often taken a back seat in the wider discussions about regulatory requirements for CE marking. But does it still have a place? Is it still important? This blog will highlight six areas where national legislation plays an important role in the implementation of the MDR and IVDR. Languages Now we all know the first official languages of the EU, don’t we? No prizes for guessing that it wasn’t English. Anyone that is responsible for labelling and instructions for use content, or translations will be able to tell you (hopefully) that there are 24 official languages in the EU (ranging from Bulgarian to Swedish) 5. Then there are those official languages of other countries for which the EU MDR and IVD apply, such as Icelandic, Norwegian, and Turkish. The MDR Article 10(11) and the IVDR Article 10(10) both require the information set out in Annex I (i.e. the GSPRs) to be available in “an official Union language as determined by the Member State”. The IVDR then has the same requirement for the information provided with IVDs for self-testing or near-patient testing, with the addition that the information must be “easily understandable”. This opens the door for the logical consideration that not all users are the same, and thus their language requirements may differ. The Member States are not obliged to legally specify the languages(s) to be used. Sensibly, to avoid any confusion in the implementation of this requirement, and then the assessment of conformity against this requirement, many Member States have published clear legislation or guidance on their official language(s) to be used as part of labelling and information for use. Some Member States have gone one step further and clarified that devices intended solely for use by healthcare professionals can be provided in one language (e.g. English) whilst devices intended for use by non-professionals must be provided in at least one of the native languages of that Member State. Keeping track of all that can be a challenge. Thankfully, the European Commission have published reference documents for the MDR and IVDR 6, detailing all of the national provisions where Member States have opted for legally defining the language requirements for medical device manufacturers. This covers not just the labelling, instructions for use and the implant card, but also the Declaration of Conformity, Technical Documentation and Field Safety Notices (See examples in Figure 1). Figure 1: Example of language requirements in some European Countries A word of warning though…the languages specified by the Member States are the bare minimum. Depending on your target markets and intended user groups and patient populations, there may be languages spoken by a small but not insignificant population. From a risk management and usability perspective, this should be considered in addition to the baseline regulatory requirement. Clinical Investigations & Performance Studies The requirements for clinical investigations and performance studies include authorisation by the Member State(s) in which the investigation/study will take place, and an ethical review in accordance with national law (MDR Art 62 and Annex XV; IVDR Art 58 and Annex XIV). Given the complexity of clinical investigation submissions, it makes sense for Member States to provide some structure here. Just like with the language requirements, many member states have laid down legislation prescribing the authorisation requirements for clinical investigations and performance studies 7-11. Other Member States prefer to keep this as guidance rather than legislation, which allows it to be more dynamic and updated more easily as and when necessary 12. Reprocessing of Single-Use Devices “Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.” MDR 2017/745 Article 17 (1) That’s nice and clear. The reprocessing of single-use devices needs to be permitted by national law in a specific Member State before any of the subsequent MDR requirements in Article 17 are considered. For those organisations involved with reprocessing single-use devices (and those manufacturers with single-use devices who know or suspect that their devices are being reprocessed), this could be a complicated situation to keep track of. It is, but the Commission do make it slightly easier by providing a whole section of their website devoted to reprocessing of single-use devices 13. Member States are obliged to inform the Commission of their national provisions on this subject, and the Commission then share that information. Thus, we know that the many Member States do not authorise reprocessing of single-use devices on their territory (See Figure 2). For those Member States that do authorise reprocessing of single-use devices, we are provided with a summary of which parts of Article 17 are permitted, not permitted and restricted; plus links to the national legislation also. Figure 2. Summary of which Member States authorise reprocessing of single-use devices Custom-Made Devices The EU MDR contains various requirements relating to custom made devices (e.g. Article 2 (3), Article 21, Article 52 (8), Annex XIII), as well as correcting my favourite typo from the MDD 93/42/EEC (Essential Requirement 13.3 g if you never spotted it). A key principle of a custom-made device is that it is made specifically in accordance with a written prescription to meet the needs of a specific patient 14. The person issuing the prescription must be authorised by national law on the basis of their professional qualifications etc. The prescribing individual does not necessarily have to be a healthcare professional 15 as long as they are authorised to prescribe by the applicable national legislation in each Member State. For manufacturers of custom-made devices operating across multiple Member States, it becomes critical to understand, in each Member State, who is authorised to prescribe, and equally what they are authorised to prescribe (e.g. it may not be appropriate for a dentist to prescribe an ankle-foot orthosis). The New Kid on the Block Regulation (EU) 2024/1860 introduced Article 10a to the EU MDR and IVDR regarding the notification of interruptions in the supply of medical devices and the discontinuation of medical devices. Whilst the text of Article 10a does not strictly rely upon national laws for implementation, it is similar to the vigilance system until such time that EUDAMED is operational. By that, it is meant that the legal requirement involves a notification to the competent authority of the Member State where the device manufacturer, or its authorised representative, is established. Each competent authority must then establish, and communicate, how they wish to receive these notifications. Some have established elements of this in national law 16, 17, whilst others have simply communicated this via their website 18-20. The publication of the notification template 21 provides a consistent format for the notifications, and many competent authorities have set-up specific email addresses to receive the notifications (See Figure 3). As well as communicating the notification to the other affected competent authorities (as per Article 10a (2)), it is assumed that each competent authority then has their own process for how to manage such a notification in their own territory depending on the structure of their healthcare system. Figure 3. Illustration of Article 10a notification sequence with examples of Competent Authority contact points And Last but Not Least If the above discussion of a select few requirements tied to national legislation is giving you a headache, or worse, then spare a thought for your friendly notified body reviewers. As part of the MDR and IVDR requirements for notified body competence (Annex VII), notified bodies must verify that their personnel are aware of “Union and national law in force on devices”. That should mean… for all Member States. Sounds delightful! Rest assured, they will probably be verifying the same aspect of competence thing during conformity assessments of device manufacturers. Summary The purpose of this blog was not to scare anyone, but to highlight the role that national legislation plays in the CE marking process with several examples provided. The EU MDR and IVDR are the main focus of course, but there are many horizontal EU regulations and more pieces of national legislation that we need to be mindful of when establishing our regulatory strategies, our design and development plans, our quality management system processes and our post-market surveillance processes 22. Related next steps If you’re having difficulty navigating the EU regulatory landscape and struggling to comply with horizontal EU regulations, our experts specialise in helping manufacturers develop comprehensive regulatory strategies designed to ensure that medical devices and IVDs comply with all applicable EU legislation. Contact us to discuss how we can support your efforts and stay tuned for more updates related to the European Medical Device landscape in our upcoming blog posts. Recent Developments in EU Horizontal Legislation Medical Devices, IVDs and Other EU Laws Europe, the EU, and the EU Single Market: geopolitical implications for MedTech Where can your CE mark take you next? Languages (European Union) Overview of language requirements for manufacturers of medical devices S.I. No. 261 of 2021 Medical Devices Regulations 2021 Ordonnance n° 2022-582 du 20 avril 2022 portant adaptation du droit français au règlement (UE) 2017/745 du Parlement européen et du Conseil du 5 avril 2017 relatif aux dispositifs médicaux Décret n° 2024-795 du 8 juillet 2024 relatif aux investigations cliniques et aux études des performances Act of 24 October 2019, containing rules on the safety and quality of medical devices (Medical Devices Act) Royal decree implementing the law of 22 December 2020 on medical devices Danish Medicines Agency - Clinical investigation of medical devices National rules on reprocessing of single-use devices Custom-made devices MDCG 2021-3 - Questions and Answers on Custom-made devices & considerations on adaptable medical devices and Patient-matched medical devices Law on the implementation of EU provisions concerning medical devices (Medical Devices Law Implementation Act - MPDG) Section 7a Procedure for the obligation to provide information pursuant to Article 10a of Regulation (EU) 2017/745 and Article 10a of Regulation (EU) 2017/746 BfArM - Notification of interruptions or discontinuations of the supply of a medical device ANSM - Report a discontinuation or discontinuation of a medical device or in vitro diagnostic medical device FAMHP - Obligation for manufacturers to notify interruptions or discontinuations in the supply of medical devices and in vitro diagnostic medical devices MHRA - Notification of interruption or discontinuation of the supply of a medical device for manufacturers based in Northern Ireland MDCG 2024 – 16 Manufacturer Information Form on Interruption or Discontinuation of Supply of certain medical devices and certain in vitro diagnostic medical devices (as per Article 10a of Regulation (EU) 2024/1860 amending Regulation (EU) 2017/745 and Regulation (EU) 2017/746) Enhancing Competitiveness in MedTech: Smart Strategies with Regulatory Intelligence #### 5 Key Elements of GMP in the Food Industry Good manufacturing practice (GMP) is a critical part of the quality assurance and control (QA/QC) pipeline for food contact materials, from primary packaging through to kitchenware. Although GMP principles were established by the US Food and Drug Administration (FDA), they were designed as a framework of accountability where the minimum benchmark of quality exceeds the compliance parameters for various market regulations; including those setup by the European Commission. GMP principles run the gamut in terms of addressable areas, but they are also deliberately flexible. As such, GMP in food industry checklists often range from as few as three key principles to more than ten. At RQM+ Lab Services, we believe there are five key elements of GMP in the food industry which you should be aware of. 1. Primary Materials GMP in the food industry is primarily concerned with food contact materials – sometimes abbreviated to FCM. It is necessary for FCMs and their constituents to be sufficiently inert so that they pose no risk to consumers and will not influence the quality of the product. Adhering to this from a current GMP (cGMP) perspective demands the stringent adoption of singular formulae without deviation throughout the manufacturing cycle. Essentially, manufacturers must verify the efficacy of candidate materials, and exclusively utilize the best primary materials for FCMs. 2. Facilities & Equipment The next thing to consider is the standard of your premises. Everything from the research and development (R&D) laboratory to the packaging line must be properly maintained to guarantee that all working conditions are fit for food production. Key GMP considerations here span from the most basic of cleaning standards through to critical equipment servicing, which mitigates the risk of contamination from the processing equipment or the facility itself. 3. Personnel Employee hygiene is another critical aspect of GMP in the food industry. Cleanliness is by-and-large second nature to most employees in food manufacturing and packaging facilities, but it is crucial to go beyond encouragement and to make cleanliness a documented habit. Food contamination from poor hygiene can lead to issues of non-compliance. Training personnel in the relevant hygiene regulations and providing the necessary equipment for avoiding human contact with products, is essential to building a skilled workforce which routinely operates within the GMP framework. 4. Procedures The FDA expects companies to use modern equipment for all procedures. As the remit of cGMP principles is extremely broad, it is impossible for the regulator to establish individual checklists of verified equipment for every procedure. Instead, companies should use equipment and procedures which are reasonably up-to-date, and should be able to validate the quality of those procedures if/when audited.   5. Documentation Though last on the list, the concept of documentation is not a final consideration in GMP food standards. It runs in tandem with all four elements on this GMP checklist. Manufacturers should look to build quality into every step of the manufacturing chain, and to do that, it is important to document every pertinent detail to ensure full accountability. Naturally, all documentation should be written in plain, professional language and should be easy to follow. Food Industry GMP with RQM+ Lab Services Most manufacturers, packagers, and processors of food goods adhere to strict internal standards which are sufficient for cGMP standards, but there is often an element of uncertainty. RQM+ Lab Services is a trusted partner with years of experience in lab analysis for a wide range of applications. If you would like to learn more about our GMP food contact material compliant services, why not contact a member of the team today? #### 5 Tips for IVDR Certification of Companion Diagnostics Introduction The pathway to IVDR certification for companion diagnostics (CDx) can be overwhelming due to the complexity of the certification process. Certification from a notified body was not previously required, as they were self-certified under IVDD. In addition, certification to IVDR requires an external consultation process (note that the information provided in this blog post is specific to consultation with the European Medicines Agency, EMA ). The 5 tips below will help you prepare for your notified body review and external consultation for your CDx. Also, if you would like to learn how RQM+ can support your specific IVD-related projects, please let us know. 1. Know the differences between companion diagnostics in the US versus EU Since companion diagnostics were previously self-certified under IVDD, the only experience with regulatory approval that many CDx manufacturers have is with FDA. When working towards IVDR certification, it is important to understand the differences between the definition of CDx between FDA and IVDR. In the EU under IVDR, CDx is defined as a device which is essential for the safe and effective use of a corresponding medicinal product to identify, before and/or during treatment: Patients who are most likely to benefit from the corresponding medicinal product Patients likely to be at increased risk of serious adverse reaction as a result of treatment with a corresponding medicinal product A similar definition exists for FDA; however, the FDA definition also includes devices used to monitor response to treatment with a particular therapeutic product, for the purpose of adjusting treatment to achieve improved safety or effectiveness. This last indication is not present in the EU definition, and devices used for monitoring a treatment response are not considered companion diagnostics. In addition, the FDA recognizes a related class of devices known as complementary diagnostics. These are defined as tests that identify a biomarker-defined subset of patients that responds well to a drug and aid risk/benefits assessments for individual patients, but that are not a prerequisite for receiving the drug. Complementary diagnostics are not defined in the IVDR and do not require any special considerations for CE marking. When preparing for the conformity assessment process for IVDR, be sure to consider the differences between the US and EU regulations and create your technical file accordingly. For devices that have already gone through FDA approvals, this may include editing reports or creating new documentation to meet the EU legislation.  2. Understand the options and the EMA consultation process The EMA has published guidance on its website regarding the consultation process (Medical devices | European Medicines Agency (europa.eu)). Read the guidance documents and be sure that you understand the requirements and timelines. The EMA has also made public the companion diagnostic assessment report template. This template includes guidance text for the reviewer on the type of information and data that should be included; this document is a great resource to reference when drafting your SSPs and IFUs. The consultation process includes the following steps: Notification of intent to apply (from notified body) Appointment of Rapporteurs from EMA Pre-submission meeting (optional) Application Submission Question/response period Opinion Rendered 3. Prepare the SSP and IFU with the consultation in mind The purpose of the consultation process for CDx is to confirm the suitability of the device for use with the concerned medicinal product(s), with a focus on the performance and use claims of the device. The only documents submitted to the EMA or competent authority for a CDx consultation are the draft summary of safety and performance (SSP) and draft instructions for use (IFU). These documents must include enough information for the EMA to assess the suitability of the device for use with the medicinal product. A brief summary of performance characteristics that would typically be accepted by the notified body will not be enough information for the EMA to perform the consultation. Be sure to include information regarding scientific validity, analytical performance and clinical performance. Scientific validity should demonstrate the biomarker selection including association of the analyte with clinical condition or physiological state. Summary of the performance evaluation should include both analytical and clinical performance and descriptions of the study design in addition to results. Clinical performance should include a description of the clinical data, description of changes to the device during or after clinical data generation that may impact results, and cut-off point selection rationale. The documents should also include robust discussion of the risk/benefit determination and limitations of the device. Avoid using a single statement that the benefits outweigh the risk and instead include a description and justification for acceptability of the major residual risks that remain for the device. 4. Build extra time into your planning The process for certification of CDx devices is more extensive compared with other devices. This is because of the added steps of the external consultation process in addition to the conformity assessment performed by the notified body. The EMA requires notification of intent to submit a device at least three months in advance of the expected date of submission. The notified body is likely going to perform the bulk of the conformity assessment ahead of submitting a letter of intent. This ensures that the device being put forward for consultation is likely to have a positive outcome for the conformity assessment prior to sending the letter of intent. After the 3-month notification period, the documents are submitted to EMA, and there is a 60-day review period... which may be extended up to 120 days before final recommendation is made. This is in addition to the notified body review and can take anywhere from 8-18 months to complete. Considering these extended timelines, you should waste no time in preparing your files and engaging with a notified body to ensure timely certification of your devices before the transition deadlines. Also consider timelines when making changes  to the device after the initial certification, especially for changes to the claims or the addition of other medicinal products to the intended purpose. These changes will require both notified body review and another consultation with EMA. 5. Collaborate with your notified body Use the resources that are available to you. While the notified body is not allowed to offer consultation regarding your device, they can provide valuable information regarding the CDx process and specific details on the information EMA will be reviewing. Arrange a meeting prior to submitting your technical documentation to understand any additional details that may be needed for your SSP and IFU, but that are not included in the best practice guidance documents or other general IVDR guidance available. This is also a great time to engage the notified body to understand their previous experiences with EMA and receive details on the process that may not be publicly available on the EMA website. If you are looking for more general information on IVDR certification, please review our IVD services page and/or contact us for support on your IVD-related projects. RQM+’s global team of clinical, technical, and top industry experts push the boundaries of excellence and we would be delighted to partner with you. Further reading - How to Obtain CE Marking Under the IVDR Contact RQM+ #### 510(k)-Exempt Devices In the FDA-regulated medical device world, there are 3 classifications for medical devices: Class I, Class II and Class III. The FDA (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/default.htm) provides a rather in-depth overview of how to classify a medical device and the requirements behind each product's classification. What may not be evident, or often discussed in common conversation, is that many Class I and some Class II medical devices are 510(k) exempt. What does 510(k) exempt mean? When a 510(k) submission is required it means that the FDA is requesting notification, along with evidence that the medical device intended to be marketed is safe and effective, prior to a company commercializing its product. In some instances though, the FDA has placed specific medical devices into an "exempt" status. Now, this is not to imply that the FDA does not have requirements for Class I/II 510(k)-exempt devices. The FDA in fact specifies that companies manufacturing 510(k)-exempt devices still follow certain regulations such as: Registration and Listing, Corrections and Removals, Labeling, and GMP's (good manufacturing practices)) (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm051549.htm). Of course, you could get lucky and manufacture 510(k)- and GMP-exempt devices, but that's a separate blog post. Though, it still isn't enough to simply check with the classification database and, if 510(k)-exempt, market your product without care. There are clauses in the regulation that void the 510(k) exemption, most notably if utilizing a new technology in a 510(k)-exempt device, or having a different intended use than what is commonly associated with the 510(k)-exempt device. A great example of the first scenario is how the FDA has looked at some recent design changes in the orthotics industry. Many companies have added electronics or robotics to the orthotics to enhance their usefulness. That shift is viewed as a "new technology" change and would require a 510(k). When beginning your regulatory strategy, or starting your company, the best "first step" would be to visit the following website: (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm), a full listing on the FDA website of 510(k) exempt devices. You could be one of the "lucky few" to see that your path to marketing your device is a bit easier. -MJB #### 8 Strategic Advantages of Outsourcing Audits Staying ahead of compliance and regulatory requirements needs to be a top priority for MedTech companies. Audits are an integral part of maintaining these standards, but can often be seen as stressful and time-consuming events. However, the perspective shifts when these are approached as opportunities for growth and improvement rather than simply compliance checks. This is where the strategy of outsourcing audits comes into play, offering serious advantages. Outsourcing your MedTech audits is not just about ticking boxes; it's about elevating your business practices to a new standard. Below are 8 multifaceted benefits of embracing the outsourcing approach. 1. Deep-Dive Expertise With over two decades of specialization, outsourcing firms like RQM+ bring a level of insight that's hard to replicate in-house. Their auditors are not just ticking off a checklist; they’re identifying areas of risk and helping find opportunities for improvement. Broad industry, function, and educational auditor expertise increase the likelihood of bringing a knowledgeable and creative review. 2. Mentorship and Growth A significant aspect of RQM+ audits is the 80/20 approach, where 80% is thorough auditing and the remaining 20% is dedicated to mentoring. This means not only will the current standards be met, but your team will be guided towards best practices, going from good to great. 3. Cost-Effectiveness An internal auditor is an all-year-round expense, but an outsourced audit is a one-time investment. This offers a clear cost advantage, as you're paying for the expertise only when you need it, allowing your staff to focus on their core duties without disruption. Skilled auditors reduce inefficiencies associated with in-house part-time auditing, including knowing how to relate to all levels and areas of the organization. 4. Time Efficiency Scheduling audits, arranging travel, accommodation, and ensuring auditors are well-prepared can be a huge logistical challenge. Outsourcing removes this burden, freeing up your internal resources and saving valuable time. 5. Continuous Up-to-Date Training Organizations like RQM+ ensure their auditors are continuously trained and up-to-date with the latest regulations and standards, which is a heavy responsibility to maintain in-house, especially for smaller companies. Learn more about how RQM+ provides dedicated resources you can trust. 6. Unbiased Independence Outsourced auditors bring an essential layer of objectivity. Without internal ties, they can provide a clear-eyed assessment of compliance and practices, and are not swayed by internal politics or biases. 7. Assured Compliance With ever-evolving standards and regulations, having a partner that ensures you’re always in step with the latest requirements is invaluable. This means you’re always audit-ready, not just compliant. 🎟️ Relevant upcoming online event: We'll be discussing the importance of being audit ready as part of our presentation and panel discussion on 28 March: Get Ahead of the Crisis: How Your Quality System Can Prevent Negative Impacts on Customers, Patients, and Reputation. Register below. {{cta('a1975037-6c87-4d85-9c2f-6c7b761a21ba')}} 8. Data-Driven Insights and Proprietary Tools Companies like RQM+ don’t just audit; they collect and analyze data across multiple audits to offer insights that can drive strategic business decisions. They also utilize proprietary tools allowing them to increase coverage in the limited time available and provide comprehensive in-process feedback, as well as the audit report itself quickly Choosing to outsource your audits not only allows you to stay ahead of regulators, but can transform what might be a regulatory burden into a strategic advantage. It is an investment in expertise, time, cost-saving, and above all, peace of mind. The importance of choosing a reputable and experienced auditing firm cannot be overstated—it is a choice that could absolutely define the trajectory of your organization. For MedTech firms looking to harness the benefits of outsourced audits, RQM+ offers a partnership that's built on expertise, experience, and a shared vision for excellence. To learn more about how RQM+ can support your auditing needs, contact us. You can visit our audits page for more specifics, too. Our team is ready to be your partner in best practices and continuous improvement. Remember, in MedTech, staying compliant isn't just about avoiding penalties; it's about affirming your commitment to excellence and patient safety. RQM+ can be the ally that helps you uphold these values with confidence and clarity. Again, we encourage you to register for the 28 March event to learn more about the importance of regular internal audits and getting ahead of crises. You'll be able to ask questions live, and all registrants will receive the recording and slides following the session. Sign up here. Keep up to date: Follow RQM+ on LinkedIn Subscribe to our blog Subscribe to the RQM+ Device Advice podcast  #### A Beginner’s Guide to Dynamic Mechanical Analysis Dynamic Mechanical Analysis (DMA) describes a procedure in which the mechanical properties of materials are measured as a function of time, temperature, and frequency. In basic terms, dynamic mechanical analysis involves the application of a stressor on a target such as the reverberation of soundwaves acting upon a sample. The result is expressed as a ratio of stress versus strain when a tremor – or vibratory energy source – is applied to the sample. Alternative experimentation times and varied vibration intensities and frequencies are staged to note the subtle differences in the way the sample reacts. The Purpose of Dynamic Mechanical Analysis Dynamic mechanical analysis is employed to evaluate the various correlations between a sample’s size, structure, and its different thermodynamic or chemical qualities. Our team at RQM+ Lab Services is well-versed in content testing via dynamic mechanical analysis, providing a reliable quantitative basis for definitive conclusions about key sample properties. Simply put, dynamic mechanical analysis allows us to connect critical sample characteristics to tangible effects incurred via thermal and/or mechanical agitation. It resolves many perceived gaps in established testing methodologies by empowering researchers to predict how certain systems will behave under given conditions. This is ideal for product profiling in quality control (QC) and production environments. Dynamic Mechanical Analysis: Procedure The main principle of dynamic mechanical analysis involves the use of an oscillatory energy source, which effuses equally timed vibration frequencies. Peripheral, or variable, vibrations are quenched to ensure the quality of the eventual dataset. During dynamic mechanical analysis, exposure of the sample to the standardized frequencies coming from the vibrations creates changes in the substance’s general structure. The stiffness, softness, and damping are recorded and reported, yielding an overall ‘complex modulus’ which essentially gives a quantifiable rating of the sample’s characteristics. Applications of Dynamic Mechanical Analysis Applicable to a selection of surface materials and components, dynamic mechanical analysis can delve deeply into the configuration of metals, plastics, glasses, and many more. Here we present two potential use scenarios, one focused on materials and the other concerned with properties. Testing Levels of Elasticity, Viscoelasticity or Rigidity Dynamic mechanical analysis is routinely employed to probe specific mechanical properties to determine performance under atypical conditions, such as applied tensile strain or abrupt impacts. RQM+ Lab Services engineers can easily apply dynamic mechanical testing principles to measure the elasticity, viscoelasticity, or rigidity of various sample materials. Investigate Thermal Transitions Dynamic mechanical analysis can be performed in temperature sweep mode to identify glass transitions in samples at sensitivity even greater than differential scanning calorimetry. Dynamic Mechanical Analysis with RQM+ Lab Services This article is only intended to serve as a brief introduction to the principles and applications of dynamic mechanical analysis. If you would like to learn more, there are plenty of case studies and whitepapers available on our site. Or, for any specific questions about dynamic mechanical testing, why not contact a member of the RQM+ Lab Services team today? #### A Comparison of IVDR to FDA IVD Regulatory Submission Requirements The European Union’s new In Vitro Diagnostic Regulation (IVDR) May 2022 implementation date is fast approaching. If you sell IVDs in multiple markets, it may be challenging to determine the differences between the IVD regulations in the U.S., the existing IVDD, and the new IVDR. It’s not surprising that global IVD manufacturers are finding it challenging to keep it all straight. We’re here to help! In this post, RQM+ IVD regulatory experts have created a tool to compare IVD regulations based on regulatory oversight, device classification, post-market surveillance, labeling, and clinical evidence requirements. FDA IVD Regulations The United States Food and Drug Administration (FDA) considers IVDs to be medical devices and they are therefore subject to the relevant regulations for medical devices in the CFR, including the same pre-market and post-market controls. However, IVDs might also be considered biological products that are subject to section 351 of the Public Health Service Act. Determining the various classifications of your IVDs early in the product development process will help inform the appropriate regulatory path.  Advancements in laboratory-developed tests (LDTs) have led to increased scrutiny of these diagnostic tests that aren’t technically considered IVDs at this point. FDA has issued draft guidance and a discussion paper that describes the enforcement discretion for certain regulatory requirements and certain types of LDTs. This naturally creates a gray area for manufacturers and laboratories that develop LDTs when it comes to compliance with IVD regulations in the U.S.      EU IVD Regulations The implementation of IVDR is a major shift in the EU regulatory landscape, and many manufacturers are finding that they aren’t prepared for all it entails. If you are an IVD manufacturer, here are some of the major changes to be aware of as we head toward the IVDR date of application: One of the most significant changes is that the scope has been expanded so many products that were previously self-certified IVDs will need notified body certification under IVDR. The limited number of notified bodies with IVDR designation combined with the sheer volume of IVD companies needing notified body assistance is making it challenging to get on their schedules, especially if you need to change notified bodies.   New risk-based classification rules apply to all IVDs in lieu of the previous list system. Notified body involvement is new to most IVD manufacturers and requires a huge shift in thinking. Don’t underestimate the increased NB scrutiny and stringent documentation that’s required. Discuss any product changes with your notified body and make sure you are clear on what constitutes a significant change that would require the move from IVDD to IVDR sooner than you had planned.  There will be no grandfathering. All IVDs that fall into a category for notified body inspection will need to comply with the IVDR. The application of state of the art to standards is causing some confusion. The expectation is that you are compliant with the current standards. However, not every standard is harmonized. For example, ISO 14971: 2019 hasn’t yet been harmonized, but we are seeing that notified bodies are requiring it because it is considered state of the art.  The person responsible for regulatory compliance (PRRC) is a new requirement under MDR. You must identify qualified employees for this role and document the individuals responsible for regulatory compliance. Economic operator is also a new term in the IVDR and the entities in this role must meet certain requirements. This could be an importer, authorized representative, manufacturer, or distributor. Virtual manufacturing and distribution relationships are common in the IVD industry, resulting in many economic operator agreements and processes to be established for IVDR compliance. These are just a few of the most significant changes IVD manufacturers must be aware of as you transition from IVDD to IVDR. The distinctions between U.S. and EU regulations are outlined in the table below. In Vitro Diagnostic Products: Comparison of IVDR to FDA IVD Requirements Comparison of In Vitro Diagnostic Product Regulations Regulatory Oversight  ClassificationPost-Market Surveillance (PMS)UDI LabelingClinical EvidenceFDA IVDIVDs go through registration and listing, 510(k)s, or PMA submissions with the FDA.**LDT and RUO are handled differently Class I (low risk), Class II (moderate risk), Class III (high risk) Risk-based system  Reactive PMS system—you must report device malfunctions that might result in harmUDI already implemented Clinical evidence is almost always required for class III devices and may be required for Class II based on risk (approx. 10%).Clinical performance testing is required for all IVDs.EU IVDDOnly 10-20% of IVDs were subject to NB oversight; many devices were self-certified, and therefore required minimal NB involvement.General IVD, Self-Testing IVD, List B IVD, List A IVD  Less risk-based than FDA.  Fixed system leaves little room for interpretation. Not directly mentioned in the directive, but it is expected that manufacturers would have a PMS system.Vigilance reporting required.UDI not required Level of clinical evidence required is based on classification.No formal report required.EU IVDR80-90% of IVDs are required to have a certificate; NBs will now have to review the technical files of IVDs based on risk class.Class A (lowest risk), B, C, D (highest risk)Based on rules and risk level for patients and population. International Harmonization utilizes CND codes.PMS requirements clearly defined in regulation.  Requires formal plans and reports.Information is stored in EUDAMED.New requirement for periodic safety update reports (PSURs) for Classes C & D and post-market safety reports (PMSRs) for Classes A & B.Requirement is similar to FDA UDI with a different format.Requires a basic UDI.Information stored in FDA database will be different than info stored in EUDAMED, which requires a more in-depth upload.Performance evidence reports (PERs) are required for analytical performance, clinical performance, and scientific validity. State of the art analysis required. Post-market performance follow-up activities (PMPF) are required and enforced. Key Differences in Regulations As you prepare regulatory submissions in one market, it’s helpful to know how they differ from the other markets where your products are sold. Regulatory Oversight In the U.S., a 510(k) submission demonstrates that your IVD is substantially equivalent to another product on the market. FDA reviews it and responds with a letter indicating whether the device is deemed substantially equivalent. If "cleared" by FDA, it is a one-time process, and the manufacturer isn’t required to demonstrate continuous improvement with state-of-the-art unless there are design changes requiring a new submission. In the EU, IVD manufacturers must now submit to a notified body review of technical documentation. Under IVDD, only a small percentage of devices had regulatory oversight while the rest were self-certified. With the implementation of IVDR, the majority of manufacturers must now submit to technical documentation review by a notified body.  Classification IVD classification in the U.S. and EU aren’t the same, and there is no one-to-one correlation. Manufacturers must follow the risk-based system in each market to classify devices. This is new in the EU because IVDD followed a list system. The scope has expanded under IVDR to include all of the following: reagents, reagent products, calibrators, control materials, kits, instruments, apparatuses, pieces of equipment, software or systems, and specimen receptacles. This system is like the FDA IVD classification because they are both risk-based. Post-Market Surveillance (PMS) U.S. IVD regulations require device malfunctions that could lead to a serious adverse event (death or serious injury) be reported. However, in the EU, this is a challenging area for IVD companies transitioning from IVDD to IVDR. The IVDR requires a much more defined and stringent plan for PMS activities. While having this clarity gives manufacturers a clear path to conformity, it’s causing some challenges for manufacturers with legacy devices.  Labeling and IFU Labeling and instructions for use (IFU) requirements vary in all markets, including the U.S. and EU, and must comply with the relevant regulations. Changes under IVDR include having an NB number and an EU UDI included on labeling. Clinical Evidence  In the U.S., the requirement for clinical evidence for IVDs depends on the classification, but there is no reporting requirement. For the FDA, the emphasis is on the manufacturer’s verification and validation studies to support safety and performance. Under the IVDR, the requirement is for sufficient clinical evidence for your own device and/or an equivalent device if duly justified. This is a big challenge for many manufacturers with legacy devices where sufficient data is not available or compliant with IVDR requirements. The EU requirements also include ongoing reporting. Tips for Efficient IVDR Implementation With the IVDR implementation deadline looming, there’s a lot changing for IVD manufacturers that produce or distribute their devices in the EU, especially for those that were previously allowed to self-certify. Hopefully, you are already well on your way through the transition, but no matter where you are in the process, you are likely ready for some good news. Some of the work you are already doing in other markets or for other products may be applicable to IVDR compliance in the EU. Here are some ways that you can make your hard work go further: If you have filed a 510(k) on your in vitro diagnostic (IVD) device, you may already have some of the documentation and clinical evidence needed for a notified body review. If you have global submissions, you may be able to leverage existing submission data from markets such as Canada and Australia. If you have a quality system certified by a NB, your QMS is well on its way to IVDR compliance. You will need to implement requirements that are new to IVDR and not covered by IVDD and ISO 13485, for example the new requirements for performance evaluation reports and post market surveillance reporting. If you do not have a 13485 certificate, start mapping out your quality system is soon as possible. If you have already implemented UDI per FDA regulations, there are only a couple additional steps needed for compliance in the EU. You may already have the required performance data, which will allow you to reassess and repurpose existing documentation and package it in a way that meets IVDR requirements. Think outside of the box here. This data might have been called something different in the past or perhaps it wasn’t looked at as an input for this deliverable. Ways RQM+ Helps RQM+ has a large team of experts working on multiple IVDR implementations. Whether you need a technical file gap analysis, support with economic operators, or an experienced team to compile clinical and performance data for legacy devices, we have the expertise you need.  We have been involved with IVDR from the beginning and have already received notified body feedback. In fact, some members of our team have been involved in developing guidance documents. From business-balanced strategy to expert implementation, the RQM+ team is here for you.  If you’re not sure how prepared you are, take our IVDR Readiness Assessment to find out.   Read More - Classification for SARS-CoV-2: Adjusting to a Post-Pandemic Reality Under IVDR #### A Quantitative Approach to Benefit-Risk Determination Under the Medical Device Regulation (2017/745) (MDR), demonstrating clinical benefit and quantifying benefit-risk ratios are critical to compliance. A medical device must not be placed on the market if the benefit of the product does not outweigh the risk in a clearly quantified and documented benefit-risk analysis. Qualitative arguments are inherently subjective to some degree – an issue that can be addressed by a quantitative approach. However, despite the importance of benefit-risk ratios in showing conformity with the General Safety and Performance Requirements and placing a product on the market, there is currently little relevant guidance on how to effectively quantify benefit-risk and provide rigorous justification for the conclusions reached. The MDR does not define what an acceptable benefit-risk determination is or discuss how to justify the occurrence of residual risks. As a result, manufacturers are producing purely qualitative benefit-risk analyses, and these often do not meet the required quality level.To enable a quantitative analysis, it is important to begin by defining the relevant and appropriate benefits and risks for the device when used as intended. Improvements in patient health and possible harms need to be specific, and the outcomes must be measurable. Measurable indicators help to quantify the impact of a device, as the indicators can be used to compare a patient’s health before and after treatment, or to compare two different devices. The MDR defines benefit-risk determination as the analysis of all relevant assessments of benefit and risk when the device is used for its intended purpose (See Article 2 (24) for the complete definition). The regulation refers to the benefit-risk ratio as benefit-risk determination and benefit-risk analysis interchangeably. Benefit is defined in Article 2 (53) as the positive impact of a device on the health of an individual, expressed in terms of meaningful, measurable, patient-relevant clinical outcomes, including outcomes related to diagnosis, or a positive impact on patient management or public health. Watch the Webinar: An Intuitive Approach to Quantifying the Benefit-Risk Ratio Clinical Benefits When identifying clinical benefits, the key principle is to approach them from the perspective of the patient or user, or in terms of patient management. Patient-related clinical benefits tend to be discussed mostly in measurable terms of improvements in quality of life, symptom relief, pain relief, reduced rates of re-interventions, improved patient management outcomes such as enhanced diagnosis (for imaging devices) and technical success in the facilitation of index procedures (for surgical accessory-type devices). There may be multiple benefits if the device has more than one positive impact. In sum, the benefit outcomes should tell the story of clinical improvement that the device under evaluation provides to the patient.Clinical benefits should not be considered as synonymous with performance, since they may not necessarily be the same. Performance and benefit can be differentiated as follows: PerformanceThe ability of a device to achieve its intended purposeClinical PerformanceThe ability of a device to achieve its intended purpose, thereby leading to a clinical benefitClinical BenefitThe positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s) Risks ISO 14971 defines risks as the frequency of occurrence of a harm combined with the severity of the harm, the harm being injury or damage to the health of the patient. Risks identified for the device in the clinical evaluation should align with the risk management file and other available risk documentation. The analysis should include the most common harms, including those identified in the instructions for use and those reported in clinical studies using the device. Ideally, only risks that can be reasonably attributed to the device under evaluation would be included in the analysis. However, it is prudent to include any adverse events reported that could reasonably be associated with the use of the device. An illustrative example We applied the principles above to an anonymized wound dressing, AdBan. Using the product’s instructions for use and risk management documentation, we differentiated between: performance outcomes and clinical benefits; and risks attributable to the device versus other adverse advents that could be associated with the product. Intended UseAdBan Wound Dressing provides a moist environment for the management of partial and full thickness wounds.Indications for Use1st and 2nd degree burnsTraumatic woundsSurgical woundsPressure ulcersLeg ulcersDiabetic foot ulcersPerformance OutcomesDuration of adhesionMoisture level of wound environmentReduction of wound sizeBenefitsWound healingRisks Attributed to the DeviceAllergic reactionPeriwound macerationSkin damage on removalOther RisksBleedingInfection Next Steps The next step is to determine overall benefit and risk for the device. There are two key factors in this assessment: magnitude and frequency. Essentially, the following questions need to be answered: MAGNITUDE How great is the benefit? How severe is the risk? FREQUENCY How many people experience this benefit? How many people experience this risk? The rationale for this approach is clearly explained by the guidance document MEDDEV 2.7/1, Rev. 4, A7.2:  “A large benefit, even if experienced by a small population, may be significant enough to outweigh risks, whereas a small benefit may not, unless experienced by a large population of subjects.” Magnitude and Frequency Values Frequency of occurrence may be easy to measure if the Specific and Measurable Outcome (SMO) already expresses the number of patients that experienced the benefit. However, in some cases, it may be necessary to set certain thresholds to then see the number of patients that achieved a specific level of benefit or risk. For example, wound healing could be measured by the reduction in wound size. If a reduction of at least 5 mm2 in the wound surface area is clinically relevant, then this can be the threshold for frequency of occurrence. Determining magnitude values is a more subjective task. Some outcomes may seem to be well suited to a direct measure of magnitude. However, on closer glance, these measures may not necessarily provide clinically relevant information. For example, the decrease in wound surface area (measured in mm2) indicates the magnitude of wound healing and the amount of blood loss (measured in mL) indicates the severity of bleeding. But a 5 mm2 reduction in wound surface area may be much more beneficial than a 5 mL loss of blood is severe. RQM+ has developed a novel method that reduces subjectivity and bias when reviewing magnitude and frequency. This method is used to: assign magnitude and severity values for outcomes which lack these implicit measures; and to establish a normalized scale so that benefit and risk can be directly compared. This method is outlined in more detail in our dedicated white paper: Benefit-Risk Determination: A Quantitative Approach. Calculating Benefit-Risk Ratio Next, by combining the frequency and magnitude measures, each benefit and risk can now be quantified as a single value. Once the benefit and risk values are determined, it is possible to produce a simple benefit-risk ratio. The calculation looks like this: Benefit Value=Frequency x MagnitudeRisk Value=Frequency x SeverityBenefit-Risk ratio=Benefit Value__________________Risk Value This method provides a value for each benefit and each risk; it does not combine all benefits nor all risks to establish one singular benefit value and one singular risk value. This is because a singular value would hide the detail needed for an in-depth analysis. For instance, there is a danger that high-severity risks may be obscured by many low-severity risks, if all risks are simply presented as one value. Determining Acceptability After this process of evaluation, how can manufacturers decide whether their benefit-risk ratios are acceptable? Acceptance criteria should be established before calculating benefit and risk values, so that acceptability can be argued in a clear, rigorous, and unbiased manner. In basic terms, any benefit-risk ratio greater than 1 is favorable (i.e., the benefit value is greater than the risk value). However, the MDR also requires a comparison with devices or therapies that are generally accepted as state of the art. Benefit-risk ratios can therefore be calculated for the state-of-the-art, using the same methodology. This allows for a direct comparison; ideally, the benefit-risk ratio for the device under evaluation will be greater than that of state-of-the-art devices. Acceptance criteria for each device may be unique, to address the specific characteristics of the device and target patient population. For example, if a device has multiple benefits and risks, there will be a collection of benefit-risk ratios to analyze, which makes it more challenging to define criteria. In these instances, a different approach may be needed. One option is to specify that the benefit-risk ratio for at least half of the benefit-risk pairs should be greater for the device under evaluation than for the state of the art. More Resources From RQM+ The steps outlined above present one suggested method of calculating a benefit-risk ratio. RQM+ has successfully implemented this approach to satisfy requests for quantitative benefit-risk analysis from BSI. Our white paper on the topic includes an anonymized real-life example of how we put this approach into practice. This is not to say that other methods are not possible. Ultimately, there must be sound justification for whichever method is selected. Whether you’d like support on calculating your benefit-risk ratios, or an unbiased review of your justification, book a consultation with the team here – we’re here to help! #### Addressing Unmet Needs in Women's Health: Devices for Mental Health Support In the realm of women's health, while significant advancements have been made, there remain critical unmet needs. One area of particular concern is mental health, a topic that unfortunately still carries a stigma. Women often bear a significant mental load related to family and child-rearing, in addition to their professional lives and personal needs. While pharmaceutical options are frequently the primary avenue for treatment, there's a growing recognition of the potential for innovative medical devices and combination products to offer additional support for women's mental well-being. The RQM+ team has worked on devices intended to reduce anxiety and depression, improve insomnia symptoms, and devices to assist and alleviate stress for new mothers in caring for their little ones.   Whether it’s a pharmaceutical product, a medical device, or a novel mental health treatment that doesn’t fit well in either of those buckets, products must go through rigorous regulatory evaluation to demonstrate they are safe and effective. The path to reach that end goal isn’t always obvious, and sometimes, when not done appropriately, can slow down or even prevent health products from reaching patients. Approaching product development and product improvements strategically and early in development, optimizing the development process, obtaining important feedback from Health Authorities, and managing quality and clinical expectations throughout the product lifecycle can accelerate that process, and that is where we at RQM+ shine!  RQM+ has invaluable collective knowledge that our consultants can tap into when working on a project, which essentially means that every client we work with gets the benefit of every other expert in RQM+! It’s important to keep in mind that every medical device must undergo a rigorous process to get on the market. A recent experience sitting in an ICU with a loved one made me contemplate the incredible impact that we make on patients and their families. That ICU room was literally full, floor to ceiling, wall to wall, with medical equipment that was helping keep my loved one alive. I couldn’t help but consider how many people and how much effort it takes to bring each device from an idea in someone’s head, into development, through the regulatory process, and finally to the hospital and connected to someone’s loved one. It wouldn’t be an exaggeration to say that it takes anywhere from 50 people to several hundred people for each device. Each of us that works in the MedTech space are one of the many individuals that enhances the lives of patients and their families every day. RQM+'s Commitment to Women's Health and Innovation As a company that was founded by women, RQM+ supports the full lifecycle of medical devices and combination products for women and for all patients alike. RQM+'s experience in developing comprehensive regulatory strategies, preparing meeting packages for regulatory agencies, and facilitating crucial dialogues can be invaluable for companies seeking to introduce innovative mental health devices for women. By leveraging our collective knowledge and expertise, RQM+ helps clients navigate these uncertainties, potentially accelerating the path to market. #### AI/ML-Enabled Medical Devices: Recognition & Reliance in the UK Slightly overdue, we wanted to highlight one of many discussion points in relation to proposals for international recognition pathways to access the Great Britain (GB) market. The recent update of the FDA’s data on Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices has given us the opportunity to do just that. Note: this is not intended to be an exhaustive look at how to get AI/ML-enabled medical devices onto the US, EU or UK markets. The FDA’s List On 7th August 2024, the U.S. Food and Administration (FDA) updated their list of Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices, indicating that the FDA has authorized 950 AI/ML-enabled medical devices. The list is compiled based on publicly available information and all devices on the list have met the FDA’s applicable premarket requirements. The FDA are transparent that the list is not exhaustive, but the list does serve as a good indicator for this area of technology in the medtech industry.Analysis of the FDA’s data shows a steady increase in the number of AI/ML-enabled medical devices over the last fourteen years (Figure 1). This increase is not surprising, given the general upturn in the use and availability of AI/ML-enabled products and services across all industries. Figure 1. FDA's list of AI/ML-enabled medical devices (y axis represents the count) sorted by the year of the FDA's final decision (x axis) Another unsurprising element is the clinical areas in which the devices fall. Three quarters (76%) of the devices on the FDA’s list come under the Radiology panel (Figure 2), with the Cardiovascular panel taking 10% of devices on the list and 3rd place taken by the Neurology panel with only 4% of the devices. When looking at the Product Codes cited for each device on the FDA’s list, the top 10 Product Codes represent two-thirds of the list contents with LLZ and QIH taking nearly 30% of the overall total. Given the spread of devices by panel (Figure 2), there are no surprises that the top 10 codes all sit under the Radiology panel and are classified as Class 2 by the FDA (Table 1). Figure 2. AI/ML-enabled medical devices (y axis represents the count and cumulative %) sorted by FDA's review panel (lead) Table 1.Top 10 Product Codes from the FDA's list Product CodeDevice NameDevice ClassRegulation No.TPLC LinkLLZsystem, image processing, radiological2892.2050LLZQIHautomated radiological image processing software2892.2050QIHJAKsystem, x-ray, tomography, computed2892.1750JAKIYNsystem, imaging, pulsed doppler, ultrasonic2892.1550IYNLNHsystem, nuclear magnetic resonance imaging2892.1000LNHQASradiological computer-assisted triage and notification software2892.2080QASQFMradiological computer-assisted prioritization software for lesion …2892.2080QFMQKBradiological image processing software for radiation therapy2892.2050QKBMUJsystem, planning, radiation therapy treatment2892.5050MUJMYNanalyzer, medical image2892.2070MYN Digging further into the top 10 Product Codes on the FDA’s list (n=634, 66.7%), there was one device that went through the De Novo pathway (Product Code QAS) and two devices that went through the Premarket Approval (PMA) pathway (Product Code MYN). All of the rest of the devices (n=633) went through the 510(k) pathway, i.e. the subject device successfully demonstrated substantial equivalence with a predicate device (see BOX 1). As far as this author is aware, there is no current guidance from the FDA regarding how to compare the technical characteristics of AI/ML-enabled medical devices in order to demonstrate substantial equivalence. Examples of 510(k) summaries viewed (of devices on the FDA’s list) did compare inputs, user interfaces, image processing capabilities and operating systems but few revealed details of the training of the ML-model or its subsequent testing. What is Substantial Equivalence? A 510(k) requires demonstration of substantial equivalence to another legally U.S. marketed device. A device is substantially equivalent if, in comparison to a predicate it: has the same intended use as the predicate; and has the same technological characteristics as the predicate; or has the same intended use as the predicate; and has different technological characteristics and does not raise different questions of safety and effectiveness; and the information submitted to FDA demonstrates that the device is as safe and effective as the legally marketed device. SOURCE: FDA Premarket Notification 510(k) The FDA’s guidance for the content of premarket submissions for device software functions does outline AI/ML specific considerations to be included in the device description, along with key information to be included in both the Basic and Enhanced documentation levels. There is however no clear discussion on how substantial equivalence needs to be demonstrated for an AI/ML-enabled medical device in terms of the technological characteristics, especially where the details of the training and test data are not always publicly available to enable a comparison of similarities and differences that could affect performance and safety. It is a logical conclusion that these trends will continue in some form in the short to medium term. AI/ML-enabled devices will still predominantly be intended for radiological purposes and the majority will be incremental iterations on previous versions to enable access to the US market via the 510(k) pathway. Where is this going you may ask? Global Collaboration and Harmonisation The FDA have worked closely with Health Canada and the UK’s MHRA to develop good practice guidelines for AI/ML-enabled medical devices on the subjects of good machine learning practices, predetermined change control plans and transparency. These three regulatory authorities clearly share, at some level, a common vision on the best practices related to the increasing use of artificial intelligence, and more likely machine learning, in medical devices. But despite these previous collaborations and presumably continuing collaborations on this topic, there is a slight wrinkle to address; one that shines a light on the apparently different approaches to conformity assessments between two of those national competent authorities. Crossing the Atlantic In May 2024 the MHRA announced their intentions for an international recognition policy for medical devices. This policy was published in the context of the MHRA’s work on the future regulatory framework for medical devices in the UK. The policy is built upon a combination of recognition (e.g. acceptance of a decision of another regulatory authority) and reliance (e.g. taking account of an assessment performed by another regulatory authority when performing your own assessment) (See Figure 3, and also WHO TRS 1033 Annex 10 for further information on good practices for reliance in regulation). Reliance and recognition can represent a ‘smarter’ approach to regulatory conformity assessments and market access, with the MHRA stating that reliance can result in “more predictable, faster approvals to improve access to quality-assured medical devices for patients”.  Figure 3. Figure taken from the WHO TRS 1033 Annex 10: Good reliance practices in the regulation of medical products. The MHRA’s statement of intent logically presents the use of reliance as a method to help mitigate resource constraints, by reducing duplication of effort in relation to performing conformity assessments for devices that have already been ‘approved’ for use by trusted regulatory authorities, and thus enable the MHRA’s resources to be directed towards more innovative products (see Box 2). To offer a level of control and reduce uncertainty, the MHRA, in their statement of intent, have identified four comparable regulator countries (CRCs), which includes the United States of America, specifically the FDA. Devices that have achieved market access in one or more of these countries/regions will be eligible for this proposed pathway into the GB market. MHRA’s Consultation This approach was part of the 2021 consultation by the MHRA, as part of the questions on Domestic Assurance. There were nearly 900 responses to the MHRA’s consultation in 2021, with just over 200 responses on the Domestic Assurance questions relating to MDSAP but only 66 responses to the specific question seeking opinion on whether the MHRA should allow routes to market that leverage approvals from other countries. One may consider that AI/ML-enabled medical devices fall into innovative product territory. The FDA’s list says otherwise. Of the 950 devices on their list, 97% were cleared through the 510(k) pathway, meaning that they were substantially equivalent to a predicate. More incremental improvement than innovation some might say. A crude review of some of the 2024 clearance decisions (covering product codes LLZ and QIH, all under regulation 21 CFR 892.2050) showed that those clearances were based on multiple layers of equivalence (i.e. equivalent with a predicate that was equivalent with a predicate and so on). In some cases, the predicates were previous generations of the manufacturer’s own device, in other cases the predicates were from various other manufacturers, and in some cases it was a mix of these two. It is this approach to equivalence (i.e. multiple layers of ‘piggybacking’ on a predicate), the potential for ‘product creep’ and the paucity of device-specific clinical data that is typically viewed with concern in the EU and the UK. This in part explains the stricter requirements around how to demonstrate equivalence in the EU MDR 2014/745 (compared to the requirements of the earlier Directives) and the MHRA’s stated intention to take the UK’s requirements for equivalence “beyond the equivalence requirements in the EU MDR” (UK Government response to consultation on the future regulation of medical devices in the United Kingdom, 2021). In its current guise, the MHRA’s statement of intent has a list of nine exclusions, one of which is “SaMD (including AIaMD) products approved via a route which relies on equivalence to a predicate (US 510(k))”. That means the bulk of the FDA’s list of AI/ML-enabled medical devices are covered by this exclusion. For the purposes of this discussion there are two things that can be inferred from the MHRA’s list of exclusions: The MHRA are not fans of equivalence; Software as a medical device (SaMD), including AI/ML-enabled medical devices (MHRA refer to this as AIaMD) may be viewed more cautiously by the MHRA compared to the FDA. So 924 of the AI/ML-enabled medical devices on the FDA’s list would be excluded from using the proposed international recognition pathway to access the Great Britain market. It’s not that they would fall into one of the three reliance pathways rather than the outright recognition pathway (which is only really available to lower risk devices such as Class I CE marked medical devices from the EU); but these 924 devices would be excluded from the whole recognition pathway and therefore would need to follow an alternative path to the GB (see examples in Box 3). The MHRA’s exclusion specifically calls out the US 510(k), but it remains to be seen how the MHRA would view an AI/ML-enabled medical device that attained a CE mark by using equivalence as part of its clinical evidence strategy. More specifically, if the responsibility of the assessments for the four recognition and reliance pathways eventually sits with the UK Approved Bodies, how would the MHRA even know the strategies used by the device manufacturers to support the safety and performance of their device in order to obtain the CE mark. Examples Under the current proposal, manufacturers of AI/ML-enabled medical devices cleared for the US market via a 510(k) could access the GB market via one of the following routes: i) UKCA conformity assessment process but there is currently a limited choice of UK Approved Bodies and uncertainty over when the future UK regulations will come into force and what they will contain, especially with regards to AI/ML-enabled medical devices. ii) CE marking for the EU market, where safety and performance data for the subject device would be reviewed by a EU Notified Body, after which the device could then utilise the CE mark to access the GB market. The caveat here is the uncertainty of how Regulation 2024/1689 (AKA the AI Act) will be. The proposed policy, and the exclusion of AI/ML-enabled devices cleared via the 510(k) path in the US, does not currently account for the different shades of 510(k) pathways, especially the requirement for special controls for specific product codes. These special controls can require very specific comparative testing and clinical data to be included within the 510(k) submission. Evidence packages of this nature, and the subsequent clearance based on that evidence, may be seen more favourably than the usual perception of devices cleared by claiming substantial equivalence to a predicate. Perhaps there could be scope for the exclusions to be modified with time. There is also no mention of the option for having stricter requirements for post-market surveillance (and subsequent reporting) as a proportionate measure that could enable these AI/ML-enabled medical devices to access the market via the recognition pathway but subsequently be monitored more closely once on the market. Final thoughts Medical devices that incorporate artificial intelligence or machine learning are on the rise. The data from the FDA indicates that the increase in these devices is not really a technological revolution, but more like quick-fire, iterative, evolution based upon existing devices. To push those devices down a more (at least in perception) burdensome conformity assessment route to access the GB market, may be an obstacle that device manufacturers choose to avoid. It is possible that the current exploratory work on the international recognition policy may highlight some of these issues, or that the MHRA’s AI Airlock identifies elements of the market access pathway that could be improved. As much is made of regulatory harmonisation and alignment, it still seems that there are oddities to be resolved even between key collaborators in the harmonisation process. Further Reading FDA Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices FDA Artificial Intelligence and Machine Learning Software as a Medical Device Action Plan (January 2021) FDA Content of Premarket Submissions for Device Software Functions (14 June 2023) FDA Premarket Notification 510(k) FDA Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) - Discussion Paper and Request for Feedback (2 April 2019) FDA Software as a Medical Device (SAMD): Clinical Evaluation (adoption of IMDRF/SaMD WG/N41FINAL:2017) (8 December 2017) FDA Special Considerations for 510(k)s: Software FDA Technical Performance Assessment of Quantitative Imaging in Radiological Device Premarket Submissions (16 June 2022) FDA/MHRA/Health Canada Good Machine Learning Practice for Medical Device Development: Guiding Principles FDA/MHRA/Health Canada Predetermined Change Control Plans for Machine Learning-Enabled Medical Devices: Guiding Principles IMDRF consultation on Good machine learning practice for medical device development - Guiding Principles (Closed 30 Aug 2024) IMDRF consultation on Medical Device Software: Considerations for Device and Risk Characterization (Closed 2 May 2024) MDCG 2020-1 Guidance on clinical evaluation (MDR) / Performance evaluation (IVDR) of medical device software (March 2020) MHRA AI Airlock: the regulatory sandbox for AIaMD (last updated 21 August 2024) MHRA Crafting an intended purpose in the context of software as a medical device (SaMD) (22 March 2023) MHRA Medical device stand-alone software including apps (including IVDMDs) (v1.10f) MHRA’s Statement of policy intent: international recognition of medical devices Transparency for Machine Learning-Enabled Medical Devices: Guiding Principles WHO TRS 1033 Annex 10 Good reliance practices in the regulation of medical products. Wires to AI: The Regulatory Landscape of Neurological Devices #### Ambulatory Cardiac Monitoring Devices: Is Your Evidence Compelling or Just Adequate? Regulatory clearance for an ambulatory cardiac monitoring device is not the same thing as market traction. The evidence that satisfies an ambulatory ECG (AECG) device submission (signal quality, noise floor, analyzable time, patient compliance) answers a different set of questions than the ones cardiologists and payers are actually asking. The gap between evidence that clears the regulatory bar and evidence that changes clinical practice is where too many cardiovascular clinical trial management programs fall short. Closing it cannot be accomplished by simply doing more studies. It’s a matter of designing the right studies. What Regulatory Requires vs What the Market Demands AECG regulatory performance benchmarks focus on device signal acquisition and patient compliance. These are necessary and the standard is clear. But patient compliance alone will not persuade a cardiologist to change their practice, nor will it move a payer. Cardiologists want to see: Diagnostic yield by indication and monitoring duration Time to detection of clinically actionable arrhythmias Evidence of additive benefit over shorter or less capable monitoring alternatives Payers want economic benefit: Can the device reduce hospital stays? Can it support safely discharging post-procedure patients earlier? Can it reduce emergency department visits in syncope populations? Those questions demand a different evidence strategy than the one that drives clearance, and teams that don’t plan for both up-front are likely to discover that gap at the worst possible time. Why Detection Rates Are No Longer Enough The field broadly accepts that a longer ambulatory cardiac monitoring duration detects more arrhythmias. But whether more detection leads to better outcomes is still actively debated, and clinicians are well aware of it. The more important question now — and the one that guidelines and key opinion leaders are increasingly focused on — is not total detection rate but two more specific measures: Time to detection and arrhythmic burden. Time to detection is population-dependent in ways that matter enormously for study design. For post-transcatheter aortic valve replacement (TAVR) patients, AV block risk was historically thought to peak in the first 48 hours. Ambulatory monitoring studies, however, have shown clinically significant events continuing through 6 to 7 days post-procedure, with current guidance recommending continuous ambulatory monitoring for 7 to 30 days, depending on the conduction pattern observed.¹ For syncope patients, the diagnostic yield of ambulatory monitoring increases substantially with monitoring duration, with longer periods capturing arrhythmic events that shorter Holter-equivalent windows miss entirely.² Burden matters because the pattern of an arrhythmia drives clinical decisions. High AF burden versus low-density paroxysmal AF, continuous versus infrequent episodes: These distinctions inform risk stratification and treatment decisions in a way that a simple positive detection rate does not.³ Sponsors who report burden alongside detection rates are building evidence that guideline committees can act on. Those who don’t are not reporting their most persuasive data. Fit for Purpose Means Population Specific Ambulatory cardiac monitoring evidence does not transfer across indications. A 14-day patch monitor studied in post-stroke patients is generating a different evidence base than one studied post-TAVR or in unexplained syncope. The 2024 ACC Expert Consensus on Arrhythmia Monitoring After Stroke recommends at least 14 days of monitoring for patients with ischemic stroke from presumed small- or large-vessel disease, with atrial fibrillation (AF) episodes of 5 minutes or more triggering anticoagulation decisions. Monitoring this threshold requires both duration and detection sensitivity to be fit for that clinical context.³ Applying the same study parameters across a different population produces evidence that satisfies neither the specific indication nor the broader coverage question. This is also where payer scrutiny is likely to be most active. Coverage decisions for near-real-time monitoring are facing more pushback for broader populations. The burden of proof is on the manufacturer to demonstrate that near-real-time capability produces superior patient benefit over standard mail-in monitoring for the specific indication being claimed. That body of evidence is still being built for multiple device categories. The Adequate vs Compelling Self-Check Adequate evidence demonstrates consistent signal with high analyzable time (typically well above 90%) and an acceptable safety profile. Compelling evidence does that, but it then goes further. Before finalizing a study design, teams should ask: Does the evidence show the benefit of the prescribed monitoring duration over a shorter or less capable alternative, in a clearly defined population? Is time to detection reported along with total detection rates? Is arrhythmic (e.g., AF or VT) burden quantified and included in the study outputs? Does the evidence match what current clinical practice guidelines, key opinion leaders, and payer coverage decisions are prioritizing? Teams that don’t report time to detection and arrhythmic burden are leaving the most persuasive elements of their evidence behind. The move toward AF burden as a predictor of stroke risk and ablation failure is well underway at major cardiovascular conferences, and sponsors whose study designs don’t account for it are already behind.4 Build Evidence That Earns Confidence Ready to build cardiovascular clinical trial evidence that holds up beyond the regulatory submission? Connect with RQM+’s clinical specialists to stress test your evidence strategy before your study design is finalized.  Frequently Asked Questions What endpoints should ambulatory cardiac monitoring studies include beyond detection rates? Diagnostic yield and analyzable time address the regulatory bar, but time to detection and arrhythmic burden are what payers and guideline bodies increasingly require to support coverage decisions and practice change. Whether it’s AF burden, NSVT burden, or paroxysmal arrhythmia frequency, burden more directly informs treatment decisions than a total detection rate, and it is becoming a standard reporting expectation at major cardiovascular conferences. How does evidence strategy differ across monitoring indications like post-TAVR, syncope, and post-stroke? Each indication has a different clinically appropriate monitoring duration and a different primary arrhythmia of concern. Post-TAVR programs need to account for AV block risk extending days beyond the procedural window.¹ Syncope populations show meaningful incremental detection with longer monitoring periods.² Post-stroke recommendations are driven by AF detection thresholds and etiology-specific monitoring duration guidance.³ Sponsors who apply a single study design across indications typically end up with evidence that is suboptimal for regulatory clearance and insufficient for guideline inclusion in any of them. Why do payers push back on near-real-time continuous monitoring coverage even when the device has regulatory clearance? Clearance establishes that a device performs its intended function. Coverage requires evidence that the device’s function produces measurable clinical or economic benefit in the target population. Near-real-time continuous alerts provide clear value where delayed detection has documented clinical consequences. For broader populations, payers expect manufacturers to demonstrate superior benefit over the less costly monitoring alternative, and that comparison has not yet been made for every indication where near-real-time monitoring is being sought. References Glikson, M., Nielsen, J., Kronborg, M., et al. (2021). 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. European Heart Journal, 42(35), 3427–3520. https://doi.org/10.1093/eurheartj/ehab364 Shen, W.K., Sheldon, R.S., Benditt, D.G., et al. (2017). 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope. Circulation, 136(5), e60–e122. https://www.ahajournals.org/doi/10.1161/cir.0000000000000499 Spooner, M., Messé, S., Chaturvedi, S., et al. (2024). 2024 ACC Expert Consensus Decision Pathway on Practical Approaches for Arrhythmia Monitoring After Stroke. Journal of the American College of Cardiology. https://www.jacc.org/doi/10.1016/j.jacc.2024.10.100 Van Gelder, I.C., Rienstra, M., Bunting, K.V., et al. (2024). 2024 ESC Guidelines for the management of atrial fibrillation. European Heart Journal, 45(36), 3314–3414. https://doi.org/10.1093/eurheartj/ehae176 #### An Overview of Chemical Characterization of Medical Devices Medical devices comprise any number of materials, typically a combination of metal, ceramic, and/or polymers. The exact composition depends primarily on the desired functionality. A tongue depressor, for example, is one of the simplest devices in a medical practitioner’s toolkit, typically comprising a single component–thus a single material. At the other end of the complexity scale would be a critical, multi-functional high-tech device, such as an artificial pancreas system. High-functionality medical devices typically require greater design complexity. Part of the cost therein is additional scrutiny. Each material used in device construction undergoes processing and fabrication–potentially also synthesis–that impacts biostability and compatibility. These factors are vital in ensuring suitability. Robust chemical characterization is, thus, essential for ensuring patient safety and regulatory compliance. It involves identifying and quantifying chemical constituents to detect potential toxicological risks. This comprehensive analysis aids in mitigating adverse reactions, validating manufacturing processes, and enhancing the overall reliability and efficacy of medical devices. Key Components of Chemical Characterization ISO 10993 Standards ISO 10993 is a series of international standards providing guidelines for the biological evaluation of medical devices. These standards are essential for ensuring that medical devices are safe for use. Key aspects of ISO 10993 include: Biocompatibility Testing: Ensuring that materials used in medical devices do not pose risks to human health. Extractables and Leachables Testing: Evaluating how much and how quickly compounds can be transferred from the device into the environment or the human body. Extractables and Leachables (E&L) Testing E&L testing is at the heart of chemical characterization. Extractables are compounds that can be extracted from a device under exaggerated conditions, while leachables migrate into the body under normal usage conditions. These tests help determine the level below which a substance is not expected to pose a risk to human health (threshold of toxicological concern) and  the potential for chemical release under extreme conditions to ensure safety margins. Toxicological Risk Assessment A comprehensive toxicological risk assessment involves several steps: Hazard Identification: Identifying any compounds that may pose a risk, including their nature (e.g., carcinogenic or neurotoxic). Dose-Response Assessment: Determining the levels of exposure that could cause a toxic response. Exposure Assessment: Evaluating the population that might be exposed to the chemical. Risk Characterization: Understanding the likelihood and severity of potential hazards. Biological Equivalence In the EU, establishing biological equivalence is essential for leveraging existing clinical data from equivalent devices. This involves demonstrating that devices: Use the same materials Are in contact with the same tissues or fluids Have similar release characteristics of substances. Chemical characterization plays a crucial role in this process by providing a baseline for comparing devices. Regulatory Compliance and Expert Involvement Adhering to ISO 10993 standards and involving expert testers are crucial for interpreting biological evaluation data and designing necessary testing protocols. This helps in waiving certain tests when existing data is available and ensures new tests are performed as required. Challenges and Considerations Chemical characterization is not without its challenges. One significant challenge associated with chemical characterization is the complexity of accurately identifying and quantifying the wide range of potential extractables and leachables. This requires advanced analytical techniques and expertise in interpreting the data. Moreover, the evolving nature of regulatory requirements necessitates continuous updates to testing protocols and methodologies. Furthermore, there is a growing need for more refined toxicological risk assessments that consider the latest scientific developments and emerging health concerns. This includes understanding the long-term effects of low-level exposures to certain chemicals and the potential for cumulative effects from multiple sources. Explore RQM+'s Expertise in Chemical Characterization At RQM+, we specialize in ensuring the safety and compliance of medical devices through rigorous chemical characterization. Our team of experts is equipped with the latest analytical techniques and extensive regulatory knowledge to help you navigate the complexities of ISO 10993 standards and toxicological risk assessments. Why Choose RQM+? Unmatched Expertise: Our experienced professionals have deep knowledge in biocompatibility testing, extractables and leachables (E&L) testing, and toxicological risk assessments. Comprehensive Services: From hazard identification to risk characterization, we offer a full suite of services to ensure your medical devices meet regulatory requirements. Regulatory Insight: Stay ahead with our up-to-date understanding of evolving regulatory standards and best practices in chemical characterization. Learn More About Our Services for Chemical Characterization Chemical characterization testing for medical devices Using chemical characterization to achieve biological equivalence Understanding ISO 10993 standards Partner with RQM+ to ensure the safety and compliance of your medical devices. Visit our website to discover more about our lab services and how we can support your chemical characterization needs. References Chandrasekar V, Isayeva I, Liu J, Nahan K, Oktem B, Shin H, Sussman E, Wickramasekara S, Zheng J. Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices. ACS Biomaterials Science & Engineering. 2022;8(3):939-963. doi:10.1021/acsbiomaterials.1c01119. Materials and Chemical Characterization Program: Research on the Materials and Chemical Characterization of Medical Devices. U.S. Food & Drug Administration. https://www.fda.gov/medical-devices/medical-device-regulatory-science-research-programs-conducted-osel/materials-and-chemical-characterization-program-research-materials-and-chemical-characterization. Updated 30/01/2023. Accessed 30th July 2024. Mark Anderson Jordi, Smriti Khera, Kevin Roland, Liuwei Jiang, Paige Solomon, Jenny Nelson, Syed Salman Lateef, James Woods, Leland Martin, Samantha Martin, Frankie Aiello, Nina Chen. Qualitative assessment of extractables from single-use components and the impact of reference standard selection. Journal of Pharmaceutical and Biomedical Analysis. Volume 150. 2018. https://doi.org/10.1016/j.jpba.2017.12.029. #### An Overview of Toxicological Risk Assessments What is a Toxicological Risk? Toxicological risk measures the probability of an adverse effect being caused by a given compound. This covers effects such as skin irritation from topical treatments to more serious risks such as a material being carcinogenetic or fatal if ingested. The severity and type of toxicological risk depend somewhat on how the compound will be used. Compounds used in devices that will be used under the skin have stricter toxicological risk assessment as the toxicological risk is more significant for small concentrations of compounds for internal use. A toxicological risk assessment should describe all aspects of toxicological risk, including safe exposure limits in concentration and time. Performing a complete toxicological risk assessment is critical in approving any new medical device and can be time-consuming and costly if not handled with expert care.1 The 4 Steps in Toxicological Risk Assessment There are four main steps in toxicological risk assessment.2 The first is Hazard Identification. Hazard Identification in a toxicological risk assessment means identifying any compounds that may pose a risk, no matter how slight. Part of the hazard identification process in a toxicological risk assessment is also identifying the nature of the hazard – is it carcinogenic, neurotoxic, or flammable? The nature of the hazards is essential as, depending on the device’s intended use, different risks need to be screened for. Next in the toxicological risk assessment is the dose-response assessment. This is about understanding what compound level could cause a toxic response and what conditions may be necessary to achieve this. The exposure assessment involves looking at the population that might be exposed to the chemical undergoing the toxicological risk assessment. Many medical devices only pose a local risk to the individual patient, but others could potentially come into contact with other people who may also be vulnerable. The final stage of the toxicological risk assessment is risk characterization. This stage is about understanding how likely particular hazards are to occur and how severe the effect of a potential hazard could be. The risk characterization is where the results of the toxicological risk assessment are expressed and any potential uncertainties in the risks or estimates of the magnitude of risk. Critical Applications of Toxicological Risk Assessments Toxicological risk assessments are an essential part of developing any new medical treatment or device. Whether new or existing materials are being used, compounds must be evaluated to see whether existing safety data can be used instead of further testing. To find a partner to guide you through the toxicological risk assessment process, contact RQM+ Lab Services. RQM+ Lab Services have extensive experience in biological safety guidance and toxicological risk assessments and can help you navigate the testing process. To find out how bringing in an expert partner like RQM+ Lab Services can help you accelerate the creation of your essential toxicological risk assessments, get in touch to find out more about the range of testing services and expert advice that RQM+ Lab Services can offer. FDA (2022) ISO 10993-1, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and, accessed May 2022 National Research Council (US) Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology. Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment. Washington (DC): National Academies Press (US); 2007. C, Overview of Risk Assessment. https://www.ncbi.nlm.nih.gov/books/NBK10201/ #### Approved, Covered, Adopted: Why Reimbursement Strategy Has to Come First  Jaishankar Kutty, Ph.D., VP of Regulatory, Reimbursement, and Access, Cardiovascular Center of Excellence, RQM+ I have spent most of my career at the intersection of clinical evidence, regulatory science, and reimbursement reality. I have watched devices with genuinely compelling science move through pivotal trials, achieve approval, and then stall because the commercial infrastructure to support adoption was never built into the program design. At LSI USA 2026, I presented a framework I have been developing over years of working through CMS coverage decisions, IDE studies, national coverage determinations, and payer advisory boards.¹ The core argument is simple: Most reimbursement outcomes are decided before approval, not after. The evidence design choices you make at the protocol stage determine whether your device ends up just being approved, or being approved, covered, and adopted. The Most Dangerous Word in MedTech “Eventually.” Reimbursement … eventually. CPT code … eventually. Coverage … eventually. Adoption … eventually. I have seen this word appear in business plans, investor decks, and board presentations more times than I can count. What it tells me is that the team has achieved regulatory clarity and commercial ambiguity at the same time. The approval is real, but the revenue is theoretical. And the path between them is treated as something to figure out later. The problem with that approach is that “later” is exactly when you have the least leverage to fix it. The three forces that determine whether a device actually reaches patients are regulatory, clinical, and economic. Regulators determine whether a device can exist Clinicians determine who will benefit Payers determine whether it will be used These are simultaneous constraints on the same study design, not sequential steps. A trial built to satisfy only one of them is a trial that leaves the other two to chance. Evidence That Wins Twice The devices that achieve genuine commercial success share a pattern. The evidence was designed to satisfy regulatory reviewers and payer decision-makers with the same data. The patient population looked like the real-world population the system will actually reimburse, not a carefully curated, anatomically pristine cohort optimized for clean Kaplan-Meier curves. The primary endpoints demonstrated patient-centered benefit and system value, with technical metrics in a supporting role. And real-world evidence was built into the program architecture from the start, not retrofitted after approval when the coverage question came to the forefront.² The devices that stall share a different pattern. Evidence is only sufficient for clearance. The value story is vague or absent. No credible plan exists for permanent coverage. These outcomes are rarely surprising in hindsight. The signals were there in the protocol design because evidence design determines commercial destiny. The Hospital Economics Test There is a layer of this problem that does not receive enough attention, and that layer is hospital economics. Even when a device achieves coverage, adoption can stall because the economics punish the institutions being asked to use it. Two structural forces can quietly kill adoption at the hospital level: Payment misalignment means that if a hospital loses money on every case, innovation gets rationed regardless of clinical benefit. Workflow burden means that unpaid clinician time accumulates as resistance, even when no one says so directly. Before a hospital adopts a new technology, the real questions being asked are whether it improves outcomes, reduces cost or risk, and fits the payment model. Hospitals do not reject innovation. They reject negative margin. A reimbursement strategy that stops at coverage without modeling the hospital economics of adoption is only half a strategy. Post-Market Evidence Is the Second Approval The program does not end at approval. Post-market evidence is how the system updates its belief about your device, and that updating process shapes coverage renewal, indication expansion, and pricing defense over the long term.³ Post-market evidence either compounds the value of your approval or steadily erodes it. Teams that treat post-market surveillance as a compliance obligation rather than a strategic asset are leaving the most durable part of their commercial story unwritten. The practical implication is that PMCF strategy, registry architecture, and claims linkage planning should not be deferred until after approval. They need to be designed alongside the pivotal evidence plan, because the payer questions that arise post-approval are predictable, and the ability to answer them depends on data that have to be collected prospectively.² A Self-Check Before You Lock the Protocol Before your pivotal trial begins, four questions are worth sitting with: Are the patients in your study the patients the system will actually reimburse? Are you comparing against what payers already fund? Will your endpoints demonstrate system value, not just biological effect? Will your evidence survive payer scrutiny three years after approval? If any of those questions produce hesitation, there’s still time to respond. Once the trial is locked, the runway is committed, and the market has formed an impression of your device, the room to maneuver shrinks considerably. Reimbursement problems designed into the protocol have an obvious solution. Design the protocol differently — before the evidence is locked, not after.4 Frequently Asked Questions Why isn’t regulatory approval enough to drive adoption and reimbursement? Regulatory approval establishes that a device is safe and effective for its intended use. Coverage decisions require evidence that the device improves outcomes and delivers value in the real-world population a payer is responsible for, which is often broader, older, and more complex than the population studied in a pivotal trial. These are different evidentiary standards, and a program designed to satisfy only one of them will routinely fail the other. What does a reimbursement-ready trial design actually look like? It starts with a patient population that reflects real-world complexity rather than optimized study conditions. It includes primary endpoints that capture patient-centered outcomes and system impact alongside technical performance metrics. It has a comparator arm built around what payers already fund. And it incorporates a post-market evidence architecture (registry participation, claims linkage, PMCF strategy) designed from the start rather than retrofitted after approval. When is the right time to bring reimbursement strategy into the development process? Early feasibility is not too early. The protocol decisions made before a single patient is enrolled determine whether the evidence can answer the coverage questions that will arise years later. By the time a pivotal trial is locked, and the device is approaching approval, the most consequential reimbursement strategy decisions have already been made — often without anyone in the room asking the payer questions. References  1 Kutty, J. (2026). Approved. Covered. Adopted. Presented at LSI USA 2026, Waldorf Astoria Monarch Beach Resort, Dana Point, California. March 17, 2026. 2 Centers for Medicare & Medicaid Services. Coverage with Evidence Development. Accessed 2025. https://www.cms.gov/medicare/coverage/evidence 3 Centers for Medicare & Medicaid Services. Medicare Coverage of Investigational Device Exemption (IDE) Studies. Accessed 2025. https://www.cms.gov/medicare/coverage/investigational-device-exemption-ide-studies 4 Centers for Medicare & Medicaid Services. Final Notice — Transitional Coverage for Emerging Technologies (CMS-3421-FN). 2024. https://www.cms.gov/newsroom/fact-sheets/final-notice-transitional-coverage-emerging-technologies-cms-3421-fn  #### Are High-Quality PMCF Surveys Enough for High-Risk Devices? Under the EU Medical Device Regulation (MDR), post-market clinical follow-up (PMCF) plays a key part in maintaining evidence of safety and performance after a device is placed on the market. For high-risk devices (such as Class III implants or novel technologies) manufacturers must continuously collect clinical data to confirm that benefits outweigh risks. One increasingly common approach is the PMCF survey, which gathers real-world evidence through structured questionnaires distributed to clinicians or patients. Yet, the question remains: Are high-quality PMCF surveys alone sufficient for high-risk devices? The MDR has raised the bar for clinical evidence, eliminating grandfathering of legacy devices and placing greater emphasis on real-world performance. While PMCF surveys are efficient and scalable for high-risk devices, their adequacy depends on a robust design and sophisticated strategy in the context of a tailored ensemble of evidence. Defining “High-Quality” PMCF Surveys Not all surveys are created equal. According to MDCG 2020-6 Appendix III, post-market data sources are ranked by evidentiary strength. High-quality PMCF user surveys are considered Level 4 evidence (a meaningful source of clinical data) while basic “user feedback” or satisfaction questionnaires fall to Level 8 evidence. A high-quality PMCF survey typically features: A prospective, pre-defined design aligned with clinical endpoints. Targeted respondents (qualified clinicians or end-users) with case-level data rather than general opinions. Scientific validity, including clear objectives, appropriate sampling, and statistical planning. Bias minimization, achieved through structured data collection and documentation. Collection of anonymous responses without protected, personally-identifying health information.  When properly designed, high-quality surveys approach the rigor of observational studies. For instance, collecting physician-reported outcomes per patient case reduces recall bias and improves traceability, which are key factors regulators assess when evaluating the level of PMCF evidence. Regulatory Expectations for High-Risk Devices For Class III and IIb high-risk devices, the MDR mandates a high level of clinical evidence. Article 61(1) requires manufacturers to justify that their clinical evidence is appropriate given the device’s risk and novelty on the market. Regulators and Notified Bodies generally expect robust clinical investigations (Level 1–2 evidence) for novel high-risk devices, unless manufacturers provide sound justification for alternative approaches. However, for legacy devices (i.e., those with extensive historical use but limited pre-market data) Level 4 high-quality PMCF surveys bridge the evidence gap when complemented by existing data sources. Still, Notified Bodies will encourage or require additional PMCF activities, such as registries or targeted observational trials, when the device introduces new materials, indications, or risk factors that can impact patient outcomes clinically. High-quality surveys alone are accepted only if they demonstrate relevant safety and performance outcomes with sufficient depth in the context of the manufacturer’s documented knowledge of the device. Advantages of High-Quality PMCF Surveys When executed effectively, high-quality PMCF surveys offer multiple advantages: Efficient and scalable: enable manufacturers to gather data across diverse regions and clinical settings faster and at lower cost than clinical trials. Broader patient reach: sample large populations, revealing long-term or rare complications not captured pre-market. Cost-effective: especially for startups, provide meaningful evidence without the financial burden of a full post-market study. Regulatory acceptance of real-world data: regulators increasingly find value in real-world evidence (RWE). A high-quality PMCF survey complements clinical trials by filling data gaps such as device use in specific subgroups or patient-reported outcomes over time. For example, a novel cardiovascular implant with a prior pre-market study could use a high-quality PMCF survey to continually gather longitudinal safety and usability data from several countries, thereby strengthening its evidence base and supporting ongoing conformity under MDR. Limitations and When High-Quality PMCF Surveys May Not Suffice Despite their benefits, even high-quality PMCF surveys have inherent limitations. Even the best-designed surveys are observational and non-interventional, and therefore vulnerable to reporting and sampling bias. For new or high-risk implants, regulators often expect PMCF clinical studies that can capture hard endpoints including survival, revision rates, or verified adverse event frequencies in monitored settings. Key limitations of high-quality PMCF surveys include: Potential bias: respondent recall or sampling bias may distort findings. Sample size constraints: adequate statistical power is critical—detecting rare events may require large datasets. Data depth: surveys rarely provide comprehensive outcomes data or comparator arms typical of clinical studies. Under EU MDR, manufacturers justify why their chosen PMCF methods, whether surveys, registries, or trials, are adequate to maintain conformity. For novel or high-risk devices, Notified Bodies may determine that surveys alone do not provide sufficient clinical evidence, prompting requests for additional PMCF studies. Typical cases where surveys alone are insufficient include: Brand-new Class III implants without long-term safety data. Devices that use new technologies or materials with limited clinical history. Devices intended to sustain life, where the consequences of failure are severe. In these cases, regulators generally expect high-quality PMCF surveys to complement an existing evidence framework that includes registries and clinical trials. Recent Trends and Notified Body Feedback Since EU MDR enforcement, high-quality PMCF surveys have surged in popularity as a preferred tool for collecting real-world evidence. However, Notified Bodies scrutinize methodologies closely—only decision-grade high-quality PMCF surveys that demonstrate statistical and scientific rigor are accepted. RQM+ and other regulatory experts emphasize several success factors: Define objectives and endpoints clearly in the PMCF plan. Ensure traceability and transparency—document design, sampling, and analysis logic in detail. Follow MDCG guidance for PMCF planning and execution. Justify the evidence level for the device risk per EU MDR Article 61. Panel discussions hosted by RQM+ highlight that regulators value high-quality PMCF surveys when they are methodologically sound. Poorly designed surveys, such as those with vague endpoints, low response rates, or anecdotal feedback, may be rejected during conformity assessments. Closing Thoughts on High-Quality PMCF Surveys So, are high-quality PMCF surveys enough for high-risk devices? The answer is: yes, but only with strong justification in the context of existing evidence.  High-quality PMCF surveys, if designed with robust methods, provide meaningful real-world data and meet MDR evidence requirements for some high-risk or legacy devices. However, they are not sufficient on their own for novel, high-risk, or life-sustaining technologies. Manufacturers should integrate PMCF surveys as part of a comprehensive evidence strategy to complement post-market surveillance, registries, follow-up studies, or literature reviews. When surveys are used, ensure they are scientifically rigorous: clinically focused, designed for target users, and statistically powered. Ultimately, regulators welcome high-quality PMCF surveys that match the device’s risk classification, intended purpose, and can deliver the clinical insights necessary to demonstrate continued safety and performance. For some high-risk devices, a high-quality PMCF survey can indeed be enough.In case you missed it, watch the on-demand panel discussion "PMCF Surveys That Survive Scrutiny: What Reviewers Want and How to Deliver". #### Artificial Neural Network Supporting Biological Neural Networks Picture the sci-fi trope of a human brain, connected by wires, controlling a machine simply by conscious thought or even just passive physiology. Visions of the media-pervasive Neuralink1,2,3 may come to mind, but this device does not stand alone in its ability to tap into human neurons to control other physiological functions. Although we’re not talking The Singularity4 just yet, we are at a time when artificial neural networks and biological neural networks have become intertwined for the benevolent purpose of medical treatment. The latest developments in brain computer interface involve modeling human cognition. This is an exciting, sci-fi version of technology; however, there are much more practical examples of the artificial-to-biological bridge that help patients on a broader scale. Enabling closed-loop systems like these can allow patients with Parkinson’s disease, essential tremor, epilepsy, and other neurological conditions to thrive. Can it be Trusted? Theoretically, technology like adaptive DBS provides a safer and more effective delivery of electrical stimulation than its conventional counterpart. The concern lies in taking control out of the hands of a human and giving it over to a machine. Regulatory bodies are learning to keep up with innovation while ensuring patient safety as artificial intelligence (AI)-based devices seek market approval. Both the most recent AI-enabled device guidance in the US7 and the new AI Regulation in the EU8 introduce requirements related to training and testing any AI algorithms incorporated into medical devices. They call for documentation of the size and variability of training sets to reduce bias in the model, allowing it to be applicable to the entire intended patient population. They also outline requirements for testing that include both validation of the AI algorithm used as well as clinical testing to confirm safety and performance when used for its intended purpose. These robust assessments combined with continuous post-market assessments aim to prioritize safety while allowing for advanced technologies to reach patients with neurological disorders. How Does it Work? Neurological diseases, in particular, can benefit from this type of closed-loop system that receives input from the patient’s own physiological signals to determine the most appropriate output, for example electrical stimulation. This type of technology is gaining traction in the field of deep brain stimulation (DBS), dubbed “adaptive DBS.” Although DBS has long been an effective treatment for Parkinson’s disease, it has historically involved little variability in the current, frequency, and sequencing of electrical pulses to the brain other than “on” or “off”. Adaptive DBS, however, is dynamic and driven by the patient’s neurological function. If the neurological sensor detects waveforms associated with Parkinson’s tremor onset, the device can adapt to deliver the optimal amount of stimulation to ease the patient’s symptoms.5,6 Let's Make Neurology Happen Adaptive DBS offers one example of the advancements that AI technologies can bring to the field of neurological treatments. The automated nature of these systems relieves some of the burden from patients and caregivers and allows for a more customized treatment paradigm. This integration of artificial and biological neural networks offers promising advancements in medical treatment for neurological diseases on a practical level. As the frontier between artificial and biological intelligence continues to blur, the potential to transform neurological care becomes not just a possibility, but a reality. Adaptive deep brain stimulation and similar innovations are already reshaping how we treat complex conditions like Parkinson’s disease and epilepsy—offering patients more responsive, personalized, and effective therapies. If you're navigating the challenges of integrating or managing neurological devices, we're here to help. Contact us today to learn how we can support your journey with cutting-edge neurotechnology. Looking for more neurology device advice? Join us on the 26th of June for a live panel discussion, "Electric Brains & Regulatory Pains: Accelerate Neurology Innovation, Slash Risk, & Win Approval", where our experts will provide practical insights to help your organization successfully commercialize innovative neurological products. References Precise Robotically IMplanted Brain-Computer InterfacE (PRIME), NCT06429735. Neuralink Corp Control of Assistive Devices Via Brain-Computer Interface Technology (CONVOY), NCT06710626, Neuralink Corp Precise Robotically Implanted Brain-Computer Interface for the Control of External Devices (CAN-PRIME), NCT06700304, Neuralink Corp Kurzweil, Ray (2005). The Singularity is Near. New York: Viking Books. ISBN 978-0-670-03384-3. Krauss JK, Lipsman N, Aziz T, Boutet A, Brown P, Chang JW, Davidson B, Grill WM, Hariz MI, Horn A, Schulder M, Mammis A, Tass PA, Volkmann J, Lozano AM. Technology of deep brain stimulation: current status and future directions. Nat Rev Neurol. 2021 Feb;17(2):75-87. Beudel M, Brown P. Adaptive deep brain stimulation in Parkinson's disease. Parkinsonism Relat Disord. 2016 Jan;22 Suppl 1(Suppl 1):S123-6. Artificial Intelligence-Enabled Device Software Functions: Lifecycle Management and Marketing Submission Recommendations: Draft Guidance for Industry and Food and Drug Administration Staff, January 2025. Regulation (EU) 2024/1689 #### Beyond Inclusion: Reimagining Equity and Real-World Impact in Heart Failure Trials Introduction: A New Paradigm for Diversity in Heart Failure Trials As the FDA prepares to implement groundbreaking diversity guidance in 2025, clinical trials must account for demographic metrics such as age, sex, race, and ethnicity. While this focus marks a pivotal step toward healthcare equity, addressing traditional diversity alone is insufficient for conditions as complex as heart failure (HF). Conditions such as heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) disproportionately affects underrepresented populations, with Black and Hispanic communities experiencing 2-3x higher HF-related hospitalizations compared to White populations, yet remaining underrepresented in trials. Compounding this issue, HF research often overlooks disease heterogeneity and comorbidities central to patient outcomes. These include obesity, diabetes, chronic kidney disease (CKD), and pulmonary hypertension, factors that are frequently excluded to simplify trial design and regulatory pathways. Such exclusions, while streamlining regulatory approval, fail to reflect real-world patient populations and payer demands for real-world effectiveness and economic value. To truly transform HF care, trials must embrace a holistic framework that integrates demographic, socioeconomic, and clinical diversity.At RQM+, we recognize that inclusive trial designs serve both scientific rigor and strategic goals. By incorporating broader diversity into HF trials, manufacturers can achieve regulatory alignment, payer confidence, and expanded market access, while delivering transformative solutions for patients. The Case for Expanding Equity and Diversity in HF Trials Key Challenges in Current HF Trials Demographic Underrepresentation Intersectionality of Barriers: Women, Black, and Hispanic patients often face overlapping barriers such as limited access to trial sites, cultural mistrust of medical research, and socioeconomic constraints. Women: Despite representing the majority of HFpEF cases, women are underrepresented in HF trials, limiting insights into sex-specific therapeutic responses. Racial and Ethnic Minorities: Black and Hispanic populations face disproportionately high HF burdens but remain underrepresented, particularly in studies conducted in high-income countries. Exclusion of Complex Patients Missed Complexity: Patients with obesity, diabetes, CKD, or atrial fibrillation (AF) are often excluded due to procedural risks, despite representing large segments of the HF population. Magnified Inequities: Intersectionality compounds disparities, such as a Black woman with CKD and HFpEF, who is unlikely to be included in traditional trial designs. Geographic Imbalances Disparity in Trial Locations: Most HF trials are concentrated in high-income countries, leaving low- and middle-income countries (LMICs) underrepresented despite rising HF prevalence. LMIC inclusion provides globally applicable data, vital for payer adoption in diverse markets. Missed Subgroup Analyses Opportunities for Precision Medicine: Even when diverse populations are included, outcomes are rarely stratified by demographics or comorbidities, limiting insights into therapeutic effectiveness across subgroups Expanding the Definition of Diversity: Beyond Demographics Populations Typically Excluded in HF Trials Obesity-Associated HFpEF Rationale: Obesity drives unique metabolic and hemodynamic dysfunctions. Opportunity: Evaluating device therapies in this population can demonstrate real-world effectiveness, particularly in reducing hospitalizations and improving QoL. Obesity-specific endpoints, such as weight-adjusted functional capacity, could further strengthen the evidence base for payers (thus aligning better with payer interests) and improving real-world applicability. Diabetes Mellitus Rationale: Diabetes exacerbates HF but is often excluded due to complication risks. Opportunity: Combining device therapies with pharmacologic agents like SGLT2 inhibitors could show synergistic benefits and appeal to payers. This would address a significant unmet need, as diabetic HF patients represent a rapidly growing and high-cost subgroup. Chronic Kidney Disease (CKD) Rationale: CKD complicates HF management due to volume overload and reduced clearance. Opportunity: Trials including CKD patients can highlight cost-effectiveness in this high-cost group. Real-world studies of CKD patients could also demonstrate long-term savings by reducing dialysis dependence and hospitalizations. Combined Pre- and Post-Capillary Pulmonary Hypertension (CpcPH) Rationale: Advanced HF populations with pulmonary hypertension have few therapeutic options. Opportunity: Demonstrating effectiveness in reducing RV strain and improving hemodynamics could expand device indications. Frailty and Sarcopenia Rationale: Frail patients face unique challenges but represent a high-symptom burden subgroup. Opportunity: Trials targeting mobility and QoL outcomes can showcase device benefits beyond survival endpoints. Including this population would align trial designs with the goals of value-based care, where improving QoL is a key metric. Atrial Fibrillation (AF) Rationale: AF is a common HF comorbidity but often excluded due to rhythm-device interactions. Opportunity: Including AF patients can validate therapies that address rhythm and hemodynamic dysfunction simultaneously. Designing Inclusive Trials for Better Effectiveness and Reimbursement Broaden Eligibility Criteria Include comorbid populations such as those with obesity, CKD, and AF to better reflect real-world complexity. Incorporate adaptive trial designs to adjust cohort composition in real-time based on interim analyses. Bold Addition: Use stratified enrollment strategies to capture a broader spectrum of disease phenotypes. Leverage Wearables and Remote Monitoring Collect real-time data on patient activity and hemodynamics to capture QoL improvements, a key metric for payers. Bold Addition: Incorporate advanced wearables like implantable sensors for continuous monitoring of arrhythmias and exercise capacity. Expand Geographic Representation Conduct trials in LMICs to generate globally relevant data and address disparities. Build collaborations with local health systems and NGOs to overcome logistical barriers in LMICs. Bold Addition: Build cross-continental trial networks to balance equity and market alignment. Prioritize Subgroup Analyses and Long-Term Outcomes Stratify results by demographic and comorbidity variables to build a precision medicine narrative. Bold Addition: Extend follow-ups beyond 5-10 years to address durability concerns in heterogenous populations, for both regulatory and payer needs. Integrate Social Determinants of Health (SDOH) Include data on socioeconomic status to understand barriers to treatment adherence and outcomes. SDOH metrics, such as access to care or transportation, can help refine implementation strategies post-approval. Leverage AI models to analyze SDOH factors, offering actionable insights into improving trial accessibility and outcomes. Strategic Benefits for Medtech Manufacturers Regulatory Success: Inclusive trials align with FDA and EU Health Technology Assessment (HTA) expectations, minimizing approval delays. Reimbursement Confidence: Real-world evidence strengthens the case for payer support, particularly in high-cost populations. For example, trials that demonstrate cost savings in CKD or diabetic patients could secure favorable reimbursement terms. Global Market Adoption: Broader trial populations enhance global applicability, increasing clinician and patient adoption. Ethical Leadership: Addressing equity builds trust among underrepresented communities and stakeholders. Risk Mitigation: Comprehensive trial data reduces post-market risks, such as adverse events or product recalls, safeguarding long-term success. Conclusion: A Broader Vision for Heart Failure Trials As the FDA’s 2025 diversity guidance approaches, MedTech manufacturers must move beyond traditional diversity metrics to include the heterogeneity and comorbidities that define real-world HF populations. Innovative trial designs leveraging advanced technologies and global networks offer a pathway to transformative HF care. RQM+ excels at designing inclusive trials that meet regulatory standards, generate payer-aligned data, and deliver impactful patient outcomes. Together, we can redefine HF research, ensuring innovative therapies are accessible and equitable for all. Let’s lead the future of HF care with innovation, inclusion, and impact. Contact us here. Further reading - Bridging Treatment Gaps in Heart Failure with Reduced Ejection Fraction: Advancing Evidence for Device-Based Therapies #### Braving the Tariff Storm: Strategies for MedTech Companies The U.S. administration has announced plans to implement a 25% tariff on imported medical technologies (MedTech), pharmaceuticals, and automobiles, set to take effect today, April 2, 2025. This significant policy shift will undoubtedly impact the MedTech industry, requiring companies to adapt their strategies to mitigate the financial burden. Considering recent political instability, it's crucial to reassess and optimize your supply chain and manufacturing processes. At RQM+, we understand the complexities and challenges that come with such regulatory changes. With a collective 50 years of direct FDA experience and 20 years combined notified body experience, our team is here to provide regulatory guidance and strategic advisory to help you navigate this tariff storm effectively. Protect Your Margins In response to the increased tariffs, RQM+ offers optimized regulatory and supply chain strategies to protect your margins. Here are three potential actions you might consider: Bring Manufacturing into the U.S. Transfer Process: Moving manufacturing from overseas locations to the U.S. can be a significant process unless a duplicate process is already in place at a U.S. facility. If a qualified line exists in the U.S. and we are looking to expand the line, there may be an opportunity to move faster, but savings might be limited or the increased costs even higher than the tariffs. New Manufacturing Capability: Setting up a new manufacturing capability with full setup and qualification of a new line is a longer-term strategy and may take 1-2 years. In addition to the infrastructure costs, the increased production cost may offset any benefit of avoiding the tariff in the short-term, which would require additional due diligence to justify the cost of the move. Optimize Supply Chain for Non-U.S. Distribution Final Packaging and Release: If products are manufactured in a low-cost country (LCC) and shipped to a U.S. site for final packaging and release, it may be practical to set up the site for product release and ship directly to non-U.S. distribution points without entering the U.S. and being subject to potential tariffs. Certification Process: If the site is set up as a manufacturer, qualifying a release process may be accomplished in 3-6 months. If the non-U.S. manufacturing site is not registered and certified as a medical device manufacturer, the certification process can be extensive and costly (6-18 months), factors that need to be evaluated if considering a longer-term strategy. Local Supplier Selection and Qualification Local Production Benefits: Selecting and qualifying local suppliers to manufacture parts for assembly in a U.S. production facility may bring additional benefits, such as tighter control of the supplier and shorter, more stable supply chains. A local supply chain may reduce the time needed to implement future changes to a few months, compared to those typical with LCC supply chains of 6-12 months, allowing for reduced scrap costs and improved supplier controls throughout the change process. Rapid Implementation: For smaller companies with limited in-house manufacturing capacity, moving from a supplier in China or another LCC to one nearby may bring advantages that allow for faster responsiveness to customer needs that offset some of the cost considerations Leveraging RQM+ FDA Experience Given the uncertainty, MedTech companies need trusted partners with deep regulatory expertise to help them navigate evolving approval processes. RQM+ has former FDA experts who have worked inside the agency and understand how regulatory decisions are made. Our team of ex-FDA professionals helps anticipate potential roadblocks and ensures regulatory strategies are aligned with evolving expectations. Looking for additional insights from RQM+ subject matter experts? Check out a recent LinkedIn article by VP, Global Regulatory Affairs, Dr. Jaishankar Kutty, MedTech Tariffs: A Strategic Guide for an Industry Under Siege. Contact Us Need help navigating these new tariffs? Contact us today. Our friendly team at RQM+ is ready to assist you in addressing market uncertainty and ensuring your MedTech products remain competitive. We're here to make your MedTech happen! #### Breaking New Ground: Introducing the Transitional Coverage for Emerging Technologies (TCET) Pathway This blog post explores the CMS and AHRQ's proposed TCET pathway, which aims to improve beneficiary access, reduce coverage uncertainty, encourage evidence development and coordinate benefit categories for emerging technologies. It also discusses eligibility criteria for breakthrough devices and the self-nomination process for manufacturers. Transitional Coverage for Emerging Technologies On 22 June 2023, the Centers for Medicare and Medicaid Services (CMS) issued a notice with comment period regarding the process CMS proposes to use for providing Transitional Coverage for Emerging Technologies (TCET) through the National Coverage Determination (NCD).  CMS will accept comments from the public on the proposed TCET pathway for 60 days after the date of publication. The newly proposed TCET pathway, developed in partnership with the Agency for Healthcare Research and Quality (AHRQ), is intended to balance multiple considerations when making coverage determinations.  These include: Facilitating early, predictable and safe beneficiary access to new technologies Reducing uncertainty about coverage by evaluating the potential benefits and harms of technologies with innovators early on Encouraging evidence development if notable evidence gaps exist for coverage purposes In addition, the TCET pathway will allow any evidence gaps to be addressed through fit-for-purpose studies. Fit-for-purpose studies are those where the study design, analysis plan, and study data can appropriately answer the research question(s).  The TCET pathway will also assist in coordination of benefit category determination, coding and payment reviews. Breakthrough Devices CMS is coordinating with the Food and Drug Administration (FDA) and manufacturers of Breakthrough Devices to ensure timely Medicare coverage decisions following the FDA market authorization. Not all devices are eligible for the TCET pathway.   Candidates for the TCET pathway includes devices that are:  Certain FDA-designated Breakthrough Devices  Fall within a Medicare benefit category Not already coverage of an existing Medicare NCD Not excluded from coverage through law or regulation   For the TCET pathway, CMS is using the current NCD and Coverage with Evidence Development (CED) processes. Coordination with the AHRQ will continue. Evidence development to support Medicare coverage is a key component of the TCET pathway. TCET Nomination Manufacturers can self-nominate for voluntary participation in the TCET pathway. CMS will review the nomination, which includes an initial meeting with the manufacturer, discussions with FDA and a benefit category determination. CMS will notify the manufacturer if it accepts the manufacturer’s nomination for the TCET pathway.  In those cases where CMS does not accept a nomination, CMS will meet with the manufacturer and discuss other coverage pathways.   CMS and manufacturers have the option to withdraw from TCET anytime up until CMS opens the NCD by posting the tracking sheet. How RQM+ Can Help At RQM+, we know that the path to reimbursement is not linear, and we have the experience to guide clients to the best solution from day one. We have expertise across a broad range of devices and throughout the entire reimbursement product lifecycle. Our reimbursement services range from initial reimbursement strategy development to post-approval market access support. If you'd like to begin a conversation about how we can help, please complete our contact form below. Begin Your Reimbursement Journey #### Bridging CDER, CBER, and CDRH: Surviving the Regulatory Bermuda Triangle of Combination Products By Gee Burke MD PhD, recently former FDA (CDER) Ask any manufacturer of combination products, and they’ll tell you the same thing: one wrong move with the FDA’s three-headed monster: CDER, CBER, and CDRH, and your program can vanish into regulatory purgatory. I know, because I used to sit on the inside of that labyrinth at FDA. Combination products promise enormous clinical impact. But if you don’t know how to navigate the Bermuda Triangle formed by CDER, CBER, and CDRH, you may be sailing blind while you incorrectly assume you are charting a path to approval. Who Really Runs the Show? Understanding the Centers The FDA regulates combination products through three key centers: CDER (Center for Drug Evaluation and Research) for drug-led products. CBER (Center for Biologics Evaluation and Research) for biologic-led products. CDRH (Center for Devices and Radiological Health) for device-led products. The lead depends on the product's Primary Mode of Action (PMOA), the component of the product that provides the principal therapeutic effect. If the PMOA is unclear, the FDA Office of Combination Products (OCP) can assign the responsible center via a Request for Designation (RFD) process. Figure 1: Example flowchart depicting the overview of FDA regulatory pathways1 Insider reality checkIn practice, this “assignment” isn’t always as neat as the flowcharts make it look. Centers often jockey behind the scenes, and if you haven’t prepared your justification carefully, expect delays, or worse, conflicting asks from multiple reviewers. Real-World Examples (and What They Teach Us) Drug-Eluting Stents: Typically reviewed by CDRH, but CDER’s input on drug kinetics is critical. I’ve seen too many teams stumble here by underestimating how early CDER wants to see stability data. Don’t make that mistake. Prefilled Syringes:. Syringes with vaccines, insulin, or biologics sit under CDER or CBER, with CDRH chiming in. What people forget: human factors data can sink you if you treat the syringe like “just a container.” Transdermal Patches: This device/drug combination delivers medication through the skin. CDER commonly leads with advice from CDRH. The trap? Oversimplifying device manufacturing controls. FDA won’t. Encapsulated Cellular Therapies:. CBER usually leads, but device performance is central. Here, reviewers ask questions most teams never anticipate, like device biocompatibility over long-term implantation. The Regulatory Bermuda Triangle in Action Jurisdictional Complexity Combination products demand careful center assignment, as the lead center sets the regulatory requirements (GMP, QSR, IND, NDA, BLA, 510(k), PMA, etc.) and post-market obligations. Ambiguous PMOAs can generate jurisdictional disputes, risking costly review delays. Intercenter Collaboration The reviewing center often lacks deep expertise in all product aspects. Intercenter agreements allow consultation (e.g., CBER might lead but must seek CDRH advice for a device component). Proactive, early communication with FDA and clear documentation about product attributes help streamline assignments and avoid confusion. Inside FDA, I watched files stall simply because one center hadn’t responded to another’s consult request. Regulatory Pathway Cheat Sheet Product Example Components Lead Center Designation Submission Type Drug-eluting stent Device & Drug CDRH or CDER PMA & NDA combo Prefilled syringe Device & Drug/Biologic CDER or CBER NDA/BLA & device data Transdermal patch Device & Drug CDER NDA, with device data Cell therapy w/ device Device & Biologic CBER BLA & device section Pro tipDon’t treat this table as gospel. FDA may flex based on evolving science, safety signals, or political pressures. Always verify assumptions early. Surviving the Triangle: Practical Tips Map your product’s modes of action early and prepare justification for PMOA. Engage FDA through Pre-RFDs or formal RFDs at the earliest opportunity. Build integrated development plans that cover drug, device, and biologic regulations (e.g., 21 CFR 210/211 and 820, as needed). Expect and plan for cross-center consultation. No single center holds all the expertise your product may require for approval. Maintain regulatory updates in FDA policies or OCP guidance. Emerging watchpoints: Digital drug-delivery platforms, AI-enabled injectors, and gene/cell therapies with embedded delivery devices are rewriting the rules as we speak. If your regulatory strategy looks backward instead of forward, you’re already behind. Final Word Combination products open new therapeutic frontiers, but their regulatory path requires focus to avoid getting lost in the Bermuda Triangle. Mastering center assignments, regulatory pathways, and necessary cross-functional collaboration is the route to both regulatory survival and commercial success. Combination products don’t have to disappear into the regulatory abyss. With the right strategy, you can chart a safe course. Having lived inside the FDA’s Bermuda Triangle, team RQM+ with expert strategic and tactical guidance from me help manufacturers be a regulatory and commercial success.  If your program sits at the intersection of CDER, CBER, and CDRH, don’t leave your future to chance. This is where my experience inside the FDA becomes your greatest competitive edge. Exploring MedTech Consulting? Full-service support isn’t just about doing more, it’s about designing stronger, more resilient product strategies from day one. Whether you’re bringing a first device to U.S. market or responding to shifting regulations, a partner like RQM+ brings the agility, depth, and cross-functional horsepower to accelerate progress with confidence. For MedTech leaders, the upside is clear: fewer delays, lower risk, and a faster path to clinical impact. Prefer to start quickly? Begin with a consultative conversation. For more reading - Laboratory Developed Tests: Current State of Play FAQ Naderi-Meshkin, H et al. (2018). Critical Issues in Successful Production of Skin Substitutes for Wound Healing. Journal of Genes and Cells. 4. 10. 10.15562/gnc.63. #### Bridging the Real-World Evidence Gap in MedTech - A practitioner’s guide to applying real-world data in regulatory strategy. Why Real-World Evidence Matters Regulators are increasingly open to real-world evidence (RWE) as a foundation for market entry, indication expansion, and post-market surveillance. Both the FDA and EU regulators recognize that randomized controlled trials can be overly burdensome and alone cannot capture the realities of device use in everyday clinical practice. Real-world evidence offers manufacturers a path to demonstrate ongoing safety, performance, and value without defaulting to costly or impractical studies. The opportunity is clear, but leveraging real world evidence effectively requires a strong grasp of the data sources, their strengths, and their limitations. Defining the Basics: RWD vs. RWE Real-world data (RWD) is information on patient health or healthcare delivery that is routinely collected in clinical practice. This includes data from medical records, claims, registries, surveys, and digitally connected devices. Real-world evidence (RWE) is what happens when this data is systematically analyzed to evaluate safety, performance, and other outcomes of interest. The distinction is subtle yet important. Data alone is not sufficient—its transformation into evidence is what regulators use to support decisions. Where RWE Fits in Regulatory Strategy RWE is most commonly applied to confirm safety and performance in the post-market phase as it is being used in standard care. Its potential, however, extends much further. It can support the expansion of indications when physicians pioneer new uses in practice, provided manufacturers are prepared to capture and analyze that data. It can also be applied to initial submissions in new regions, as long as differences in demographics, clinical practice, and standards of care are recognized and justified. In addition, RWE drawn from equivalent or similar devices can be used to benchmark performance or strengthen the design of a clinical investigation. The value is clear: RWE creates regulatory flexibility when applied strategically. Methods Use of RWE is not new to regulatory submissions. Historically, this evidence has been captured by retrospective chart reviews, registries, and claims data. Traditional retrospective chart reviews generate patient-level data but are limited to what is recorded during routine care, registries provide long-standing, regulator-accepted evidence but often lack device-specific linkage or complete follow-up and claims data, offers large structured datasets but rarely captures outcomes. More innovative approaches, such as survey-based chart reviews, allow healthcare providers to supply patient-level insights alongside reports of their own experience with the device. Comprehensive electronic health record datasets allow sponsors to see longitudinal outcomes across integrated systems, though linkage and access to unstructured notes remain challenges. Finally, the growing presence of wearables and connected devices allow for the creation of continuous streams of information, including patient-reported outcomes, that manufacturers can leverage with the proper consent. Regulatory Considerations It is important to recognize that RWE is not exempt from the rigor expected of clinical studies. Ethics approvals, formal protocols, and appropriate risk assessments are still required. The difference lies in the risk profile. Because RWE is observational and does not interfere with patient care, the main risk is disclosure of sensitive patient information.Regulators also expect statistically sound sample sizes. The justification should be based on a defined objective and acceptance criterion for the primary endpoint. Submissions must be backed by robust design and statistical rationale to avoid rejection or deficiency findings. Emerging Frameworks: The EU Health Data Space The European Health Data Space has the potential to greatly expand the accessibility of RWD. While its primary aim is to ensure continuity of care across the EU, it also designates industry as a beneficiary of secondary uses, including research and innovation. The practical details are still evolving, but the regulation signals a future where access to de-identified health data across borders may become more streamlined. For manufacturers, this could open new opportunities to build evidence more efficiently and across broader patient populations. Practical Takeaways for Regulatory Teams The key is to determine the need for generating clinical evidence, and to choose a method that is fit for purpose. There is no universal approach, and strategies must align with the device, the regulatory pathway, and the availability of data. Teams that embrace innovative methods like survey-based chart reviews or EHR datasets will be able to close evidence gaps faster and more efficiently than those relying solely on traditional investigational approaches. Justification remains central: whether bridging geographies, expanding indications, or using alternative comparators, regulators expect a clear and defensible rationale.Engaging early with regulators is critical. Pre-submissions in the US or structured dialogues in the EU can clarify expectations and prevent missteps. Finally, teams should anticipate evolving access models. Frameworks like the EU Health Data Space will continue to reshape what is possible and what regulators are prepared to accept. Key Take-AwayReal-world evidence is not a shortcut. It is a powerful complement to traditional studies when applied with precision. For MedTech teams, mastering the nuances of RWE collection and analysis can reduce costs, accelerate timelines, and strengthen submissions. Most importantly, it ensures that the regulatory strategy reflects the true performance of devices where it matters most: in the real world. Exploring Outsourcing Clinical Trials in MedTech? Full-service support isn’t just about doing more, it’s about designing stronger, more resilient product strategies from day one. Whether you’re bringing a first device to U.S. market or responding to shifting regulations, a partner like RQM+ brings the agility, depth, and cross-functional horsepower to accelerate progress with confidence. For MedTech leaders, the upside is clear: fewer delays, lower risk, and a faster path to clinical impact. Prefer to start quickly? Begin with a consultative conversation. #### Bridging Treatment Gaps in Heart Failure with Reduced Ejection Fraction: Advancing Evidence for Device-Based Therapies Heart failure with reduced ejection fraction (HFrEF) is a progressive condition affecting millions worldwide, imposing both a clinical and economic burden on patients and healthcare systems. While guideline-directed medical therapy (GDMT) remains the cornerstone of treatment, its underutilization, exacerbated by clinical inertia and the challenges of managing comorbidities, continues to limit patient outcomes  As the disease advances, a critical gap emerges between the stabilizing effects of GDMT in the early stages and the necessity for advanced interventions like left ventricular assist devices (LVADs) or heart transplantation in pump failure. Emerging device-based therapies are now reshaping the treatment landscape, offering new solutions for structural and functional remodeling of the left ventricle (LV) and addressing unmet needs in intermediate stages of heart failure.  To support the adoption of these therapies, clinical trials must do more than validate safety and effectiveness, they must also demonstrate reductions in mortality, hospitalizations, and disease progression to justify reimbursement. RQM+, as a leading CRO in the MedTech space, is uniquely equipped to design and execute trials that bridge these gaps. By integrating economic analyses and real-world evidence, we can help MedTech innovators align device-based therapies with payer requirements, advancing their adoption and ensuring access for patients who need them most.  Through collaboration with MedTech innovators, RQM+ is committed to transforming the HFrEF landscape, combining pharmacologic and structural interventions to deliver improved outcomes for patients, providers, and payers alike.   Introduction  Managing HFrEF requires a structured, multi-phase approach, starting with GDMT. This cornerstone therapy including beta-blockers, ARNIs, MRAs, and SGLT2 inhibitors, has been proven to reduce morbidity, mortality, and hospitalizations. However, its underutilization, driven by clinical inertia, the underappreciation of risk, and the complexity of patient comorbidities, deprives many patients of its benefits. The progression of heart failure typically follows distinct phases: an onset stage, where GDMT is most effective; a relatively stable phase, during which disease management focuses on maintaining stability; a period of episodic decompensation, where the heart progressively struggles to maintain function; and, eventually, pump failure, when advanced, expensive interventions such as left ventricular assist devices (LVADs), or heart transplantation are required. GDMT plays a critical role in the onset stage, stabilizing patients and delaying progression. However, as the disease advances, GDMT alone often becomes insufficient. A significant gap in care exists in the transition from onset to eventual episodic decompensation. While cardiac resynchronization therapy (CRT) can help select patients, eligibility is limited, leaving a large subset of patients without viable treatment options. This gap is further compounded by clinical inertia resulting in the underutilization or delayed escalation of GDMT. Contributing factors include hesitancy to manage side effects, insufficient familiarity with therapy titration, and an underappreciation of the risks of inaction during the early stages of the disease. These challenges lead to more frequent hospitalizations, a decline in quality of life (QoL), and accelerated disease progression. Once pump failure sets in, treatment options narrow significantly. LVADs and heart transplantation are invasive, resource-intensive, and reserved for a small fraction of patients due to stringent criteria, high costs, and limited availability. To address these gaps, greater adherence to GDMT from the onset is essential, but this alone is insufficient. The development and integration of innovative device-based therapies are critical to bridging the intermediate stages of care between disease onset and pump failure. Emerging devices such as mitral valve repair systems, intramyocardial reshaping tools, and others provide new opportunities to enhance outcomes for patients whose heart function deteriorates despite optimal GDMT. The following sections will explore the reimbursement landscape for these device-based therapies, highlighting the importance of achieving hard clinical endpoints to justify payer support. Additionally, we will examine novel devices poised to address the intermediate gap in HFrEF care, focusing on their real-world effectiveness and measurable patient outcomes. RQM+ is committed to designing and executing trials that evaluate these therapies, demonstrating their ability to improve QoL, reduce hospitalizations, and slow disease progression, supporting broader reimbursement and access to effective treatments across all stages of heart failure. Expanding Focus: Reimbursement Considerations for HFrEF Device-Based Therapies Device-based therapies hold promise for addressing structural issues in heart failure management. However, achieving reimbursement requires a rigorous focus on hard clinical endpoints, beyond cost-effectiveness and QoL improvements. While the economic benefits of reduced hospitalization rates and improved QoL are compelling, payers require substantial evidence of clinical impact. Key hard endpoints to target include: Reductions in mortality: Showing a direct link between device use and decreased mortality rates among HFrEF patients can provide strong justification for payer support. Reduced hospitalizations: Demonstrating a clear reduction in heart failure-related hospitalizations and emergency interventions will further underline the value of these devices in stabilizing high-risk patients. Measurable improvements in heart function: Endpoints like reductions in LV volumes, improvements in LV ejection fraction, and enhanced six-minute walk test (6-MWT) results are critical in proving that device-based interventions deliver tangible physiological benefits. Enhancement Strategy for Reimbursement Support Integrate Hard Endpoints with Economic Analyses: To make a compelling case for reimbursement, future clinical trials should document both hard clinical outcomes and economic impacts, such as fewer hospitalizations and reduced long-term care needs. While cost savings alone may not suffice, pairing them with demonstrated health improvements can make a more persuasive argument. Prioritize Real-World Effectiveness: Given the variability in clinical trial settings versus real-world conditions, observational studies that document device effectiveness across diverse patient demographics are vital. By showing that hard endpoints are met consistently outside controlled environments, real-world evidence strengthens the case for payer coverage. Clinical and Device-Based Innovations in HFrEF: Addressing Gaps with Evidence-Driven Reimbursement Support Emerging device therapies including partitioning devices, reshaping tools, and mechanical support systems are poised to bridge intermediate gaps in care, demonstrating measurable improvements in patient outcomes and QoL. While these benefits are promising, achieving consistent reimbursement requires hard clinical endpoints (not only surrogate endpoints) that demonstrate substantial impact on patient outcomes. The following is a brief analysis of each device, along with proposed trials to validate their clinical and economic value. V-Sling System: Targeting LV dilation and wall stress, the V-Sling aims to restore normal LV shape and prevent further remodeling, complementing GDMT in cases of refractory heart failure. Pros: Demonstrated efficacy in reducing LV volume with a relatively straightforward implantation procedure. Cons: Potential issues with mechanical anchoring and long-term durability. Trial Suggestion: A study integrating hard clinical endpoints, such as reductions in hospitalization rates and mortality, alongside economic data could highlight the V-Sling’s role in stabilizing high-risk patients and reinforce its value to payers. MIRTH (Myocardial Intramural Remodeling by Transvenous TeTHer): Designed to reshape the LV from within, MIRTH is a structural solution for dilated cardiomyopathy that avoids impact on the right ventricle. Pros: Offers targeted reshaping with minimal procedural invasiveness, addressing the structural progression of HFrEF. Cons: Limited human data; primarily supported by animal studies and early clinical trials. Trial Suggestion: A trial comparing MIRTH plus GDMT to GDMT alone could establish its effectiveness in achieving endpoints like reductions in LV volumes and mortality, which are essential for payer support. Carillon Mitral Contour System: A percutaneous device for mitral valve repair, Carillon has shown improvement in LV function and reduced functional mitral regurgitation, enhancing both exercise capacity and quality of life. Pros: Minimally invasive with low procedural risk. Cons: Limited applicability for patients without FMR. Trial Suggestion: A payer-focused study assessing Carillon’s impact on six-minute walk test (6MWT) results, LV volumes, and hospitalization rates could help establish its value by focusing on hard endpoints and real-world effectiveness. ContraBand Pulmonary Artery Banding: This device regulates LV filling pressures via pulmonary artery banding, supporting patients with chronic HFrEF and DCM. Pros: Demonstrated improvements in exercise tolerance and hemodynamics. Cons: Limited suitability for patients with significant pulmonary hypertension. Trial Suggestion: A study demonstrating ContraBand’s effects on hard endpoints, such as reductions in hospitalizations and functional improvements, would provide valuable data for clinical adoption and reimbursement support. AccuCinch Ventricular Restoration System: Utilizing an anchor-and-tether system, AccuCinch reduces LV dilation and wall stress. Early data indicate improvements in LV ejection fraction and hospitalization rates. Pros: Durable LV volume reduction with a low adverse event rate. Cons: Requires large-bore access and advanced procedural expertise. Trial Suggestion: A multicenter study measuring hospitalization reduction, LV function improvements, and economic benefits could strengthen the case for reimbursement by showcasing both clinical and economic impacts. Proposed Clinical Trial Initiatives for HFrEF Integrated Multi-Device and GDMT Synergy Trials: Given the unique potential of device therapies to complement GDMT, multi-arm trials can help identify the most effective layered treatment strategies. A trial comparing GDMT alone, GDMT with the Carillon Mitral Contour System, and GDMT with AccuCinch would assess how combined therapies influence outcomes such as LV volume reduction, ejection fraction improvements, and overall mortality. Emphasizing hard clinical endpoints in these trials could demonstrate each combination’s value and establish best practices for layering pharmacologic and structural interventions. Real-World Effectiveness and Reimbursement Support Trials: By focusing on real-world effectiveness and economic outcomes, such as reductions in hospitalizations, emergency interventions, and healthcare utilization, these trials can generate critical data for payers. Incorporating metrics like quality-adjusted life years (QALYs) gained, reductions in readmissions, and long-term cost savings will make a strong case for reimbursement. Real-world data documenting consistent achievement of hard clinical endpoints across diverse demographics will underscore these therapies’ reliability outside controlled settings, bolstering support from both payers and clinicians. Longitudinal Outcomes and Durability Studies: Tracking patients over a 3-5 year period post-implantation with comprehensive GDMT can provide valuable insights into the long-term durability and effectiveness of these device-based therapies. By assessing hard endpoints such as sustained improvements in LV function, reduction in mortality, and fewer rehospitalizations, these longitudinal studies will build the evidence base needed to establish these devices as standard care, reinforcing their value proposition to both clinicians and payers. Patient-Centered Outcome Trials: Highlighting patient-reported outcomes (PROs) is essential to align clinical goals with patient needs and payer priorities. Trials focusing on meaningful, patient-centered metrics—such as improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, New York Heart Association (NYHA) classifications, and functional capacity (e.g., 6-MWT), can demonstrate tangible quality-of-life benefits. These outcomes resonate strongly with payers, providing a comprehensive view of device impact that includes both clinical and patient benefit-centric gains, facilitating broader adoption and coverage. Comparative Economic and Clinical Benefit Analyses: Given the significant cost disparity between pharmacologic and device-based therapies, it is essential to demonstrate not only clinical improvements but also how these benefits translate into economic value. A trial comparing hard clinical endpoints and associated healthcare costs among patients receiving GDMT alone versus those receiving layered device therapies could highlight cost offsets through reduced hospitalizations and emergency care. Demonstrating that devices can offer durable clinical benefits with justifiable economic impact is crucial for securing reimbursement. Conclusion The combination of GDMT and innovative device-based therapies holds transformative potential for redefining care in HFrEF. By addressing critical gaps in treatment, these therapies offer an opportunity to significantly improve patient outcomes while meeting the demands of modern healthcare systems. RQM+ is uniquely positioned to partner with MedTech innovators in designing and executing trials that go beyond validation, focusing on hard clinical endpoints, real-world effectiveness, and economic analyses that resonate with payers. Through our patient-centered, evidence-driven approach, we aim to establish these therapies as valuable and reimbursable options in the HFrEF landscape, ensuring broader access to life-changing interventions. With expertise spanning clinical innovation, regulatory strategy, and economic viability, RQM+ provides the strategic and technical capabilities to accelerate the journey from innovation to implementation. Together with our MedTech partners, we can shape a new paradigm in HFrEF care, one that seamlessly integrates pharmacologic and structural solutions to deliver exceptional outcomes and transform the lives of patients around the world. #### Brought to You by the Letter M: Operational Considerations for Transitioning From the QSR to the QMSR We used the publication of the final rule amending the US Quality System Regulations (QSR) as an example in our recent blog titled Enhancing Competitiveness in MedTech: Smart Strategies with Regulatory Intelligence. Here we will look at the final rule, and its implications in a little more detail. The FDA has now issued the final rule for the Quality Management System Regulation (QMSR) that amends the existing Quality System Regulations (QSR, 21 CFR 820). This amendment incorporates the requirements of ISO 13485:2016 by reference into the US regulations. ISO 13485:2016 has been incorporated by reference on the basis that ISO 13485:2016 is considered ‘substantially similar’ to the existing QSR. The requirements for the QMSR will therefore be ISO 13485:2016 requirements plus a few additional, US-specific, requirements that are laid out in the QMSR. The rule will be effective, and the FDA will begin to enforce the QMSR requirements, from 2nd February 2026. Until then device manufacturers are required to comply with the QSR. This gives device manufacturers two years to prepare and implement before the QMSR is enforced during FDA establishment inspections. Whirlwind tour: What has changed? The title of the regulation has changed from Quality System Regulation (QSR) to the Quality Management System Regulation (QMSR). The scope of the QMSR is unchanged from the QSR (i.e. QMS requirements do not apply to previously exempt products, and no new exemptions). The written content of the regulation has been reduced significantly, as shown by the reduction of the contents table in Figure 1, but the changes to specific requirements are mostly not significant as this is the basis for the FDA’s decision to incorporate by reference. Figure 1. Change in contents from QSR to QMSR As ISO 13485:2016 references ISO 9000:2015 as a normative reference for terms and definitions used within ISO 13485:2016, then the FDA has also incorporated by reference ISO 9000:2015. There are five terms that are not used, or not defined, in ISO 13485:2016 or in clause 3 of ISO 9000:2015 that are defined in the QMSR (21 CFR 820.3). All the terms and definitions given in section 201 of the Federal Food, Drug, and Cosmetic Act apply, and they supersede the correlating terms and definitions in ISO 13485:2016. Additionally, there are five terms that are defined in the QMSR, where those definitions supersede the correlating terms and definitions in ISO 13485:2016 or ISO 9000:2015; these are: Implantable medical device, Manufacturer, Organization, Rework, Safety and Performance. The phrase ‘applicable regulatory requirements’ is littered throughout ISO 13485:2016, but what does it mean for the QMSR if ISO 13485:2016 is incorporated in full? The FDA has provided some examples of where there are other US-specific regulatory requirements, outside of 21 CFR part 820, that come into play within the quality management system (§820.10 (b)). One example given is for clause 8.2.3 of ISO 13485:2016, reporting to regulatory authorities, where the manufacturer must notify FDA of complaints that meet the reporting criteria of 21 CFR part 803 in addition to the requirements of ISO 13485:2016 §8.2.3. Design controls are dead (well, will be soon), long live ‘design and development’. Ok please forgive me for the attention grabbing opening; only the term ‘design controls’ is going, not the concept and established principles. The incorporation by reference of ISO 13485:2016 means that design controls will now called by the ISO 13485 term, ‘design and development’. For the US, the applicability of these requirements to certain device classifications remains the same as it did under the QSR (§820.10 (c)). The QMSR maintains the requirement from the QSR that the ‘extra’ level of traceability for implantable devices from ISO 13485:2016 clause 7.5.9.2 also applies to ‘devices that support or sustain life’ (§820.10 (d)). The FDA considers there to be a need for additional requirements on top of those from ISO 13485:2016 regarding the control of records. Manufacturers must meet the requirements of ISO 13485:2016 clause 4.2.5 (and other applicable clauses) and the requirements of §820.35 of the QMSR. This includes specific requirements for records including complaint records and servicing records (§820.35). ISO 13485:2016 clause 7.5.1 requires production controls to include “implementation of defined operations for labelling and packaging”. The FDA does not think that ISO 13485:2016 sufficiently addresses the inspection of labelling by a device manufacturer, and thus more specific requirements are included in the QMSR (§820.45). By incorporating ISO 13485:2016 by reference, there is a perceived shift in the FDA’s approach to risk management. In the responses to the comments on the proposed rule, the FDA disagreed with this in their response to the comments received. Whilst there is no shift in philosophy, the clear requirements for integrating risk management principles throughout the total product life cycle is an advancement on the unspecified expectations documented in the QSR of 1996 (e.g. the requirement for risk analysis as part of Design Validation under §820.30 (g)). The incorporation of ISO 13485:2016 establishes a more explicit requirement for risk management throughout the quality management system, especially in design and development and post market surveillance (feedback) and enables a reference point for sound (and risk-based) decision making. As well as 21 CFR 820, the final rule also amends 21 CFR Part 4, which is the regulation of combination products. Subpart A (current Good Manufacturing Practice, cGMP, requirements for combination products) has been amended to reflect the changes made to 21 CFR 820 (i.e. reference to QMSR rather than QSR and inclusion by adoption of ISO 13485:2016 and ISO 9000:2015). Under §820.180 (General requirements) there was a requirement for records (required by the QSR) to be maintained, reasonably accessible and readily available for review and copying by FDA employees. There were some exemptions to this requirement, whereby §820.180 (c) permitted reports from Management review, internal quality audits and supplier audits did not have to be presented during FDA inspections. The QMSR removes this exemption. Fans of acronyms/initialisms (whichever you prefer to call them) will be disappointed to hear that the following terms have been dropped: Design History File (DHF), Device Master Record (DMR) and Device History Record (DHR). The requirement to document and maintain the records that made-up these three items has not been removed, as it is covered by the requirements of ISO 13485:2016, including clauses 4.2.3, 4.2.5, 7.3 and 7.5. What does this mean? It depends! Ok, back up. Why is this important? Well the US is the largest market for medical devices and IVDs 1, and survey data over the last few years points towards a shift away from Europe (EU and the UK) to the US and Canada as the first entry point for new medical devices 2-4. The continued issues with implementation of the MDR and IVDR in the EU, and the uncertainty of the UK regulatory landscape in the near-term is not going to turn that trend around in a short space of time. The effort involved in transitioning to new requirements is all proportionate to the gap between the old and the new. The size of that gap, and the impact of these changes depend on the following: the status of your quality management system (i.e. does it already conform to ISO 13485:2016 or not), your location, and your (current/prospective) sales markets.  At one end of the scale, an organisation whose quality management system currently complies with 21 CFR 820 but does not conform to ISO 13485:2016 will likely have the biggest challenge. The FDA believes that that the QSR and ISO 13485:2016 are substantially similar, which is true (in my opinion), but that does not guarantee that all of the requirements of ISO 13485:2016 are currently being met by the current quality management system. Somewhere in the middle, are those organisations that do not currently sell into the US but plan to in the future. These organisations likely have ISO 13485:2016 certification to support market access elsewhere but will now have to identify and close those gaps with the QMSR, particularly all of those related to the applicable US regulatory requirements (e.g. UDI, registration, medical device reporting, recalls). At the other end of the scale, if an organisation already has conformity to ISO 13485:2016 and compliance with 21 CFR 820 (QSR) then there is very little difference at a practical level. Sure, remediation work will be required but it will likely focus on documentation updates (e.g. for references or nomenclature) rather than new or updated quality system processes. The QMSR does not apply to suppliers, e.g. suppliers of raw materials, components, sterilisation services. The FDA, however, has suggested that it would good practice for suppliers to apply the requirements of the QMSR. Also, as part of supplier management and control over outsourcing, a manufacturer is likely to encourage their suppliers to work to similar quality system requirements. This trickle-down effect may see a wider adoption of the QMSR than just those to whom it is directly applicable. Now for some practical advice on what to do next… QMS Remediation The journey to update your quality management system to align with the new regulations may seem like another burden forced onto a quality team who are still recovering from implementing QMS changes for EU MDR and/or IVDR. In this instance, the gap is not so vast because the requirements of the QSR and ISO 13485:2016 are ‘substantially similar’. Regardless, all quality management system transitions begin with a gap assessment! A gap assessment is not strictly the same as an audit, because it is not based on sampling, it needs to look at all requirements to determine if they are met or not. The assessment should be performed by those who have made themselves familiar with the requirements of the QMSR and are knowledge in the interpretation and implementation of ISO 13485:2016 requirements. It is beneficial to use a well-structured assessment template, especially if the assessment is being performed by more than one individual. Given that the reason behind this move from the FDA is global harmonisation, it would be prudent to also look for opportunities to harmonise and consolidate processes or records if those for the US were previously kept separate from those for other markets. Consider the scope of the assessment: it needs to cover all of the quality system processes that support products being placed on the US market and/or manufactured within the US, but also consider future product launches etc. and whether other sites or processes will be affected in the future. As gaps are identified, they can be triaged in terms of the size and/or criticality of the gap to enable prioritisation at a later stage. Now it is time for the plan! How are you going to close those gaps? Who is going to close those gaps? In which order are you going to close those gaps? It is good practice to involve process owners and those with key responsibilities in determining the specifics of these actions to ensure that they are proportionate and feasible, and likely to be effective once implemented. As these efforts are aimed at addressing potential nonconformities (i.e. QMSR is not in effect yet), these efforts could be considered to be preventive actions. So whether this falls under a general quality plan, or a CAPA plan, that depends on your quality management system and/or preferences. That plan does need to include training of personnel. At a simple level, awareness of the changes and the scope of the changes for all potentially affected personnel. At a more functional level, those that are responsible for processes or tasks that are affected by the updates need to understand why the updates have occurred, and what the changes entail. And lastly effectiveness checks… Verify that all gaps had actions assigned to them. Verify that the actions have been completed as planned. Verify that the actions were effective. Audit & Inspection Readiness Two specific areas of your quality management system that will need to be thoroughly reviewed and potentially updated are internal audits and supplier management. At a simple level, references may need to be updated or removed. There may be a need for new or updated audit tools, templates and/or checklists. As described in the previous section, training of personnel is a key activity. This includes those auditors performing internal audits and supplier audits. Auditors will need to be familiar with the updated/new requirements of your processes, as well as the underlying requirements of ISO 13485:2016 and the QMSR. The changes and training need to be in place in advance of the QMSR effective date. Why? You don’t want to be facing a FDA inspection in March 2026 with an untried audit system; You need to have evidence in advance of the QMSR effective date that your changes have been successful and that procedures can be followed and implemented as intended. As discussed in the earlier section, the FDA hopes that the supply chain that supports a device manufacturer will also adopt many of the approaches required by ISO 13485:2016 and the QMSR. Whilst this is not a regulatory requirement, it is a common approach in supplier management to push quality requirements down onto suppliers to reduce the risk associated with purchases and service provision. It also helps to reduce the burden of incoming inspections and may improve the effectiveness of complaint investigations that stem from supplier issues. To improve your confidence in your compliance status and your supply chain, consider: utilising different internal auditors, or different combinations of internal auditors; bringing in third-party auditors to give a fresh perspective on things, including opportunities for improvement that are sometimes overlooked during internal audits where the focus can tend towards conformity rather than improvement. Due Diligence in Mergers & Acquisitions (M&A) No one likes nasty surprises. Transparency reduces uncertainty and helps build confidence. For those organisations looking to acquire and for those organisations hoping to be acquired, readiness for the QMSR is a key topic. When performed by either party, the gap assessment and resulting quality plans discussed above are vital if M&A activities are on your organisation’s agenda in the next two years. All parties want to understand the number, size and impact of those gaps, and the effort (and cost) to close them effectively. Being able to show potential investors or purchasers that you understand your transition towards the QMSR and have the actions under control, or have completed all the work, will be beneficial. No organisation wants to complete an acquisition and then months later be mired in quality management system remediation because of multiple 483s stemming from their establishment inspection. For smaller organisations hoping to be acquired, utilising trusted third-parties in completing or confirming your actions for transitioning to the QMSR gives greater assurance of compliance status for the acquiring company. Frequently Asked Questions What is the impact on QSIT? The FDA is in the process of developing a new inspection methodology suitable for the QMSR. The training of FDA inspectors on ISO 13485:2016 has already begun. It is possible that the new inspection methodology may be very similar to the MDSAP audit approach. The FDA will provide further guidance on this, but no specific timeframe has been given. What is the impact on FDA guidance documents that reference the QSR or specific clauses of 21 CFR 820? The FDA has stated that the change from QSR to QMSR does not substantially affect any of their existing guidance but now the final rule has been published, they will be working through implementing updates to the affected guidance. For example, the FDA’s Design Control guidance was published in 1997 and has not been updated in light of changes to ISO 13485, ISO 9001, the technological advances in the products being designed, or the introduction of software applications to aid the design and development process. The amendment to 21 CFR 820 would seem like the appropriate prompt for the Design Control guidance to be updated, especially the replacement of the terms Design Control (ISO 13485 refers to it as ‘design and development’) and Design History File. What is the impact on MDSAP? The impact is likely to be minimal in terms of the purpose of the MDSAP audits and the methodology. The changes to specific references within 21 CFR 820 will require an update to the MDSAP Audit Approach document, and with that there will be training required for the auditors at the auditing organisations. Will manufacturers get ISO 13485:2016 certification? No. The FDA will not issue ISO 13485:2016 certificates due to their inspections; they will continue to issue Establishment Inspection Reports (EIR). Third party certification to ISO 13485 is not required for compliance with the QMSR. Do manufacturers need ISO 13485:2016 certification to meet the new requirements of 21 CFR 820? No; primarily because ISO 13485:2016 on its own is insufficient to demonstrate compliance with the applicable US regulatory requirements in the QMSR and other applicable US regulations. Third party certification to ISO 13485 is not required for compliance with the QMSR. Will the FDA now accept an ISO 13485:2016 certificate as evidence of compliance with 21 CFR 820? No, as the FDA cannot guarantee that the certification body has audited against the specific US regulatory requirements: “an ISO 13485 certificate will not be considered or accepted as a substitute for any oversight processes.” What happens when/if ISO 13485 is revised? Only ISO 13485:2016 has been incorporated by reference, so the QMSR cannot automatically change if ISO 13485 is revised. The systematic review of ISO 13485:2016 is to take place at the end of 2024, so even if there is a decision to update the standard it will be several years for any revision to be published. If/when ISO 13485 is revised, the FDA will assess those changes and determine whether they want to update the QMSR or not. If they do not, it could create an odd situation, with ANSI AAMI having to publish both an outdated national standard and the national adoption of the new version of ISO 13485. The likelihood of a prolonged divergence is probably low given the FDA’s active involvement, at ISO level, in the direction and content of ISO 13485.  RQM+ Can Help Smooth Your QMSR Transition FDA Strategy and Submissions: RQM+ delivers business-balanced FDA guidance and support for medical device and IVD manufacturers across all classifications, technologies, and clinical specialties. Quality System Regulations and Standards: Regulatory requirements for quality management systems are constantly evolving, and it is up to manufacturers to stay abreast of the changes and stay compliant. The RQM+ team can help you implement best practices for keeping products and associated documentation up to date and compliant. Comprehensive Audit Programs: From internal audits to multiyear agreements auditing your entire supply chain, RQM+ has you covered. Learn all of the ways we help with auditing everywhere in the world and in any language. Acquisition Integration for Medical Devices and IVDs: Acquiring a new company or product line can have a positive business impact, but it also comes with regulatory and quality challenges. RQM+ uses a customized, business-balanced approach and proven practices to integrate new acquisitions into your quality systems. More RQM+ Resources at Your Fingertips Read our blog on Enhancing Competitiveness in MedTech: Smart Strategies with Regulatory Intelligence Register for our March Live! show: Get Ahead of the Crisis: How Your Quality System Can Prevent Negative Impacts on Customers, Patients, and Reputation Follow RQM+ on LinkedIn for all of our updates! References: 1.    The European Medical Technology Industry in figures (MedTech Europe, Oct 2023) 2.    The Pulse of Healthtech: 2023 Business Survey (ABHI & CPI, Dec 2023)3.    Challenges and Opportunities for the UK HealthTech Industry (CPI, ABHI & Catapult, Jan 2023)4.    MedTech Europe Survey Report - Analysing the Availability of Medical Devices in 2022 in Connection to the Medical Device Regulation (MDR) Implementation (MedTech Europe, Jul 2022) #### Characterizing Polymers for Novel Sustainability Initiatives Tightening environmental regulations, rising demand for circular materials, and a broader sense of ecological responsibility are just a handful of the challenges facing polymer developers today. Sophisticated polymer characterization techniques allow manufacturers to not only interrogate conventional plastics to assess their environmental impact and recycling potential, but to research and develop innovative materials that meet modern performance/sustainability demands. At Jordi Labs, an RQM+ company, we drive this effort forward by applying advanced testing methods that improve polymer recyclability, unlock biodegradable options, and support research into greener alternatives. Understanding the Sustainability Challenge in Polymer Science Traditional polymer manufacturing, which heavily relies on fossil fuels, significantly contributes to greenhouse gas emissions. Producing just one ton of polyethylene can release up to 3.2 tons of CO₂ equivalent. Furthermore, conventional polymers often persist indefinitely in ecosystems, breaking down into microplastics and infiltrating food chains, thus posing health risks to both wildlife and humans. Supply chain complexities further amplify sustainability challenges. Variability in polymer quality due to global sourcing introduces risks like contamination, inconsistent performance, and compromised recyclability. Reliable polymer characterization is essential for mitigating these risks and ensuring consistent quality and safety standards. Leveraging Advanced Polymer Characterization for Sustainability Robust characterization methods enable companies to design polymers that align environmental benefits with performance. At Jordi Labs, we use advanced analytical techniques to examine molecular structures, thermal properties, mechanical integrity, and biodegradability pathways—essential factors affecting sustainability. Molecular Weight and Structural Analysis Molecular weight distribution directly impacts a polymer's processability, recyclability, and eventual degradation. Advanced methodologies, such as mass spectrometry, facilitate precise characterization of polymer molecular structures, guiding the development of polymers designed for sustainability. Our thorough analysis enables manufacturers to choose suitable recycling methods and enhance end-of-life applications, significantly decreasing plastic waste and strengthening circular economy strategies. Thermal and Mechanical Properties Assessing thermal stability, melting points, and mechanical durability helps balance performance with environmental priorities. Jordi Labs employs melt flow analysis and rigorous mechanical testing to ensure that sustainable polymer formulations meet demanding industry standards. These tests validate material consistency and performance, enabling reliable incorporation of sustainable alternatives into high-performance applications. Biodegradability and Environmental Fate Characterizing biodegradable polymers requires an understanding of their decomposition processes in natural conditions. Our polymer chemists analyze polymer structures to identify biodegradable linkages—such as ester or amide bonds—and assess degradation rates across various environmental scenarios. This information guides the development of polymers that effectively minimize environmental impact and reduce pollution. Jordi Labs Specialized Polymer Testing Services Our comprehensive polymer testing services are designed specifically to meet the evolving demands of sustainability initiatives. Tailored Analysis for Complex Formulations Novel sustainable polymers often include proprietary additives and innovative blends, which conventional testing methods may not adequately address. At Jordi Labs, we offer customized analytical services to accurately characterize these unique formulations, ensuring that performance claims and environmental benefits are thoroughly validated. Optimizing End-of-Life Management A cornerstone of our services is enhancing polymer recyclability and end-of-life strategies. Our thorough testing identifies optimal recycling pathways, mitigates contamination risks, and improves the applicability of recycled materials. By understanding how polymers degrade under various conditions, our characterization efforts directly contribute to reducing microplastic formation and promoting safer, sustainable recycling practices. Emerging Categories of Sustainable Polymers Bio-Based and Biodegradable Polymers Bio-based polymers, derived from renewable resources, represent a rapidly growing segment in polymer sustainability. Characterizing these materials involves assessing their renewable content, structural integrity, and biodegradability. For instance, furan-based polymers derived from agricultural waste exemplify the type of innovation our advanced characterization supports, validating their performance and environmental benefits. Closing Thoughts At Jordi Labs, we understand that sophisticated polymer characterization is essential to advancing sustainability across industries. Our tailored testing services provide manufacturers with critical insights to develop and optimize sustainable polymer solutions effectively. By precisely characterizing molecular structures, thermal properties, biodegradability, and recycling potential, we help navigate the complexities of sustainability, driving progress towards a more responsible and environmentally conscious polymer industry. Contact us today if you would like to learn more. Further Reading Engineering Plastics via Gel Permeation Chromatography #### Checklist for Navigating PFAS Phase-Out in MedTech The impending phase-out of per- and polyfluoroalkyl substances (PFAS) presents a significant challenge for MedTech companies. After all, PFAS has been an integral component in manufacturing many MedTech devices.  Two key events place pressure on manufacturers to replace PFAS. The first is 3M’s decision to cease manufacturing PFAS by 2025. As 3M is one of the most significant providers of PFAS for manufacturers and suppliers, access to PFAS will become severely limited in the short term. The second event is that the EU is considering a ban on PFAS under the REACH proposal by 2030. This requires that products manufactured through the use of PFAS are removed from the EU market. To minimize business disruption, manufacturers must proactively and strategically adapt to a world without PFAS. This article shares a checklist of key considerations and steps to guide your PFAS phase-out project. These insights draw from the wealth of knowledge shared in our recent webinar on navigating PFAS challenges. Let’s start with the first step — documenting where PFAS are used.  1. Identify PFAS Usage PFAS are often employed throughout MedTech production, from core components to manufacturing aids. To effectively phase out PFAS, manufacturers must first have a clear understanding of where and how these substances are used across their product portfolio Identifying PFAS requires a comprehensive audit of the entire supply chain, scrutinizing every stage of production and every material source. This process includes: Supply Chain Collaboration — engage with your suppliers to understand the material composition and manufacturing processes of the components they provide.  Comprehensive Material Review — conduct a detailed review of all materials used in your devices. This includes active ingredients, ancillary substances, and even the materials used in packaging and shipping. Advanced Testing and Analysis — employ advanced analytical techniques to test for the presence of PFAS, particularly in cases where supplier information may be incomplete or uncertain. Documentation and Record Keeping — maintain detailed records of your findings. This documentation will aid in compliance and serve as a reference point for future product development and supply chain management. 2. Perform an Impact Assessment Once PFAS usage has been identified in your portfolio, you’re able to conduct an impact assessment to understand how phasing out PFAS will affect your products. The impact assessment is key to determining whether supplier changes are feasible or if there's a need for alternative materials and potential redesigns of your devices. An effective impact assessment will evaluate: Feasibility of Supplier Changes — whether current suppliers can provide PFAS-free alternatives that meet your quality and performance standards. This may involve exploring new supplier relationships or working with existing suppliers to develop new solutions. Alternative Materials Evaluation — if material changes are required, evaluate potential alternatives for their performance, safety, and compatibility with existing device designs. Design Modification Requirements — determine whether material changes will necessitate design alterations. Assess the scope of such modifications and their impact on device performance, safety, and effectiveness. Supply Chain Controls — revisit your controls for supplier vetting, quality agreements, and continuous monitoring. Controls need to ensure that alternative materials or supplier changes do not compromise device quality or lead to supply chain disruptions. Stakeholder Insights — the impact assessment should engage key stakeholders, including R&D, quality assurance, regulatory affairs, and procurement. Their insights will provide a holistic view of the potential implications of PFAS removal. 3. Develop a Proactive Strategy The strategy you craft to guide PFAS phase-out is vital for navigating the complex challenges of material substitution. Don’t discount this step. The more sound your strategy, the better position you’ll be in to complete the next steps in the process. As such, your strategy should encompass device performance, biological safety, and clinical evaluation.  This comprehensive strategy should prioritize maintaining or enhancing device functionality and user experience, while rigorously reassessing biological safety in line with ISO standards. Additionally, updates in clinical evaluations, including new trials or data analysis, are vital if material changes significantly alter the device. The strategy must also include detailed plans for regulatory engagement, involving cross-functional teams for a holistic approach, and implementing risk management measures to mitigate potential disruptions.  Setting clear timelines and milestones is crucial to keep progress on track. By integrating these elements, manufacturers can ensure a smooth transition from PFAS.  4. Assess the Global Competitive and Regulatory Impact Substituting PFAS materials affects how you position your products in the market and how they align with international regulatory standards.  Are there alternative materials that, for instance, provide a competitive edge? What about the effects of replacing PFAS on product certifications, labeling, and market access across the regions you operate in? With a clear, global picture of the market and the diverse requirements of different regulatory bodies, manufacturers can make informed decisions that strengthen their market position and ensure sustainable growth. 5. Materials Testing and Verification An in-depth approach to materials testing and verification is essential to securing regulatory approval and ensuring that any device modifications maintain the integrity of the final product. Testing and verification involves: Thorough Chemical Characterization — chemical analysis is needed to understand the full spectrum of chemical properties and potential interactions within the device. This characterization helps ensure the materials are PFAS-free and effective for their intended use. Verification and Validation Testing — once new materials are identified, they must undergo rigorous verification and validation testing. This process ensures that the materials meet all the necessary performance standards and regulatory requirements. It's a critical step to confirm that modified devices retain their intended functionality and efficacy. Guaranteeing Device Integrity — includes testing for durability, biocompatibility, and overall performance. Any change in materials could potentially alter the device's interaction with the body or its environment, making these tests essential for patient safety. Creating Documentation for Regulatory Compliance — all testing and validation results form a critical part of the documentation required for regulatory submissions. Ensuring these tests meet regulatory standards will streamline market approval.  6. Regulatory Documentation and Submission The final step in the PFAS phase-out process involves the meticulous preparation and submission of technical documentation to global regulatory bodies. The more effectively you execute the previous steps, the easier this process will be.  Your documents and submission strategy must be tailored to the unique requirements of the regulatory bodies you submit to. Generally, your process should include: Preparing Complete Documentation — technical documents must detail all the changes made, the results of materials testing and verification, and any other relevant data. This documentation should clearly outline the rationale behind the substitution of PFAS materials, the impact assessments conducted, and the steps taken to ensure device safety and efficacy. Effective Communication of Changes — submissions should clearly and effectively communicate all changes made to the device. This includes detailed descriptions of the new materials used, the testing processes, and the outcomes. Regulatory bodies need to understand what changes were made and why they were necessary. Clear Demonstration of Compliance — the documentation must prove compliance with the relevant regulatory standards and guidelines. This includes showing that the device meets requirements in the absence of PFAS and adheres to any new guidelines that may have been established regarding PFAS substitutes. Responding to Feedback — after submission, manufacturers need to actively monitor the review process and be ready to provide additional information or clarification as requested by regulatory bodies. Quick and effective responses can help expedite the approval process. Your Roadmap for Replacing PFAS in Your Products Successfully phasing out PFAS in medical devices is a complex but essential process. The steps shared here should help simplify your journey and ensure device safety, regulatory compliance, and market competitiveness. For more insights and tips on replacing PFAS, sign up to watch our free webinar: Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers. How RQM+ can help Comprehensive planning, strategic foresight, and extensive testing are crucial to transitioning away from PFAS.  As a full-service CRO, RQM+ has the regulatory and product testing expertise needed to streamline your PFAS journey. With decades of experience in polymers, including expertise dealing with PFAS materials, we understand the unique challenges and intricacies involved in replacing PFAS in medical devices. Speak with our experts to find out how we can support you in substituting PFAS in your products. #### Chemical Characterization Testing of Medical Devices The Food and Drug Administration (FDA) partially recognized the ISO 10993 guidance making it one of the most important for the chemical characterization testing of medical devices.1 ISO 10993 outlines all of the necessary steps for regulatory compliance to use new or existing materials in medical devices. The potential health risks from a medical device are numerous. Toxicological risk is determined by exposure time, concentration and the severity of the chemical species involved. The FDA tries to incorporate these risks into the proposed chemical characterization tests as part of ISO 10993 by insisting on different biological endpoint tests depending on where and how long a medical device will be used. The chemical characterization testing that needs to be performed for medical devices also needs to include several scenarios. This might consist of extractable testing under exaggerated use conditions or leachables testing in the types of environments the device will be exposed to in the body. It may also include chemical characterization testing for worst-case chemical release scenarios. Chemical Characterization Testing The first part of chemical characterization testing is to establish which materials will be used in a device. As ISO 10993 allows for existing safety data to be used instead for further testing when appropriate, it may be more efficient to use established materials if possible. Once the device composition is established, an assessment should be made to determine if residual risk remains. In most cases, material processing and device manufacturing introduce additional risk that new chemicals may be introduced resulting in a need for further chemical characterization testing. Then, the chemical characterization testing needs to evaluate what the worst-case chemical release scenario from a device would be. Chemical characterization testing for worst-case chemical release may also include testing for situations where the device is biodegradable or polymerizable in-situ. Extractables and Leachables At the heart of chemical characterization testing for medical devices is extractables and leachables testing. This chemical characterization testing evaluates how much and how quickly compounds can be transferred from the device into the environment. Sometimes these tests require significant sample preparation to ensure the chemical characterization testing environment is suitable to represent the use condition. Environmental conditions may also need to be adjusted to look at worst-case conditions for a device and to ensure dangerous levels of a compound are not released. One of the most critical numbers to find in chemical characterization testing is the threshold of toxicological concern. Small amounts of extractables and leachables may not pose a significant health hazard and therefore may be acceptable, but the threshold of toxicological concern must be known to determine this. With the complexity and extensive requirements for chemical characterization testing for medical devices, turn to an expert partner for help. RQM+ Lab Services are world-leaders in biological safety guidance and can advise on how to maintain the highest safety standards and achieve regulatory compliance, all without delaying the time to market for your new product. Contact RQM+ Lab Services today to find out if our chemical characterization testing could support you. FDA (2022) ISO 10993-1, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and, accessed May 2022 Further Reading: An Overview of Chemical Characterization of Medical Devices #### Christmas Tree: Artificial or Real Making the choice between a real or ‘fake’ Christmas tree can be a tough family decision.  While there are many reasons to choose artificial (no needles, doesn’t dry out, cheaper over time), possibly the best reason is safety. The National Fire Protection Association reports that, on average 230 house fires were started with Christmas trees each year, between the years of 2007 and 2011. (See source here)  There is definitely an argument to be made for the use of artificial Christmas trees, but what part of an artificial Christmas tree lends itself to its lack of flammability? https://www.youtube.com/embed/RNjO3wZDVlA?enablejsapi=1&origin=https://jordilabs.com&autoplay=0&cc_load_policy=0&iv_load_policy=1&loop=0&modestbranding=1&rel=0&fs=1&playsinline=1&autohide=2&theme=dark&color=red&controls=1& Artificial Christmas trees are polymer products (i.e. plastic) and are typically composed of polyvinyl chloride (PVC) polymeric systems. Unplasticized PVC in itself is considered to be self-extinguishing due to its high chlorine content; flammability of PVC however increases with increasing amounts of plasticizer added. PVC Christmas trees are also heavily comprised of inorganic and nonreactive organic flame retardant compounds. Among these are alumina hydrates and phosphate esters which account for nearly 45% and 15% of flame retardant compounds in plastics respectively.1  These compounds, which readily integrate into the polymer system, coactively work with the highly halogenated polymer to produce an impressively flame retardant decoration. Perhaps you may be one that enjoys the fresh pine scent of the real thing; however, if you want to be on the safe side, you may want to buy a scented plug-in and set it on high. With a diverse set of instruments, RQM+ Lab Services is equipped to provide analytical testing to qualify and quantify flame retardant compounds in your polymeric system.  Typical techniques utilized for this purpose are Pyrolysis Mass Spectroscopy (PYMS) to identify organic flame retardants and Proton Induced X-Ray Emission (PIXE) to investigate the presence of halogenated flame retardants. References:1Chemical Additives for the Plastics Industry. Radian Corporation. Noyes Data Corporation. Park Ridge, NJ. 1987 #### Classification for SARS-CoV-2: Adjusting to a Post-Pandemic Reality Under IVDR Team-NB recently released a position paper regarding the classification of devices to detect SARS-CoV-2. These devices are currently cited in the MDCG 2020-16 classification guidance as an example of a device falling under Rule 1, 2nd indent, which states: "Devices intended to be used for the following purposes are classified as class D: detection of the presence of, or exposure to, a transmissible agent that causes a life-threatening disease with a high or suspected high risk of propagation." Team-NB has outlined the factors to be considered for the classification of SARS-CoV2 according to this rule, which includes incidence, transmission, pathogenicity, mortality, and morbidity. During the SARS-CoV2 pandemic, the conditions required in Rule 1, Indent 2 for a transmissible agent at high risk of propagation as well as able to cause serious illness were met. However, since SARS-CoV2 is no longer a public health emergency, these conditions must be reassessed. The requirements to classify IVDs for SARS-CoV2 as a Class B or Class C are examined in the paper. Ultimately, Team-NB contends that these devices may be downgraded from Class D to Class C. A reclassification to Class C was endorsed rather than Class B due to the remaining risk of SARS-CoV2 for vulnerable populations. In other words, the transmissible agent could still result in life threatening illness for certain populations and therefore, rule 3c applies (detecting the presence of an infectious agent, if there is a significant risk that an erroneous result would cause death or severe disability to the individual, fetus or embryo being tested, or to the individual's offspring). The ability to adjust the list of high-risk agents makes sense when considering the wording of the rule itself. If a new infectious disease with a suspected high risk of propagation emerges, it can fall under rule 1 until a time when the scientific evidence has shown it no longer meets both requirements. Under a similar rationale, agents that were once at a high risk of propagation and/or causing life threatening illness, may be downgraded once the pandemic is under control, as is being suggested for SARS-COV2. In fact, it is incorporated directly into the guidance MDCG 2020-16. A note is included under Rule 1, 2nd indent indicating that the list of high-risk agents may be updated based on new scientific data. However, there has yet to be an example of this type of classification change. An update to the guidance to align with the Team-NB position would be the first of its kind under IVDR. This Team-NB paper puts into writing a topic that has been on the minds of stakeholders in the IVD industry for many months and provides a rationale for adjustment of the classification for SARS-CoV2 devices. Many people in the industry have been having discussions on this very topic and wondering if there is an opportunity for a change of classification and an easier path to the EU market for SARS-CoV2 devices.  The Team-NB paper opens a door that could have far reaching benefits for manufacturers, notified bodies, and ultimately patients by reducing the barriers to market for the devices in the EU. While there is a pathway for change based on the language in IVDR Annex XIII classification rules as well as the MDCG 2020-16 classification guidance, there are many considerations and complexities in the practical implementation of this change. It is likely that with the release of the Team-NB paper, notified bodies are already thinking ahead to these factors (even if only abstractly). The following must be considered for key stakeholders to appropriately respond to any changes in classification of SARS-CoV2 IVDs. 1. Legal Manufacturer Adjustments Legal manufacturers will need to update SARS-CoV2 technical files to reflect the classification change. This activity could become quite complex depending on where in the IVDR transition process they are.  Other documents may also be impacted and require updates. For example, procedures that specifically mention Class D requirements need to be assessed.  2. Notified Body Considerations Many of the consequences of this change will fall on notified bodies to sort out. Notified body certification schemes are different for Class D versus Class C/B devices. Class D devices require technical documentation assessment certificates whereas Class C devices (that are not Near patient tests or self-tests) are covered under a quality management system certificate and devices on these certificates are placed into generic device groups based on intended use and technology. How will this be managed if these IVDs are downgraded? Will any issued Class D technical documentation assessment certificates be cancelled or voided? Similar questions exist for devices currently undergoing conformity assessment. What happens with the ongoing technical reviews for SARs-Cov2 assays? Will the manufacturer be required to update technical documents to reflect the new classification before the review can continue? If the device falls into a group that is already certified, then what happens with the ongoing review? There are also questions in regards to batch release. Class D devices require batch release by the notified body and are expected to be subject to testing by European Reference Laboratories (EURLs) by the end of 2024. For any devices certified before a classification change is made, how would these devices be transitioned away from batch release requirements? We must also consider the potential upside for notified bodies. A reduction in classification from Class D to Class C will free up valuable resources to continue working on the IVDR transition. Since all Class D devices require technical review, the total number of technical reviews will ultimately decrease as SARS-CoV2 IVDs will be sampled as part of the generic device group. In addition, notified bodies will not have to allocate resources to batch review or to PSUR review for these IVDs once they are certified.  3. Common Specifications Reevaluation The common specifications for SARS-CoV2 IVDs must also be considered. The Implementing Regulation (EU) 2022/1107 for common specifications is specifically applicable for class D devices. What is the applicability of the common specifications in the event that COVID assays are downgraded to class C? Will the implementing regulation be updated to remove SARS-COV-2, or will they be updated to remove the Class D specificity currently within the document? Will there still an expectation that they be followed as this is now considered state-of-the-art? This is an especially important question for manufacturers who may have devices in product development, especially those planning and executing clinical trials for a SARS-CoV2 IVD. 4. Classification Update Process A change in classification of SARS-CoV2 and potentially other analytes in the future, is likely to be triggered through an update to the MDCG 2020-16 classification guidance. However, the process to update this document and then introduce these changes throughout the notified bodies takes time. In the event that SARS-CoV2 (or other pathogens) must be up-classified back to Class D, can the system respond with haste to ensure patient safety. All of the concerns cited above become even more relevant but in reverse.  Conclusion and stay updated with rqm+ The Team-NB position paper outlines a pathway that would reduce regulatory burden for manufacturers of SARS-CoV2 devices and alleviate some burden on notified bodies, but there are still many practical considerations that will be triggered if it is brought to fruition. RQM+ will continue to watch this space closely, and continue to update, analyze, and provide guidance to stakeholders for any future updates on this topic.  Keep up to date: Follow RQM+ on LinkedIn Subscribe to our blog Subscribe to the RQM+ Device Advice podcast  #### Code Red: How Reimbursement Fails MedTech’s Best and Brightest Why Did the MedTech Innovator Go Broke?  You’ve built a life-saving medical device designed to revolutionize healthcare. But here’s the catch: without reimbursement, it’s a Ferrari without fuel. It’s like cooking a Michelin-star meal for diners stranded on a cashless desert island: brilliant but inaccessible. Welcome to the wild world of MedTech, where groundbreaking innovation meets bureaucratic hurdles. From my adventures in cardiovascular R&D to untangling regulatory mazes in the EU as a regulator, I’ve seen how reimbursement can turn a moonshot into a mayday. Innovating in MedTech is like being on a strict diet: You have all these amazing ideas, but regulators keep counting your calories! Let’s explore RQM+’s playbook to conquer reimbursement, where precision meets ingenuity, and brilliance outmaneuvers bureaucracy. FDA’s Green Light, CMS’s Brick Wall: Navigating MedTech’s Hunger Games The FDA’s Breakthrough Device Program aims to incentivize innovation, but is it enough to guarantee success? Sure, it prioritizes technologies addressing unmet needs, but approval only gets you to the starting line. Regulatory approval ≠ market success. Imagine your device earns the FDA’s laurels only to face a Centers for Medicare & Medicaid Services (CMS) shrug and insurers playing hardball. These payers demand clinical and economic proof like it’s the elixir of success, except proving it shouldn’t require a 500-page dossier. Legislative lifelines like the proposed H.R. 1691 bill aim to toss innovators a provisional reimbursement buoy while they gather evidence. But navigating this will require the finesse of a tightrope walker balancing on a regulatory razor. At RQM+, we turn “no guarantee” into “no problem,” aligning regulatory and reimbursement strategies with surgical precision. Drug-Coated Balloons vs. Payer Apathy: A $10B Standoff Drug-coated balloons (DCBs) promised a revolution but met a roadblock: payers snoozing while hospitals foot the bill. Compare this to drug-eluting stents (DES) or intravascular lithotripsy (IVL), and the reimbursement gaps glare like a neon sign in a blackout. A Payer’s Favorite Horror Movie? "Nightmare on Evidence Street"It’s where good claims go to get buried. Digital Health in Chains: CMS Is Stalling the Future of Care Digital health? It’s the iPhone of healthcare, transformative, yet stuck in 2007 without the App Store. CMS’s exclusion of digital health from benefit categories is like banning solar panels to save the candle industry. Mustn’t we decide whether to fund the future or fossilize? Global evidence screams efficacy, yet we remain tethered to outdated frameworks. At RQM+, we don’t just highlight these disparities, we dismantle them turning stagnation into progress. FDA vs. CMS: Crafting Evidence That Both Agencies Will Swallow Whole One of the most significant challenges in MedTech development lies in aligning the clinical evidence required for FDA approval with the evidence demanded for reimbursement by CMS and payers. The refrain “We don’t know what CMS wants” isn’t a knowledge gap, it’s a planning pitfall, a missed opportunity. Designing trials without CMS input is like writing a symphony for an audience that can’t hear. Harmonized trials aren’t optional: they’re survival. Why are medical device regulators considered athletes? …because they're always setting high bars and performing regulatory gymnastics! Real-World Evidence: CSI for Payers (Hint: The Killer Is Bad Data) Real-world evidence (RWE) is your Sherlock Holmes, but sloppy data won’t pass regulatory muster and will sink even the best innovations. At RQM+, we orchestrate trials that hit every note, from early CMS courtship to RWE that’s more bulletproof than Fort Knox. Pricing’s High-Wire Act: Avoiding MedTech’s Icarus Moment (Spoiler: Balance Over Greed) Innovation comes at a cost, but here’s the reality: price ≠ value. Success lies in proving your device’s long-term worth: Cost-Effectiveness Studies: Transform “too expensive” into “can’t afford not to.” Prove your device slashes hospital stays and long-term costs, turning payers into advocates. Balanced Pricing Strategies: Strike the perfect balance between ambition and accessibility. Think Goldilocks: not too greedy, not too modest. Nail the sweet spot that’s compelling and competitive. Investing in medical devices is like buying weather forecasts; both promise sunny days but prepare you for possible storms. At RQM+, we help ensure your tech isn’t just innovative – it’s positioned to secure reimbursement and deliver lasting impact. Medicare’s Blind Spot: Ignoring Comorbidities Is a Recipe for Failure Homogeneous trials are MedTech’s original sin. Diversity in trials isn’t a checkbox exercise, it’s a moral and strategic imperative. Medicare patients are walking Venn diagrams of complexity. Trial designs that ignore them are like selling snow boots in a desert. Medical device reimbursement is like modern dating; both require extensive evidence you’re worth the investment, and ghosting is still an issue. Medical device reimbursement demands extensive evidence of value—and, yes, ghosting is still an issue. We engineer trials as diverse as humanity itself at RQM+, because innovation that excludes is innovation that fails. NTAP: CMS’s Participation Trophy - Why MedTech Needs More Than a Gold Star Programs like CMS’s New Technology Add-On Payment (NTAP) offer temporary support but often fall short of ensuring sustained adoption. In reality, temporary fixes like NTAP are Band-Aids on bullet wounds. The need of the hour is sustained solutions with teeth and data so compelling, even uncle Scrooge would sign off. RQM+ doesn’t just navigate these complexities, we rewrite the playbook, turning payer skepticism into standing ovations. Regulatory Jiu Jitsu: How to Punch Through Bureaucracy Without Breaking a Sweat Reimbursement is the ultimate battleground in MedTech and winning requires agility, strategy, and precision. Here’s how to dodge bureaucracy’s pitfalls and deliver results: Early CMS Involvement (CMS at Dawn: Why Latecomers Lose the Reimbursement War):Forget regulatory roulette, aligning trial designs with FDA and CMS playbooks from day one ensures no surprises. Early CMS involvement is your prenup with payers: clear terms, no messy divorces. With synchronized strategies, you’ll deliver slam-dunk evidence that satisfies both regulators. Joint FDA-CMS Trials (FDA + CMS = Regulatory Avengers):Why play tag with two agencies when you can unite FDA rigor with CMS pragmatism? Harmonizing requirements creates a trials tango with no missteps, just market-ready momentum. Think of it as a regulatory power couple rewriting the rules of engagement, transforming complexity into competitive advantage. Transparent Guidelines (Decoding CMS’s Rosetta Stone):Turn CMS’s cryptic rulebook into a precision-engineered roadmap. Everyone wins when the finish line isn’t a mystery. Bonus? Crack the reimbursement (Da Vinci) code and let your device shine. RWE Standards (Data So Bulletproof It’s Unstoppable):Real-world evidence (RWE) is the backbone of long-term success but it must be robust enough for CMS to build skyscrapers on. No coffee-stained spreadsheets here, just regulatory-grade gold that transforms skepticism into confidence. Short-Term Payments (Cash Infusions for Innovators):Ramen noodles won’t fund clinical trials. Financial bridge loans can keep innovation afloat in the purgatory of evidence development. It’s venture capital meets public health: fuel your R&D engine while your data catches up. Coverage with Evidence Development (CED: The Ultimate ‘Try Before You Buy’):CED allows provisional access to new technologies while gathering real-world proof of effectiveness. Patients get hope, payers get data, and you get a foot in the door. It’s science as your sales pitch; no gimmicks, just results. Cost-Effectiveness Studies (Turning ‘Too Expensive’ Into ‘Can’t Afford Not To’):Demonstrate that your tech isn’t a cost; it’s a cure for bloated budgets. Think solar panels for healthcare, pricey upfront but shining savings brighter than an OR light. Balanced Pricing Strategies (The Pricing Trilemma):Walk the tightrope where greed kills adoption, and meekness destroys ROI. Nail the perfect trapeze landing with mathematics, strategy, and a dash of Machiavelli. Addressing Disparities (Healthcare Deserts vs. Innovation Oases):Innovation isn’t just a product, it’s a promise. Bridge access gaps before your tech becomes another ‘could’ve been.’ Equality isn’t a buzzword; it’s a business model for sustainable success. Public Engagement (Crowdsourcing the Future):Turn guidance documents into crowd-sourced masterpieces. Protocols shouldn’t live in a bubble; healthcare’s future should be a democracy, not a dictatorship. Policy Changes (Reimbursement 2.0):Say goodbye to dial-up frameworks and hello to 5G innovation. It’s time to swap outdated reimbursement relics for 21st-century speed and agility. If healthcare were a smartphone, we’re overdue for a software update. From Rubik’s Cube to GPS: How RQM+ Turns Reimbursement Hell into a Highway Navigating MedTech reimbursement is like solving a Rubik’s Cube blindfolded in a hurricane. At RQM+, we turn chaos into clarity, barriers into breakthroughs, and skeptics into believers. We’re not just consultants; we’re co-conspirators in your revolution. Whether you’re a scrappy startup or a MedTech giant, RQM+ ensures your vision doesn’t just survive, it thrives. Let’s redefine what’s possible in MedTech innovation. Your next favorite resource from this author: Download the white paper, "Trials That Pay: Designing Clinical Studies to Optimize Reimbursement and Market Access". Further reading - Breaking New Ground: Introducing the Transitional Coverage for Emerging Technologies (TCET) Pathway #### Common Causes of Polymer Failure Understanding how and why materials degrade and ultimately fail is a critical step in the research and development (R&D) process. Compared to the lifespan of traditional engineering materials, polymers tend to fail in comparatively short timeframes. It is one of the reasons that polymers like high- and low-density polyethylene (HDPE/LDPE), or polyethylene terephthalate (PET) are widely used as single-use plastics. Polymer failure is dynamic and has extremely complex mechanisms that may occur due to inherent chemical and structural deficiencies in the product, or as a result of adverse external factors. It matters less in the context of single- and few use plastics than in the likes of permanent polymeric products, where premature failure can lead to liability issues or even injury. This refers to products as varied as polymeric fibers, films, membranes, engineering plastics, and more. In this article, we will be considering some of the common causes of polymer failure that forensic analysts typically screen for. Mechanical Polymer Failure Mechanical modes of polymer failure are extremely varied and may occur at stress levels below the ultimate tensile strength (UTS) of the product. Creep rupture, also known as long-term stress, is a measure of time-dependent deformation under constant load. This can result in gradual deformation by sustained albeit low loads. Fatigue, or cyclic loading, promotes a similar type of gradual failure via slow crack growth. Other mechanical modes of polymer failure include brittle and ductile fracture, rapid fracture due to impacts, and wear due to surface abrasion. Thermal Polymer Failure Temperature changes can have a dramatic influence on polymer failure, by accelerating chemical or mechanical modes, or by thermally-inducing degradation. Cyclic heating and cooling can cause thermal fatigue in polymeric materials which contribute to macroscopic crack growth and structural distortion. Irreversible dimensional instability can be caused by single instances of high peak temperatures, which may be characterized by depolymerization, shrinking, swelling, or more. Other, more severe, forms of thermal polymer failure include combustion and direct flame impingement. Chemical Polymer Failure Chemical attack, more so than many other modes of polymer failure, is largely determined by the material’s application area. Interactions between polymeric materials and a limitless range of chemicals can cause some form of degradation or strain. Polymers intended for use outdoors will have to withstand oxidation and exposure to ultraviolet light. Hydrolysis can also cause failure when molecules from water, acids, or alkalis rupture the chemical bonds of polymeric materials. Other modes of chemical polymer failure include stress corrosion cracking (SCC), but this mechanism is incredibly broad, owing to the impossibly large number of combinations of chemical interactions between corrosives and polymers. This is common in applications where polymers come in contact with cleaning agents. Polymer Failure Analysis with RQM+ Lab Services RQM+ Lab Services is one of the US’s foremost polymer failure analysis laboratories, with an experienced team of Ph.D. chemists who are well-versed in the various modes of polymer failure that can affect your products. Alongside the above, we can also screen for more complex modes of failure, such as ultraviolet degradation (optical) and molded-in stress (polymer processing defects). For more information, simply contact a member of the RQM+ Lab Service team today. #### Contaminant Analysis: How to Interpret Particulate Matter Particulate contamination analysis using microscopy and spectroscopy methods can identify and mitigate contamination in chemical, consumer products, industry or processes. Particulate analysis is the first stage in resolving contamination issues that could be potentially critical. These issues can take place at many points through the supply chain of numerous industries. Particulate contamination identification means that action can be taken to mitigate and prevent further or additional contamination. How does Particulate Contamination Work? Particulate contamination investigations involve identifying microscopic particles, the isolation of various particulate phases of in-homogenous production deposits and determining the source of the contaminants. Mitigating particulate contamination can be done by identifying contaminants through expertise in sampling and sample preparation, chemical identification, physical/visual examination and root cause analysis. Contaminant particles can be digitally imaged using microscopy to offer forensic traceability. Once the initial microscopical assessment has been carried out, analysis can be undertaken using energy-dispersive X-ray spectroscopy on isolated particles with scanning electron microscopy (SEM) or vibrational spectroscopy. Characterization of the shape or size of particulate contamination can be carried out using photomicrography. Examples of how Particulate Contamination Analysis can be Used: Identifying metal abrasion and corrosions which has caused extraneous metal particles from pipes, pumps, etc. to be present in water. Identifying residual particles from cleaning and maintenance Identifying mineral particles when the manufacturing or geographic origin is of particular importance. Finding glass fragments caused by breakages. When particle contaminations are present in valuable samples such as medical devices and pharmaceuticals, the impact is extremely far reaching. These types of particle contaminations can create inefficiencies, delays in delivery and compromised product quality for the consumer and patients. These particulate contaminations can be caused by a range or sources such as packaging, undissolved residuals in buffer and media solutions, and a range of system components like gaskets and seals. Particulate contamination can also be a result of side reactions associated with the manufacture of the product, such as charred products and detergent residues or due to degradation or maintenance of the processing equipment such as lubricant oils, metal corrosion and Teflon gasket scoring. Particulate contamination can spread to the air volume of a clean room in close proximity via airborne contamination or transport of people or containers. This can then cause contamination of both products as well as the manufacturing area. These particles can have negative effects if carried over to the final drug product including microcirculation, blockages of blood vessels, impairment, and organ damage. Identifying and considering the source of particulate contamination is critical to controlling their spread. Once the source is identified, the removal of the particulate contamination becomes considerably simpler. At RQM+ Lab Services, we use FTIR-microscopy, SEM-EDX along with other methods of identifying particulate contamination and we are able to provide information about shape, size and surface topography. To find out more, contact us today. #### Contamination Detection: Particulates and Residue Analysis with RQM+ Lab Services Process and quality control in the pharmaceutical industry requires highly-discerning contaminant detection, including particulates and residue analysis. These elements are among the primary forms of contamination in the pharmacological industry, and can arise from a broad range of sources including polymer blister packets, undissolved residuals in media or buffer solutions, or metallic manufacturing components such as oven gaskets. Particulates and residue can compromise pharmaceuticals at any stage of manufacturing, from primary and secondary formulation, to packaging and transportation. In the formation stages, particulates and residue contamination can occur due to cross-reactions with manufacturing media. Excipient materials and active ingredients (AIs) can react with mechanic residue such as oils or lubricants. Machinery degradation or maintenance chemicals can also affect the chemical composition of pharmaceutical compounds. Corroded metals or deteriorating fluoropolymer gaskets can deposit significant volumes of particulates and residues, particularly during thermal processing of pharmaceutical ingredients. Typical particulates and residues discovered in pharmaceuticals include glass; aluminum; polymers; rubber; and wood. These often enter the product through clean room environments, in which the air volume has been compromised by unsatisfactory sanitization. Particulates and residue can be transported into these atmospheres by containers or clinicians. The danger of particulates and residues being carried through formulation to the dosage form product or entering the material during the latter stages of production is significant. For example, consumers can experience impaired circulation, with particulates and residues blocking blood vessels and causing damage to their organs. The Importance of Particulates and Residue Analysis Particulates and residue analysis is critical for characterizing pharmaceutical contaminants, how they enter the manufacturing process, and the way they perpetuate within the product. Identifying the source of contamination is the primary concern for clinicians and analysts performing particulates and residue characterization. Microscopy is a common methodology for determining the composition of a particulate or residue in a control sample, and determining the genesis of a contaminating substance within a product. FTIR-Microscopy is used to analyze the heterogeneity of a sample and screen for unknown particles at scales as low as 10 – 15 micrometers (µm), providing accurate chemical composition characterizations to detect the presence of organic particulates. Scanning electron microscopy (SEM) is also used to distinguish particulates and residue in a sample using a scanning electron beam and a sensitive x-ray detector for acquiring the x-ray emission spectra from particles within the sample. This is used to identify the surface topography and elemental composition of a sample, and to identify undesirable particulates with detection limits of 1,000 – 3,000 parts per million (ppm). Particulates and Residue Analysis with RQM+ Lab Services Labs At RQM+ Lab Services, we apply our expertise to the assessment of pharmaceutical products to identify the origin of particulates and residues in failed batches and for quality control processes. We operate with leading equipment and professionalism to ensure that your products and processes fit the stringent compliances of the pharmaceutical sector. If you would like any more information about performing particulates and residue analysis with RQM+ Lab Services, please do not hesitate to contact us. #### Defining Usability Objectives If you ever plan usability testing activities for a medical device, you may find yourself responsible for defining usability objectives. Today’s topic is - What makes a good usability objective? Usability objectives (or requirements) are typically driven by either safety concerns or business goals. Safety related objectives should originate from the risk management process and are designed to show that risk mitigations are effective. Business related objectives usually come from market research – what the customers are looking for and what the competition currently offers. The most effective usability objectives contain several key elements: Task – including a quantitative goal so that success can be easily defined, usually in terms of time, accuracy, task completion rate, etc. The highest risk tasks and the most important tasks for using the device effectively should be included when defining tasks. User profile – specific user group that will perform the task. Use environment – context of device use for a particular task, including physical and social environmental factors. Use environment is not always specifically called out in the usability objective but is often implied. It should, at a minimum, be defined for the device in the usability documentation and considered when developing usability objectives. As much as possible, objective (performance based) tests should be used to evaluate usability objectives, especially those related to the safety of the device. Subjective (often preference based) tests may also be used but are somewhat arbitrary and should be used in addition to, rather than in place of, performance tests whenever possible. Both forms of feedback can be valuable and should be considered when developing usability objectives. Here are some examples of well-defined usability objectives. See if you can guess which ones are motivated by safety concerns or business goals, and whether they require performance testing or preference testing. (Answers are at the bottom of the post – No cheating!) 1. “90% of experienced* technicians shall be able to set up the system for use in a laboratory setting within 3 minutes.” 2. “80% of experienced* ICU nurses shall prefer the user interface of this infusion pump to that of their existing infusion pumps.” 3. “100% of trained** surgeons shall be able to correctly connect the device tubing to the patient cannula without visibly introducing air into the circuit.” *Level of experience could be quantified by a knowledge test or by simply asking how many years of experience a user has. **Training should be controlled and consistent across users. You might think – Those usability objectives are nice, but where do those percentages come from? How do I define acceptance criteria for my objectives? – Check in next Wednesday to find out! In the meantime, if you define usability objectives differently let's talk about it! -KB 1. Business, performance. 2. Business, preference. 3. Safety, performance. #### Determining the Primary Endpoint in Clinical Research The purpose of clinical studies is to scientifically address an unmet clinical or regulatory need in the treatment of patients. Informing clinical practice and policy, the outcomes ultimately aim to improve health care. Working in a client centric manner, RQM+ helps navigate important trial nomenclature within your intended clinical investigation. This piece is concerned with explaining what a primary endpoint is and taking you through the thoughts that define a good primary endpoint.  Definition and purpose  The outcome measure that answers the reason for conducting a study is the primary endpoint. The term endpoint is distinct from the use of the term in animal research, where it describes the point at which to ethically end the study for the individual experimental animal. In clinical research, the primary endpoint operationalizes the design of the study and determines the meaningfulness of the study for policymakers (McLeod et al., 2019). The primary endpoint translates the study´s hypothesis into a measurable, treatment-relevant entity and is defined prior to the start of study.  Its discriminatory reflection of the allocated treatment is seen as the sine qua non to assign success to the conduct of a study. However, this assumes a sufficiently powered study (Pocock and Stone, 2016). Surrogacy and compositeness of primary endpoints may be required to adequately depict realistically achievable outcomes in a trial or investigation (Weintraub et al., 2015; Gómez et al., 2014; Pocock et al., 2015). The statistics and medical writing team at RQM+ can advise on these issues.  Descriptors of a primary endpoint The primary endpoint can be developed using SMART categories (Purna Singh et al., 2022) and characteristically is all of the following: sensitive to change, clinically relevant, measurable using a validated method, of limited variability in the population of interest, objective, achievable at the timepoint of collecting relevant data. The selection of a primary endpoint is typically clinician driven but adequately trained staff at RQM+ (medicine & science) will be able to assist in your deliberations. The target outcome may be replaced by a linked intermediate outcome, termed surrogate.  Careful consideration is required to demonstrate alignment of the surrogate parameter with the primary endpoint and justify its patient-relevant meaningfulness (Ciani et al., 2023).  A primary endpoint should be complemented by patients´ own assessments of health-related quality of life in the shape of patient reported outcomes as a secondary endpoint (Pavlovic et al., 2014; Andrade, 2015). Efforts to standardize patient reported outcomes are increasingly being made and should be included where possible (e.g., Coens et al., 2020; Tong et al., 2022). RQM+ will research developments in your therapeutic area for you. Watch now ▶ Advancing Health Equity with IVDs & Medical Devices Standardized definitions of endpoints  In the interest of comparative meaningfulness of the outcomes of clinical studies, endpoints are being more accurately defined to effect precision-guided adaptation of clinical practice (e.g., Reddel et al., 2009; Buggy et al., 2018; Hicks et al., 2018; Kilickap et al., 2018; Battelino et al., 2023). It is important to use these definitions as they become available to allow accelerated compilation of evidence of treatment from randomized controlled trials and ideally from complementable outcomes of real-world evidence studies (LoCasale et al., 2021). Where subjective endpoints are standardisable using patient reported outcomes, patient engagement and involvement in clinical research may be increased (Myles et al., 2018). Staying abreast of these technical developments is a key remit of RQM+'s medical writing team, which you will directly benefit from when engaging with us. Endpoint adjudication Sometimes, subjective evaluations are needed to decide whether the clinical event corresponds to the attainment of the primary endpoint (Seltzer et al., 2017; Facile et al., 2022). Then, clinical endpoint adjudication by an independent Endpoint Adjudication Committee in clinical trials may become necessary. Clinical Research Organizations have formulated a statement on the independence of such committees where they are necessary (Spitzer et al., 2022) and RQM+ will refer to this. Sample size calculation Definition of the endpoint informs the sample size, meaning that the sample size is calculated based on the endpoint and assumptions made that relate to the variation in the intended study population. Secondary endpoints, by contrast, do not input in the sample size calculation but are designed to generate evidence that is supportive of the primary endpoint (McLeod et al., 2019). This is why patients' own assessment of their quality-of-life works best as a secondary endpoint to the investigation. Of note, the size of the sample depends not only on the variability of the outcome measure. It is also influenced by the effect size (or minimal clinically relevant difference), the power of the study and p-value (Gupta et al., 2016), typically draws on similar previous studies for the event rate and includes inflation by an estimated dropout rate (Kadam and Bhalerao, 2010). The medical writing team at RQM+ will assist you in identifying relevant key references for your intended investigation. We will also research for you the dropout rate for your envisaged patient population, duration, and type of intervention and discuss with you the possibility of conducting an interim analysis. When pre-specified, an interim analysis may yield an adjustment of the sample size (Ciolino et al., 2023) and inform you early of the likely success of your investigation as planned. A statistical analysis plan operationalizes the analytical approach and statistical methodology (Stevens et al., 2023) and is drafted by RQM+ according to your study specifics.   Also from this author 📄 The German DiGA (Digital Health Applications) Idea Analysis of potential covariates When the primary endpoint is chosen, it is important to consider so-called baseline covariates: these are variables which have or may have an association with your chosen primary outcome measure. Adjustment for these covariates improves the efficiency of the analysis because it avoids a conditional bias from chance covariate imbalance (EMA, 2013). This statistical adjustment needs to be prespecified (Pocock and Stone, 2016) and is routine to RQM+'s statisticians. Randomization is thought to lead to a balancing of potential confounders (given a large enough sample size), allowing causal inference of a treatment effect.  However, typically, rather than balancing confounders, randomization seeks to ensure an even distribution of potential confounding causes. The concept of confounding causes rather than confounding factors is fundamentally important because it also influences how we think about a possible selection bias in observational studies (Fuller, 2019). Conclusion When conducting a clinical investigation, standards within the normative framework (regulations and ethics) of designing, conducting, and reporting clinical studies must be followed. The primary endpoint measures the primary outcome of a study and may map to one of several categories: safety, effectiveness/efficacy, performance (clinical/technical), clinical benefit. Its choice and attainment are relevant to treatment, health care policy and/or regulatory approval. Regulatory bodies may themselves shape the suitability of surrogate endpoints (Kordecka et al., 2019). Policymakers, however, are but one group of stakeholders in clinical studies. It is viewed as desirable by clinicians that patients themselves input into the meaningfulness of primary endpoints through their representations (Bundgaard et al., 2022). In fact, more recently, participants in clinical research are appreciated as emancipated partners who inform study design and feasibility and whose data contribute to answering health care questions (Faulkner et al., 2023).  RQM+ can advise on these novel aspects. Compositeness of primary endpoints is viewed critically generally and by RQM+ because composite primary endpoints are seldom in equipoise in terms of severity, frequency, and importance to the patient (Palileo-Villanueva and Dans, 2020). Secondary endpoints, however, are valuable as supportive, additional measures of relevance to the primary endpoint (Vetter and Mascha, 2017) and you may tap into RQM+'s ample experience across many therapeutic areas.  Stay tuned next week for our technical brief on, "Insight into RQM+ Consultation: How the most appropriate study design is determined." Subscribe to our blog to be notified when it is published! Download your copy 📄 Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation References Andrade C. The primary outcome measure and its importance in clinical trials. J Clin Psychiatry. 2015; 76(10):e1320-3. doi: 10.4088/JCP.15f10377. Battelino T, Alexander CM, Amiel SA, Arreaza-Rubin G, Beck RW et al. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol. 2023; 11(1):42-57. doi: 10.1016/S2213-8587(22)00319-9. Buggy DJ, Freeman J, Johnson MZ, Leslie K, Riedel B et al.; StEP-COMPAC Group. Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes. Br J Anaesth. 2018; 121(1):38-44. doi: 10.1016/j.bja.2018.03.020. Bundgaard JS, Iversen K, Bundgaard H. Patient-prioritized primary endpoints in clinical trials. Scand Cardiovasc J. 2022; 56(1):4-5. doi: 10.1080/14017431.2022.2035808. Ciani O, Manyara AM, Davies P, Stewart D, Weir CJ et al. A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials. EClinicalMedicine. 2023; 65:102283. doi: 10.1016/j.eclinm.2023.102283. Ciolino JD, Kaizer AM, Bonner LB. Guidance on interim analysis methods in clinical trials. J Clin Transl Sci. 2023; 7(1):e124. doi: 10.1017/cts.2023.552. Coens C, Pe M, Dueck AC, Sloan J, Basch E et al; Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium. Lancet Oncol. 2020;21(2):e83-e96. doi: 10.1016/S1470-2045(19)30790-9. Facile A, Mewton N, Nguon M, Durand de Gevigney G, Grinberg D et al. Primary endpoint adjudication: comparison between the expert committee and the regulatory MedDRA® coding in the MITRA-FR study. Eur J Heart Fail. 2022;24(2):396-398. doi: 10.1002/ejhf.2401. Faulkner SD, Somers F, Boudes M, Nafria B, Robinson P. Using Patient Perspectives to Inform Better Clinical Trial Design and Conduct: Current Trends and Future Directions. Pharmaceut Med. 2023; 37(2):129-138. doi: 10.1007/s40290-022-00458-4. Fuller J. The Confounding Question of Confounding Causes in Randomized Trials. Br J Philos Sci. 2019;70(3):901-926. doi: 10.1093/bjps/axx015. Gómez G, Gómez-Mateu M, Dafni U. Informed choice of composite end points in cardiovascular trials. Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):170-8. doi: 10.1161/CIRCOUTCOMES. 113.000149. Gupta KK, Attri JP, Singh A, Kaur H, Kaur G. Basic concepts for sample size calculation: Critical step for any clinical trials! Saudi J Anaesth. 2016;10(3):328-31. doi: 10.4103/1658-354X.174918. Hicks KA, Mahaffey KW, Mehran R, Nissen SE, Wiviott SD et al.; Standardized Data Collection for Cardiovascular Trials Initiative (SCTI). 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials. Circulation. 2018;137(9):961-972. doi: 10.1161/CIRCULATIONAHA.117.033502. Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res. 2010; 1(1):55-7. doi: 10.4103/0974-7788.59946. Kilickap S, Demirci U, Karadurmus N, Dogan M, Akinci B, Sendur MAN. Endpoints in oncology clinical trials. J BUON. 2018;23(7):1-6. Kordecka A, Walkiewicz-Żarek E, Łapa J, Sadowska E, Kordecki M. Selection of Endpoints in Clinical Trials: Trends in European Marketing Authorization Practice in Oncological Indications. Value Health. 2019;22(8):884-890. doi: 10.1016/j.jval.2019.03.007. LoCasale RJ, Pashos CL, Gutierrez B, Dreyer NA, Collins T et al. Bridging the Gap Between RCTs and RWE Through Endpoint Selection. Ther Innov Regul Sci. 2021;55(1):90-96. doi: 10.1007/s43441-020-00193-5. McLeod C, Norman R, Litton E, Saville BR, Webb S, Snelling TL. Choosing primary endpoints for clinical trials of health care interventions. Contemp Clin Trials Commun. 2019; 16:100486. doi: 10.1016/j.conctc.2019.100486. Myles PS, Boney O, Botti M, Cyna AM, Gan TJ et al; StEP–COMPAC Group; Myles P, Grocott M, Biccard B, Blazeby J, Boney O, Chan M, Diouf E, Fleisher L, Kalkman C, Kurz A, Moonesinghe R, Wijeysundera D. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort. Br J Anaesth. 2018;120(4):705-711. doi: 10.1016/j.bja.2017.12.037. Palileo-Villanueva LM, Dans AL. Composite endpoints. J Clin Epidemiol. 2020;128:157-158. doi: 10.1016/j.jclinepi.2020.07.017. Pavlovic M, Teljeur C, Wieseler B, Klemp M, Cleemput I, Neyt M. Endpoints for relative effectiveness assessment (REA) of pharmaceuticals. Int J Technol Assess Health Care. 2014;30(5):508-13. doi: 10.1017/S0266462314000592. Pocock SJ, Stone GW. The Primary Outcome Fails - What Next? N Engl J Med. 2016;375(9):861-70. doi: 10.1056/NEJMra1510064. Pocock SJ, Clayton TC, Stone GW. Design of Major Randomized Trials: Part 3 of a 4-Part Series on Statistics for Clinical Trials. J Am Coll Cardiol. 2015;66(24):2757-2766. doi: 10.1016/j.jacc.2015.10.036. Purna Singh A, Shahapur PR, Vadakedath S, Bharadwaj VG, Kumar DP, Pinnelli VB, Godishala V, Kandi V. Research Question, Objectives, and Endpoints in Clinical and Oncological Research: A Comprehensive Review. Cureus. 2022; 14(9):e29575. doi: 10.7759/cureus.29575. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA et al.; American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99. doi: 10.1164/rccm.200801-060ST. Seltzer JH, Heise T, Carson P, Canos D, Hiatt JC, et al. Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium. Am Heart J. 2017; 190:76-85. doi: 10.1016/j.ahj.2017.05.009. Spitzer E, Fanaroff AC, Gibson CM, Seltzer J, McFadden E, Ali M, Wilson M, Menon V, Mehran R, Held C, Mahaffey KW, Lopes RD. Independence of clinical events committees: A consensus statement from clinical research organizations. Am Heart J. 2022; 248:120-129. doi: 10.1016/j.ahj.2022.03.005. Stevens G, Dolley S, Mogg R, Connor JT. A template for the authoring of statistical analysis plans. Contemp Clin Trials Commun. 2023; 34:101100. doi: 10.1016/j.conctc.2023.101100. Tong A, Oberbauer R, Bellini MI, Budde K, Caskey FJ et al. Patient-Reported Outcomes as Endpoints in Clinical Trials of Kidney Transplantation Interventions. Transpl Int. 2022; 35:10134. doi: 10.3389/ti.2022.10134. Vetter TR, Mascha EJ. Defining the Primary Outcomes and Justifying Secondary Outcomes of a Study: Usually, the Fewer, the Better. Anesth Analg. 2017; 125(2):678-681. doi: 10.1213/ANE.0000000000002224. Weintraub WS, Lüscher TF, Pocock S. The perils of surrogate endpoints. Eur Heart J. 2015; 36(33):2212-8. doi: 10.1093/eurheartj/ehv164.  #### Devices for the Military This past weekend I travelled to the Chicago-land area to attend my brother’s graduation from Northern Illinois University and commissioning into the US Army. He will be reporting to Fort Leonard Wood, Missouri for officer training as part of the Army Corps of Engineers. This has been a very proud and exciting time for all of us. Military personnel’s health challenges are very unique, and as such they require medical devices that are designed with their needs in mind. Take for example the BattleView Infrared Vascular Trans-illuminator. This device helps with the insertion of an IV in the dark by sending infrared energy to a patient. When the area is viewed with night vision goggles the veins appear to illuminate. This makes IV insertion in the dark much easier without compromising the operator’s position. Another interesting medical device designed specifically for the military is the CRoC (Combat Ready Clamp). The CRoC is the “only device approved for controlling hemorrhaging in every compressible, junctional emergency situation”. The device is designed to be rugged and amenable to different applications. These devices highlight the importance of understanding the end user and the environment. As a medical device community, I think we can be proud that so many devices have been created specifically for military applications. This innovation is one small way we can support those who serve our country and save lives. #### Don't Get Caught Off Guard: How to Meet the EU's 2024 MDR Deadlines To begin, a cautionary statement... The MDR transition timeline extension is not automatically applied to every legacy device! The timeline extension is conditional in nature, and there are a few key requirements that must be satisfied before manufacturers can benefit from this extension. It is important to note that the extension is designed to enable notified bodies (NB) to have sufficient time to assess applications, not to enable manufacturers to delay their submissions. To this end, the extension includes two critical deadlines for manufacturers:   26 May 2024, by which time manufacturers must have lodged an MDR application with their NB  26 September 2024, by which time the NB must have accepted this application. These interim deadlines are intended to prevent another crunch point of late applications as the new deadlines approach. What to do By getting the applications in now, NBs can plan effectively for their certification workload over the next few years, ensuring a smoother transition process. However, if you miss either of these deadlines, you will not be able to benefit from the timeline extensions; this may also impact your registrations in other countries if EU compliance was required for market access.  If you have not yet identified a notified body and submitted your application, or if your application has not yet been accepted, please note that acceptance of the MDR application is not a given: there are several strategic and tactical activities to be completed between now and 26 May 2024 to ensure a successful application.    If you are less confident and even slightly concerned about the conditional nature of the transition timeline and your company’s readiness, here are some critical items to consider:  Evaluate your product portfolio to determine if you are truly eligible for the MDR transition timeline extension. The EU Commission has published helpful guidance document here, to supplement the Q&A guidance on the extension published earlier this year. Ensure your NB application includes all information they require to provide a quote. Common pitfalls include gaps or inconsistencies in or relating to:The device description and intended purpose, including mode of action and elements which may require additional specialist consultation procedures (e.g. medicinal substances, animal tissues, Artificial Intelligence, etc.);Closely related to the above, device classification and justification;Critical subcontractors, their roles, and current state of QMS certification;Marketing or other claims which may impact the need for a clinical evaluation consultation procedure.Omissions or inaccuracies in the above can lead to a delay of many months in quoting and ultimately acceptance of your application for MDR certification.  Ensure your documented QMS is in compliance with the MDR requirements, considering EN ISO 13485:2016+A11:2021, prior to 26 May 2024, and that you have evidence of effective implementation. Ensure additional requirements for manufacturers and economic operators as described in Articles 10 – 15 are addressed and you have appropriate evidence of compliance. Ensure MDR post-market requirements (per Article 120) are fulfilled, and there is evidence of compliance beginning no later than 26 May 2021. These elements are not only essential to be able to continue to place your device on the market, but they will also form the necessary framework for any updates or remediation activities needed to achieve MDR certification. For next steps and more information, here are two fantastic options from our Knowledge Center: Read our guide: Mastering the Transition: 5 Essential Tips for EU MDR Compliance Watch BSI's Richard Holborow and RQM+'s Amie Smirthwaite discuss EU compliance in RQM+ Live! #69 #### Embracing Recalls By RQM+ Subject Matter Experts When managing recalls effectively, they don’t need to be feared – they can be embraced. Recalls get a bad reputation, especially when it comes to medical devices.  After all, these devices are meant to improve the lives of patients, and hearing that there’s something wrong with the device you are using that could lead to serious injury or death is the last thing that you want to hear.  But the truth is, despite our best efforts, recalls are sometimes necessary. However, when recalls are managed effectively - supported by a strong regulatory and quality strategy - they can be beneficial for both the patient and your company.  They provide opportunities for continuous improvement, transparency with customers and patients, and protect the brand/reputation.  Most importantly, quickly identifying and taking appropriate action on an issue shows a commitment to patient safety – which is ultimately the main priority. When managing recalls effectively, they don’t need to be feared – they can be embraced. FSCA, recall or advisory notice?   When a company takes action to reduce the risk of an issue with a medical device, there are several terms that may be used, such as recalls, Field Safety Corrective Actions (FSCAs), safety alerts, or advisory notices.  These terms will vary depending on regions.   However, the actions associated with these terms are the same.  A company may take action to correct, remove, replace, destroy, or modify a device within the field.  For this article, “recalls” will be used as a generic term to encompass all of these actions for all regions. Recalls are communicated to impacted consignees (customers, distributors, patients, etc.) through a letter.  In the United States, the letter is referred to as an “Urgent Medical Device Correction” (UMDC) letter.  In other regions, such as Europe, it is known as a “Field Safety Notice” (FSN). Different regions are also required to report to specific regulatory authorities within their jurisdictions.  Reporting timelines may vary, and there can be differences in what qualifies as a reportable recall.  However, even with regional differences, the overall requirements for a company taking these actions are the same. Best Practices for managing a recall When a recall is necessary, it is critical for the company to have a clear plan on how to implement the recall.  This includes everything from identification of the issue, communicating to stakeholders and impacted consignees, reporting to regulatory authorities, execution of required activities, and monitoring of the recall. Outlined below are the general steps and best practices for effectively managing a recall. 1. Identification of the issue   There are several sources for identifying an issue that may require a recall. Some examples include: Complaints / adverse event data  Internal reviews or testing data Audits  Manufacturing non-comformities Supplier notifications These issues can be triggered by many factors, such as device malfunctions, identification of health and safety risks, regulatory non-compliance, software failures, or labeling errors. This is why it is imperative to have strong quality systems and post-market surveillance in place, as well as a robust process for risk management. The sooner issues can be identified, the quicker a company can take the necessary actions.  When an issue is identified, there are often immediate actions that need to be taken prior to a decision on a recall.  For example, containment actions may need to be taken, such as quality or delivery holds, production holds, or quarantine. 2. Risk Assessment and Evaluation  Once an issue is identified, the scope and impact of the issue needs to be identified.  Risk Assessment: A risk assessment analyzes the potential risks the issue may have on patient safety or device performance. The assessment considers the risk for the general population, as well as the population(s) at greatest risk. It should also review the risk if removal of the device from the field is necessary to determine the availability of replacements or alternatives.  Keep in mind that if an issue is identified that is not currently included in the risk management file, the scope of the work surrounding the recall - and the necessary quality system remediation support - will likely be greater. This impacts not only the recall itself, but also the risk management process. Classification: Some regions may classify recalls into categories. These classifications are based on risk.  Classification systems are dependent on regions.  The table below shows an example of how recalls are classified in the US: US Classification Definition Class I Reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death. Class II Use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote. Class III Use of, or exposure to, a violative product is not likely to cause adverse health consequences. Corrective and Preventative Actions (CAPA): The root cause of the issue needs to be determined.  This is done through the CAPA process, consisting of the following: Root Cause Analysis Additional containment actions (e.g. quarantining additional devices identified during the root cause analysis) Immediate field corrections (e.g. issuing updated advice to users about detecting a fault situation and what to do when it is detected. This does not remove the issue but reduces the potential for harms to occur) Corrective Actions Secondary field corrections (e.g. the implementation of a corrective action on affected devices in the field such as the installation of a redesigned component) Preventative Actions (if applicable) When assessing the issue, keep in mind that there can be a fine line between a recall and modifying the device to enhance the functionality or performance.  The issue should be evaluated closely with necessary stakeholders, and all decisions should be thoroughly documented. If an enhancement to the device is deemed appropriate, ensure that a justification is included with the decision, and clearly explains why the action you are taking to enhance the device does not constitute a recall. 3. Creating a Team  Once a decision is made that a recall is necessary, a recall team will need to be put together. The team will work cross-functionally to implement the steps necessary to execute a recall.  Some key team members may include, but are not limited to: Corrections and Removals Specialist/Facilitator Risk Management Clinical and Medical Safety Legal Marketing Communications Regulatory affairs Engineering / Product Development Production Purchasing Logistics and distribution Servicing & repair Depending on the recall, the nature of the actions required, and the impact to safety, it may not be necessary to involve all of these stakeholders in every step.  Alternatively, more complex recalls may require a larger team of stakeholders from various other functions. Some things to keep in mind when deciding on your recall team: Try to limit the team to only the stakeholders that can provide productive input and expertise. With larger teams, you may experience delays in initiating your recall due to factors such as receiving feedback and input, waiting for approvals, and trying to coordinate meetings with everyone’s busy schedules.   However, it can also mean a more rounded review and strategy when the appropriate stakeholders are involved. Your team can grow, or shrink, as you begin to learn more about the specifics of the recall. 4. Planning and strategy If a decision is made that a recall is necessary, the recall team will need to develop a plan.  Key inputs when planning your recall include: Strategy: the strategy should take into account the circumstances of the recall that have been identified through the risk assessment.  This will determine the scope of the recall and whether a correction or removal is necessary.  The following factors should be included in your strategy: Identification of affected devices – Identify specific models, serial numbers, lots, or batches, and the impacted regions and consignees. Communication plans – Determine who needs to be informed (e.g. regulatory authorities, customers, distributors, patients, etc.) and the method of communication.  A recall letter should be distributed to all affected consignees.  Logistics – Develop a strategy for execution of the recall.  Will the device require a correction, or does it need to be removed from the field? How will  those actions be executed? Who will execute those actions? What questions should have answers in advance (e.g. who will pay for the field correction or replacement parts?)? Monitoring effectiveness of the recall – Effectiveness checks will need to be put in place to ensure that tracking of communication and the actions associated with the recall are effective. Your strategy should define the level and method of effectiveness checks required. Timing: Timing is crucial when it comes to planning your recall, especially in cases where there is a risk of serious injury or death.  Customers and patients need to be made aware of the issue in a timely manner, so that they can take appropriate actions on their end. There may be times when not all information is available, as further testing may be required to understand the issue but there may still be a need to take action to reduce the immediate risk before longer actions can be implemented.  In other cases, a resolution to fully address the issue may not be available right away (such as a software update).  In these situations, communication of the issue remains a top priority and should not be delayed.  Follow-up communications can be sent once further information is available. Recall Letter: All affected consignees must be notified of the recall. This is generally communicated through a letter.  As mentioned above, these letters are referred to differently among regions, but the intent remains the same.  At a minimum the letter should communicate the following: The product subject to the recall The issue that has been identified Any hazards/harms associated with the issue Actions that the customer, distributor, and/or patients need to take to mitigate the risk of the issue occurring Actions that your company is taking to fully resolve the issue The letter should be clear and to the point. Things to keep in mind when writing your letter: Ensure that recipients of the letter are provided with enough information to confidently identify the device subject to the recall. Describe the issue in a way for all audiences to understand.  Avoid details that are too technical. Don’t provide information that has not yet been confirmed by your company. If further testing or data is needed in order to better understand the issue, be transparent in the letter and state that further information will be provided once it is available. Ensure that the hazards/harms are clear enough so the recipient understands the risks of continuing to use the device. Do not downplay the risk associated with the issue. Be specific with instructions to the recipient on actions that they need to take. Be transparent in your strategy and the actions that your company will take to resolve the issue.  However, avoid committing to hard dates and actions that have not yet been established. Do not include marketing or promotional material. Consider including a listing of impacted serial numbers specific to each consignee, if possible Include instructions for consignees to acknowledge the letter. A form is typically included with the letter for consignees to fill out and return. Alternatives include the use of a QR code linking to an online form. 5. Execution Once a strategy is developed and communication is prepared, you can initiate and execute your recall.  Execution involves the following: Consignee notification: You company needs to inform all affected consignees of the recall.  This may include customers, distributors, and patients. Some things to keep in mind when notifying consignees: Different regions may have different requirements for communicating the letter to the affected consignees.  Sending the letter through the mail is most common.  However the letter is communicated, your company needs to ensure that communication is effectively tracked.  Each affected consignee should receive a copy of the letter. When sent through the mail, ensure that tracking information is available.  If other methods are used, such as email or telephone, ensure that all communication is documented. Your company will need to keep records of consignees that have been notified, as well as consignees that have and have not responded. Follow-up attempts should be made for those consignees who did not respond. Internal procedures should define how many attempts should be made to confirm receipt and what to do in the event of no response.  These are known as effectiveness checks for the communication of the recall.  Further details on effectiveness checks can be found below. Keep in mind that obtaining this information relies upon adequate traceability of distribution of your products, as well as distributors maintaining their records. The goal is to ensure your recall letters are sent to the intended audience that need to be aware of the recall.  Without systems in place for traceability, communication of the recall will be ineffective. Reporting: Regulatory authorities may need to be notified of the recall. As mentioned above, there are differences in reporting requirements depending on the region(s) affected by the recall.  Many regions have specific reporting forms or formats that should be submitted with your notification.  While some of the information may vary, these are the general details to include: Scope of the recall (affected models, batches, lots, etc.) Description of the issue The risks associated with the issue.  In many cases, providing a copy of the risk assessment is necessary. Details of the actions that your company is taking to resolve the issue (field correction, removal, etc.) Actions that customers should take to mitigate or prevent the risk of the issue Timelines for implementation Timelines for follow-up reports (e.g. progress of the recall) Reporting timelines will also vary across regions.  For example, FDA requires a manufacturer or importer to submit their report (known as an 806 report) to FDA within 10 working days of initiation of the recall (21 CFR 806.10).  FDA also requires monthly reports to monitor the progress of your recall.  Follow-up reports are also required for other regions, though the timing may vary. Although there are requirements for reporting, keep in mind that transparency with regulatory authorities is important. Early communication is beneficial, and when it comes to complex or serious recalls, having a discussion with them prior to initiation may be helpful. To make the most of your company’s time and the authority’s time, ensure that the appropriate stakeholders are involved in the discussion to speak to details of the issue that are pertinent to them.  For example, if there is a software issue, ensure that a software engineer is available to provide the technical information surrounding the issue. Monitoring: A company must ensure that their recall notification to consignees was effective, and that the actions to resolve the issue are being completed.  There are two key pieces to monitoring your recall: Effectiveness Checks: Effectiveness Checks verify that your recall communication was received by your consignees, and that they understood and followed the instructions provided in the recall letter.  A method for consignees to acknowledge notification of the recall should be provided should be provided with the letter (such as a form, QR code, etc.).  Tracking the progress of your recall: The specific actions required to resolve the issue identified in your recall will need to be monitored for completion.  The method for tracking this information will vary depending on a company’s capabilities. Some methods include: Inventory management systems Recall management software Return management systems/processes Documentation is critical in the execution phase.  Ensure that all consignee responses and correspondences are kept with the recall files, and that status reports are maintained and generated on a regular basis. Any additional decisions concerning the recall, such as a change in strategy, should also be documented.  These will all serve as inputs into status reports required for regulatory authorities, as well as request for closure of the recall. If the recall was initiated due to complaints or adverse events, records of additional complaints / adverse events should also be traceable to the ongoing recall. 6. Closure Once consignee notification has been confirmed according to the response rate identified in the strategy, and the actions associated with the recall have been completed, your company can request closure (or termination) of the recall with applicable regulatory authorities. A final report should be submitted to applicable regulatory authorities.  Although exact requirements may vary between regions, a final report typically includes: Scope of the recall The number of affected devices that have been corrected, removed, replaced destroyed, or modified within the field Corrective actions that have been taken Evidence of effectiveness Note: if the targeted effectiveness level that was defined in your strategy was not achieved, provide a justification as to why it was not met and why it is acceptable to close the recall Conclusion Recalls aren’t just about identifying an issue and going through the motions to fix it.  The priority should be on patient safety.  It’s easy to lose sight of that when we have so many other competing priorities in our day-to-day activities. But when we stop to remember the end goal, it allows us to focus on the impact that the recall has on patients relying on our devices.  But recalls can often be overwhelming and disruptive, often pulling us even further away from focusing on the end goal.  This is why understanding how to effectively manage a recall is so important.  When a robust recall management system and quality framework is in place, it allows for timeliness of communication, execution, and closure in a smooth and compliant manner. It also provides opportunities for continuous improvement, transparency with customers and patients, and protecting your company’s brand/reputation.  Ultimately, when we learn to embrace recalls we can get back to focusing on our commitment to patient safety. #### Engineering Plastics via Gel Permeation Chromatography Gel permeation chromatography (GPC) is a well-known method which is used for characterizing polymers according to their molecular weight distribution. The gel permeation chromatography analysis of engineering plastics at high temperatures needs specialized instruments and columns. The increased temperature is necessary across the entire experiment to inhibit re-crystallization and to keep the sample in solution. How does Gel Permeation Chromatography Work? Gel permeation chromatography instruments are made up of; a pump, to push the solvent through the instrument; an injection port, which introduces the test sample into the column; a column, to hold the stationary phase; one or more detectors, which detect the components as they exit the column; and software which controls the various elements of the instrument as well as calculating and displaying the results. Although polymers are chains, when they are analyzed by gel permeation chromatography they typically behave like tiny spheres, with the size of the sphere depending on the molecular weight. Polymers with a higher molecular weight coil up to form larger spheres. As components leave the gel permeation chromatography column, they are detected in numerous ways, and the elution behavior of the sample is shown in a graph, or chromatogram. The chromatogram displays the level of materials which have exited the column at any time, with the higher molecular weight, larger polymer coils eluting first, followed by successively lower molecular weight chains emerging later. How is Gel Permeation Chromatography Used in Engineering Plastics? Many recently developed types of engineering plastics display superior characteristics when put under high thermal or mechanical load. Such materials are designed to complement traditional materials like wood, metals or standard plastic. As the uses for these high-performance polymers increase, a need for methods which accurately and precisely characterize materials has arisen. Engineering plastics like ultra-high molecular weight polyolefins or polyphenylene sulfides have a higher mechanical strength and resistance to physical degradation. These properties are generally favorable, however when in the context of characterization of polymers, they can cause an issue. Analysis is challenging due to the crystalline nature of the materials, often needing elevated temperatures or less common solvents for a complete dissolution. Gel Permeation Chromatography Systems at RQM+ Lab Services RQM+ Lab Services is at the forefront of gel permeation chromatography, with extensive facilities and the ability to operate a broad range of gel permeation chromatography systems, including standardized gel permeation chromatography, tetra detection gel permeation chromatography and high temperature gel permeation chromatography. We deploy multiple detection methods which include ultraviolet, refractive index, multi-angle light scattering (MALS) and viscometry. At RQM+ Lab Services, we are also experts in the production of state-of-the-art polymeric media for gel permeation chromatography. Our gel permeation chromatography columns provide us the opportunity to apply multiple chemistries to the most complex method development projects. If you would like to find out more about our gel permeation chromatography solutions, contact us today. #### Enhancing Competitiveness in MedTech: Smart Strategies with Regulatory Intelligence What is regulatory intelligence? Ok, so what on earth are we talking about when we say regulatory intelligence? There are no formal definitions for regulatory intelligence in regulations or standards relating to medical devices or in vitro diagnostic devices. Without delving into the multitude of uses and dictionary definitions for ‘intelligence’, we can summarise them with some key phrases: Information gathering Understanding information Applying the learnings Regulatory intelligence is often talked about within the pharmaceutical industry and its usage frequency in the MedTech industry is steadily increasing. By amalgamating various definitions, we can understand regulatory intelligence (for the MedTech industry) to be: “…a systematic process of collecting, analysing, interpreting and disseminating information about regulatory requirements, policies, and guidelines that affect the development, manufacturing, distribution, and surveillance and regulation of medical devices and IVDs.” And “what is it for?”, I hear you ask. Well, the information gathered and insights gained can be used to inform decisions on business strategies (e.g. new products, new markets, new claims, favourable locations for study sites), to improve the overall effectiveness of regulatory submissions (e.g. avoiding common mistakes, reacting to new guidance, more accurate planning and budgeting), or to mitigate risks to regulatory compliance and/or business continuity, or to identify new or growing areas of technical expertise (e.g. where your organisation needs to bolster or improve competence in a technical subject such as cybersecurity or machine learning). Context is Critical The key steps in the regulatory intelligence process are illustrated in Figure 1. Figure 1. Illustration of the key elements of a regulatory intelligence process The act of gathering information includes collecting and analysing regulatory information from various sources, including regulatory agencies, industry associations, manufacturers, competitors, academics and scientific literature. That could be an endless task, so the context of your activities is critical to the effectiveness of your process, e.g. the nature of your business, your products and/or services, your competitors, the markets in which you operate, your customers, your future plans. If you fail to clearly identify the scope of your process, and tailor your methods, etc. accordingly, then you will find that you struggle to see the wood for the trees (or the forest for the trees, if you prefer) and your process seems inefficient and ineffective (Figure 2). Figure 2. The need to filter To make the information collection relevant for your organisation and objectives, you should understand and define the scope of your process: The types of information to be collected, The subjects/topics relevant to you, The sources of that information, The availability of that information, The frequency that the information is made available. The application of these constraints and filters can be visualised similar to the illustrations of the swiss cheese model, often used to show the effect of combining multiple layers of imperfect control measures (Figure 3). By restricting and filtering the information gathered, it makes the analysis and triaging of the information much more manageable. The information can then be assessed for relevance, significance and urgency. Figure 3. Adapted illustration of the swiss cheese model An ounce of action is worth a ton of theory You now know what is changing or what is incoming or what has happened. Do not just sit on the information gathered; if it is relevant, what is it to be done about it? Again, the context of your organisation is crucial. Does it affect regulatory compliance? Is it imminent? Which products/services are affected? Which markets are impacted? What is the scale of impact on products/services? What kind of work will you need to do in response? Then it simply becomes an action management activity: define your actions clearly; ensure that they are measurable and achievable; assign an action owner and a feasible completion date; ensure that the required resources are identified and made available. Depending on the size of organisation and the preferred decision-making processes, the need for action may be agreed quickly and then disseminated to the applicable personnel, or a proposal for action may be put to a panel of decision-makers to decide whether they agree with the proposal (and the assessment) before communicating the agreed actions to the applicable personnel. If products, regulated activities or quality management system processes are impacted then the action management could fall within your organisation’s corrective and preventive action process. This depends on whether a nonconformity has already occurred due to the event or could occur if action is not taken before the event. Some examples are provided below: Example 1, publication of ISO 14971:2019, provides a non-exhaustive illustration of a high-impact event that would need to be managed within the scope of the quality management system. In this example, the thorough analysis done at the outset, lays the groundwork for a detailed and prioritised quality plan. This attention to detail and planning goes a long way in demonstrating control within your quality management system. No regulatory authority or conformity assessment body will expect major updates like this to be implemented immediately across all affected products, but they do want to see that you understand what is needed, have a plan with resources in place to execute the changes, and have prioritised the workload proportionate to risk (Note: they may disagree with you on this front!). Leaving these updates until the last minute or until they are requested / demanded, is not prudent as it typically results in audit findings or delayed submissions, for which the timeline for completion moves away from your immediate control. Example 2, announcement of a proposed amendment to the US Quality System Regulations, shows a non-urgent low-impact event, that may turn into a high-impact situation later. This example highlights the benefits of active monitoring of the regulatory landscape even for non-urgent topics. Being aware of the proposal, the narrative around the proposal, the feedback from other stakeholders, etc. provides a good foundation to make preliminary judgements on what work will be required for implementation further down the line when the proposal becomes regulation. It enables informed decisions to be made when planning for resources and the timings of other activities. Being unaware of the proposal could leave you with a sudden, unplanned resource demand that negatively impacts the success on other business projects (e.g. submissions, site certifications). COLLECTISO 14971:2019 was published in December 2019 by ISO, quickly followed by EN ISO 14971:2019 and the national adoptions of those standards.TRIAGEConsider:What is the impact on the QMS?What is the impact on products already on the market?What is the impact on products currently in development and/or in the regulatory conformity assessment process?How critical is conformity to ISO 14971:2019 to regulatory compliance, competitive products and meeting customer expectations?Have the applicable regulators made any announcements about the new version? (e.g. has the EN version been harmonised for the EU? Have the FDA recognised this consensus standard?)Have the applicable regulators given any requirements or expectations for implementation?ANALYSEReview the 2019 version.Compare with ISO 14971:2009 and EN ISO 14971:2012.Identify any: new requirements; removed requirements; modified requirements, new/removed/modified informative guidance.What are the (high-level) differences between the requirements of the 2019 version and your risk management process and procedures?In general, what kind of updates will be required to risk management Files to bring them up to the level so that conformity with ISO 14971:2019 could be maintained. Do all existing risk management files conform to your current risk management procedure, or do they differ depending on age and product origins?DISSEMINATEShare with internal stakeholders; include them in the action-planning.ACTDocument a gap assessment of your risk management process and procedures against ISO 14971:2019, including examples from existing and current risk management files.Plan for and document the changes needed for the risk management process and procedures, and how those changes will be communicated to those responsible for creating and/or maintaining risk management files and all other personnel involved in the risk management process.Update your risk management process and procedures (this would typically be seen as a corrective action, i.e. procedure is no longer conforming to the standard to which it claims conformance).Develop and document a plan/protocol for how to upgrade/remediate the existing risk management files (i.e. a plan for how implement the updated procedure and correct the risk management files…a correction). Include the methodology for what to do if new risks or ineffective controls are identified. Include criteria for escalating issues to management.Include prioritisation of risk management files based on:product classification,regulatory compliance risk (e.g. time to next submission or audit),commercial importance of product,lifecycle management status (e.g. if design change is planned this would be more urgent to update than a product that is intended to remain static for a few years),state of the existing risk management file (compared with current process).Roll out training to identified personnel to ensure that the updated procedure and the correction plan can be implemented effectively.Implement the correction plan/protocol and update the individual risk management files accordingly. Example 2: Amendments to the US Quality System Regulation (QSR) COLLECTFDA publish final rule for amendments to the Quality System RegulationTRIAGEConsider the impact on existing products on the US market, planned submissions for the US, the sites responsible for those devices, scheduled audits, and likely FDA inspection dates.There is a two year time frame for implementation.ANALYSEWhat are the amendments?What are the differences between the old and the new?How do the amendments relate to the current QMS?What are the high-level differences between the current QMS and the requirements of this proposal?Which sites / product portfolios are affected by the amendment?How will the amendment impact on inspections methods, etc.?Are some sites or quality systems more at risk of non-compliance than others? E.g. they are not currently certified for ISO 13485:2016.DISSEMINATENotify all internal stakeholders, especially for those responsible for quality compliance, and include the topic in upcoming Management Reviews.ACTStart a gap assessment on the amended rule.Establish a quality plan on the back of the results from the gap assessment; identifying actions, priorities, action owners, due dates, required deliverables.Continue to monitor FDA communications for updates and further news.Monitor other sources of insight (e.g. blogs, webinars etc.) from industry experts for their insights into interpretations. Sounds a lot like Post Market Surveillance to me! Post market surveillance should look for data from both internal and external sources. Figure 4 highlights some of the areas to be considered for external data (Note: so does not include sales data, internal non-conformance or corrective action data). For a device manufacturer, there is probably a significant amount of overlap between the information gathered and analysed for regulatory intelligence purposes and for product-specific post market surveillance activities (Figure 5). The scope of the two processes may be the same or similar (because they are both based on your organisation’s context) and the process steps and tasks may be almost identical, but the objectives of the two processes differ. Post market surveillance is about monitoring the safety and performance of your device via proactive and reactive data collection methods, followed by analysis and evaluation of the collected data (or the ISO 13485:2016 definition if you prefer: “systematic process to collect and analyse experience gained from medical devices that have been placed on the market”). As described earlier in this piece, regulatory intelligence is unlikely to be product-focused (unless you only have one product in your portfolio), but it is intended to help inform business strategies and decisions. These decisions may be product-related, such as changes of direction for launch strategies or new ideas for lifecycle management of a product. Alternatively, it may relate to commercial activities, or operational decisions that may span all or multiple products, or may be independent of products completely. Figure 4. Simple illustration of the external sources of post market surveillance information Figure 5. A simplified overview of the relationship between regulatory intelligence and post market surveillance Does that mean that having a post market surveillance process negates the need for a regulatory intelligence process? No. As said above and shown in Figure 5, these two related processes have a lot of similarities but their respective objectives are different. That means that the same information can be reviewed but with two different mindsets. For post market surveillance the focus is simply on the product or product family: what does this mean for this product? For regulatory intelligence the focus is broader and is looking at all products and commercial activities; it is looking at the horizon to avoid compliance issues in the future; it is scanning data to seek out commercially advantageous regulatory strategies. But there is more to regulatory intelligence than just an alternative take on post market surveillance. Proactive regulatory intelligence as part of product development Up to now, we have focused on the reactive and proactive collection of information on a routine basis, but regulatory intelligence can also be used for a planned collection activity with a very specific focus. A good example of this is the research done to build a regulatory strategy that informs the design and development plan and the commercial launch strategy (see Example 3 below). Key elements to consider include: applicable regulations, product classifications, applicable reimbursement codes, suitable claims to target, claims to avoid, known safety issues and failure modes, applicable testing schemes, and applicable safety standards to apply. This research is also very similar to that performed to understand the generally acknowledged state of the art as part of a clinical evaluation or performance evaluation (as required per applicable regulations). Example 3: Building a regulatory strategy COLLECTCollect data on similar devices, competitor devices and predicate devices already on the market, including from:Registration databases such as the FDA’s and EUDAMED,Clearance/approval documentation from the FDA,Incident databases such as FDA’s MAUDE,IFU, marketing literature and manufacturer’s websites.Freedom Of Information (FOI) requests from the FDA,Other publicly available documents such as the Summary of Safety & Clinical Performance (SSCP) or Summary of Safety & Performance (SSP) for higher risk devices on the EU market.TRIAGEWhat information is applicable to the existing product plans?How does the information gathered change the existing plans or preconceptions?Is urgent course-correction required on the development project?ANALYSEAre there alternative routes to market?What are the criteria to be considered, or risk mitigations needed, in order to decide on which route is preferred?DISSEMINATEInform the relevant project team and responsible leadership of the findings and recommendations.ACTBuild your regulatory strategy incorporating all the available public knowledge.Make recommendations based on the acceptable risk and reward balance.Identify areas for further information collection and/or ongoing intelligence monitoring to refine and improve the regulatory strategy. Do we need a procedure for regulatory intelligence? Should it be part of our QMS? In short, yes and yes (for the routine intelligence gathering at least). Many medical device manufacturers have a quality management system conforming to, or at least based on, ISO 13485:2016. The objectives, purpose and methods for regulatory intelligence should address elements of maintaining quality management system effectiveness, quality management system planning, management review, product requirements and the general monitoring and measurement activities. Having a documented procedure as part of the quality management system provides assurance that specific tasks and deliverables have been identified, that roles and responsibilities have been assigned and that interfaces with other quality management system processes are understood (e.g. with the CAPA and change management processes). If there is no formal process or it is considered a business process rather than a quality system process, then there is a good chance that it will not be implemented or monitored as it would when under the focus of the quality management system. If that were to happen, key changes or events may be missed or seen too late, which negatively affects planning for quality system changes or product submission strategies. If the action requires identification and resourcing of specific competence from outside the organisation, ineffective intelligence gathering could mean that you are at the back of the queue when it comes to choosing talent. What does the regulatory intelligence process look like within RQM+? We don’t design, make or sell medical devices, our clients do. Our product is the services we provide to our clients. That is the lens through which we implement our regulatory intelligence process. Given that we have many different clients with varied product portfolios, that means our net is cast far and wide to try and ensure we don’t miss anything useful or beneficial. Whilst we have specific personnel who are responsible for the bulk of the intelligence gathering and analysis, it is also a collective effort with all personnel able to share information with the wider teams. We analyse the information with the following questions in mind: What is the potential impact for: Our clients? Our prospective clients? Our current projects? Our planned projects? Our processes, templates, and tools? Our future business strategies? Our marketing strategies? Once analysed and triaged, we share the information critical to our teams in proportionate time with an appropriate level of detail. This also usually includes archiving information in our internal Collective Knowledge Centre, a central repository for all things useful when it comes to MedTech, at least for regulatory affairs, clinical affairs and quality assurance. The aim here is to ensure that our teams have the relevant intelligence information and insights available at their fingertips, ensuring that they are not surprised if an existing client suddenly asks, “Have you seen that proposed amendment to the regulation? What do you think it means for us?”. It also enables our consultants to find guidance documents or standards by subjects or product areas. It is also appropriate to be transparent here; clearly, we use these intelligence insights to position ourselves advantageously for new clients, new projects, etc. as do all other successful service providers. Also, some of these insights are made publicly available for everyone via our RQM+ Live shows, our technical blogs, our other website content and our LinkedIn posts.  More RQM+ resources at your fingertips: View Webinar For those eager to deepen their understanding and enhance their strategic approach, RQM+ offers a wealth of educational resources designed to elevate your regulatory intelligence capabilities. From detailed guides to insightful webinars, our resources are tailored to empower your team with the knowledge and tools necessary to leverage regulatory intelligence effectively. Explore our offerings and join the community of MedTech professionals who are already benefiting from the competitive advantage that RQM+ educational resources provide. Embrace the power of regulatory intelligence with RQM+ and drive your organization towards greater innovation, compliance, and market leadership. Watch RQM+ Live! #76: MDCG 2023-7: New Clinical Evidence Pathways for Legacy and New Devices Watch RQM+ Live #75: Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers Follow #MedTechVoices on LinkedIn and get insights from our team as they analyze each of the opinions published by the Expert Panels as part of the Clinical Evaluation Consultation Process.  Follow RQM+ on LinkedIn for all of our updates! Nancy Morrison’s Keys to Thriving in Regulatory Affairs: Lessons Learned from a 30+ Year Career #### Enough Is Enough: Deciding When Your Safety Evaluation Is Complete For any MedTech company, the goal of developing products that are both effective and safe is at the heart of their mission. But as these companies build their products, they inevitably encounter testing challenges. Comprehensive testing, while crucial, often comes with a hefty price tag and developmental bottlenecks.  Given these constraints, it's no surprise that companies question their safety evaluation, leading them to ask: "When is enough, truly enough?" In this article, we'll provide an answer. But first, let’s explore how regulatory concerns ensure that any answer we do arrive at is likely to change sooner rather than later. The Regulatory Landscape is Constantly Shifting — Just Like Your Safety Requirements Over the last few years, dramatic changes to MedTech standards and regulatory requirements have placed new demands on safety evaluations.  In the EU, for instance, MDR now mandates that qualified toxicologists lead toxicological risk assessments — previously engineers could take on this role. Recent standards updates, such as ISO 21726:2019, ISO 10993-18:2020, and ISO 10993-17:2023 further underscore these rapid changes and raise the bar of safety and efficacy.  This evolution has introduced advanced sensitivity levels in testing, including novel considerations that didn’t exist a decade ago. As the landscape shifts, MedTech companies need to grapple with both written and unwritten, ever-changing expectations. In this environment, agility is essential for companies to remain compliant and competitive.  Keeping pace with change is, therefore, key to aligning your product with current and future demands — and to knowing whether your safety evaluation is complete.  Is Biocompatibility Testing or Chemical Characterization Good Enough?  To improve efficiency, many MedTech companies wonder if biocompatibility testing or chemical characterization is sufficient to prove the safety of their products. Of course, every scenario is unique. But trying to get away with performing one test over another can leave areas of weakness in your safety evaluations. Different testing methods are often relevant to different product development stages. For instance, material characterization — a process that’s distinct from chemical characterization — is prioritized during early research and development. At this point, testing focuses on functional concerns and finding the right material.  As development progresses and a prototype is created, traditional biocompatibility is needed to assess biological reactions caused by extracted materials. As the product nears its final design and before it goes to market, the focus shifts to chemical characterization. This method is key to meticulously identifying and quantifying the chemicals that a device may release, while assessing their associated toxicological risks. By revealing a device's detailed chemical profile, chemical characterization directs manufacturers to specific areas that necessitate further biocompatibility evaluation. To Test is to Iterate Just as a clinical investigation report doesn't equal a complete clinical evaluation report, multiple biological compatibility tests don't automatically result in a comprehensive biological safety report. These evaluations feed into broader risk assessments, leading to subsequent tests, and culminating in an overarching biological evaluation. Ultimately, MedTech safety isn't about cherry-picking evaluations but cohesively blending them. This rigorous approach helps create bullet-proof safety evaluation reports — leading to time and cost savings as the product enjoys fewer regulatory hurdles and a faster time-to-market.  A Checklist for Complete and Accurate Safety Evaluations It can be difficult to determine when your safety evaluation is ready for regulatory submission. Here are some points to consider: Regulatory Alignment: Is your testing in sync with the latest regulations and standards? Have you accounted for region-specific testing requirements? Holistic Evaluation: Does your safety evaluation strategy incorporate all necessary testing, e.g. both biocompatibility testing and chemical characterization? Have you sidelined any testing phases or evaluations, thinking they might be redundant? Expert Review: Do you have the right experts performing tests and evaluating the product? Have you consulted industry experts to validate your safety evaluation strategy? Product Lifecycle Consideration: Have you tailored your testing approaches according to the product development stages? Are you capturing the right data at each stage of product development? Continuous Regulatory Monitoring: Are you updated with the latest changes in standards and regulations? Have you set up mechanisms to keep pace with evolving regulatory expectations, both written and unwritten? Future-proofing Your Processes Are your safety evaluations robust enough to withstand anticipated regulatory shifts in the near future? Is your approach proactive, ensuring your product remains relevant and compliant in the years to come? How RQM+ Can Help You Submit Complete Safety Evaluations The MedTech regulatory ecosystem is anything but static. Ensuring products conform to current standards isn't just about meeting present-day requisites; it's about foreseeing shifts and being prepared for the future.  This is where RQM+ can help. As a full-service CRO, RQM+ provides a seamless pathway to accelerate the MedTech product journey from concept to commercialization. Our comprehensive testing, analysis, and validation services to support regulatory compliance while minimizing delays in product development. This, in turn, minimizes risk to both end users and your company, thereby protecting your brand and reputation for the long haul. From designing a comprehensive safety evaluation strategy and performing lab tests to preparing and submitting the biological evaluation report, our expert Lab Services team can help you develop complete safety evaluations.  Don’t let regulatory challenges hold you back. Contact our team now to find out how we can support your safety evaluation process.  Contact Us #### Ensuring Compliance with FDA’s Final Rule for Laboratory Developed Tests (LDTs) The FDA’s final rule regulating Laboratory Developed Tests (LDTs) marks a pivotal shift in compliance requirements for clinical laboratories. Adapting to these regulations requires a strategic approach that aligns with FDA expectations and existing CLIA requirements. For many laboratories, navigating this transition poses challenges due to limited experience with FDA processes. RQM+ offers a systematic, flexible approach designed to guide laboratories through this regulatory shift, ensuring compliance without disrupting operations. This technical brief outlines our structured methodology for guiding laboratories through the transition from CLIA-based compliance to full FDA compliance, incorporating comprehensive gap assessments, risk mitigation strategies, and long-term regulatory planning. Readers will gain valuable insights that can inform their compliance strategies, making this brief a worthwhile resource regardless of the specific approach. Background The FDA’s decision to regulate LDTs as medical devices introduces several key challenges: Developing compliance strategies for full and partial enforcement discretion requirements within the final rule Meeting Medical Device Reporting (MDR) requirements Transitioning from CLIA to FDA Quality System Regulation (QSR) compliance Implementing design control and risk management processes Understanding FDA expectations for IVD validation versus CLIA requirements for LDTs Adapting to new premarket submission obligations To remain competitive and maintain market access, laboratories must proactively align their Quality Management Systems (QMS) and product classifications with the FDA's final rule. Who RQM+ Supports RQM+ offers strategic consulting services to a diverse range of organizations impacted by the FDA’s final rule on LDTs. Our services are tailored to each client’s unique needs and existing framework rather than providing a one-size-fits-all solution. Clinical Laboratories: High-complexity labs developing proprietary LDTs that must transition from CLIA to FDA oversight. Hospitals & Academic Medical Centers: In-house diagnostic labs requiring compliance with FDA premarket review and QMS requirements. Specialty & Genetic Testing Companies: Providers of high-risk or novel diagnostic tests who need risk classification and regulatory submission strategies. IVD Manufacturers & Companion Diagnostics Developers: Companies collaborating with laboratories to ensure compliance with FDA regulations. Biotech & Pharmaceutical Companies: Firms developing biomarker-driven LDTs now subject to new regulatory scrutiny. Investors & Private Equity Firms: Entities assessing regulatory impacts on LDT-focused portfolio companies. Case Study:LDT Assessment & Remediation Project A leading CLIA-certified specialty testing laboratory partnered with RQM+ to transition to FDA compliance under the final rule. Challenge The laboratory faced a significant regulatory shift, requiring an evaluation of its quality system, product classifications, and regulatory readiness. Despite a strong compliance history under CLIA, the lab lacked experience with FDA expectations and processes. Given its large test menu, including FDA-cleared tests, FDA-modified tests, and in-house developed LDTs, it needed to maintain CLIA-compliant processes with minimal disruption while adapting to new FDA requirements. Solution RQM+ conducted a comprehensive gap assessment to identify areas where the laboratory’s existing QMS and product development processes did not align with FDA expectation. Outcomes Identified compliance gaps for each stage of the final rule’s phased implementation Developed a strategic transition plan to meet FDA requirements Created a roadmap for remediation and premarket submission strategies for high-risk LDTs Provided ongoing guidance to ensure continued alignment with FDA compliance deadlines Detailed Summary Of Key Activities Regulatory Strategy and Change Impact Assessment Conducted a detailed review of the test menu, including the regulatory status of each test and applicability of full or partial enforcement discretion policies. Evaluated the potential use of the “grandfathering” partial exemption for tests marketed before May 6, 2024, assessing the risks and benefits based on prior and planned modifications. Complaint Handling and Medical Device Reporting (MDR) Gap Assessment Reviewed the lab’s existing complaint handling procedure and electronic tracking system to identify gaps in meeting FDA complaint record requirements. Clarified the distinction between FDA-defined “complaints” and those governed by CLIA or business needs. Analyzed one year of historical complaints to determine which would be FDA-reportable. Developed a strategy for updating complaint procedures and electronic tracking systems for Stage 1 compliance. Test Validation Review Assessed validation procedures, ensuring alignment with FDA’s emphasis on individual test performance validation rather than CLIA’s process-driven approach. Evaluated a subset of validations across all LDT technologies, identifying gaps and providing remediation strategies aligned with the staged implementation of the final rule. Provided guidance on efficient use of FDA pre-submission requests. Quality Management System (QMS) Gap Analysis Conducted a comparative analysis of the lab’s CLIA-compliant QMS against FDA Quality System Regulation (21 CFR 820) and the FDA’s Quality Management System Regulation (QMSR), which aligns with ISO 13485:2016. Established a remediation roadmap for achieving Stage 3 compliance by May 6, 2027. Key Compliance Milestones & Deadlines May 6, 2025: MDR, Complaint Handling, Correction & Removal Reporting. May 6, 2026: Establishment Registration, Device Listing, Labeling, IDE. May 6, 2027: Full QSR implementation, including design controls, CAPA, and supplier management. November 6, 2027: Premarket review for high-risk LDTs (IVDs). May 6, 2028: Premarket review for moderate and low-risk LDTs. Why Partner with RQM+ RQM+ is a trusted regulatory partner with deep expertise in IVDs, LDTs, and FDA compliance. Our tailored, strategic support ensures laboratories meet regulatory deadlines while maintaining operational efficiency. Take Action Now: Contact RQM+ today to discuss how we can support your LDT compliance journey. About the Author Margot Borgel, Ph.D. is an expert in the technical and regulatory requirements of in vitro diagnostics (IVDs) and laboratory developed tests (LDTs) with over 12 years of experience in both the US and EU markets. She was recently appointed to the CLSI Strategic Laboratory-Developed Test (LDT) Final Rule Advisory Group, which was established to support CLSI’s response to LDT regulation. At RQM+. She helps clients meet regulatory requirements for IVDs and LDTs through strategic regulatory support and guidance throughout the entire product lifecycle. She also performs regulatory intelligence activities at RQM+ to ensure compliance to the ever-changing IVD regulatory landscape. Margot holds a BSc and Ph.D. in Chemistry and has IVD experience within the industry as well as with an EU notified body. A strategic thinker and collaborator, she has an extensive scientific background in assay development, IVD manufacturing, process improvement, regulatory requirements, and quality management systems. She is a subject matter expert for performance evaluation and clinical requirements, international standards, and guidance documents for IVDs and LDTs. Margot is passionate about supporting companies looking for market access of their innovative test systems and IVDs and takes on every project as if family was on the other side of the diagnostic. Feel free to connect with Margot on LinkedIn here. #### Europe, the EU, and the EU Single Market: geopolitical implications for MedTech By Chris A. Parr - Principal, CRO As a follow up to “Recent developments in EU Horizontal Legislation” and “Medical Devices, IVDs and Other EU Laws” we will now demystify Europe, the EU and the EU single market so that manufacturers have an improved awareness of European countries and territories where they can achieve market access with the CE mark. Europe and The European Union (EU)   To set the scene, it is necessary to first define the terms “Europe” and the “European Union” (EU). Europe is one of the seven continents of the world and is a broad geographical term that includes all countries located on the European continent. Whereas the EU (see graphic below) is a political and economic union of 27 European countries1 that have agreed to work together more closely in areas like trade, law, security, and environmental policy. Not all European countries are members of the EU; 22 European countries are not members of the EU2. The EU Single Market is one of the core foundations of the European Union. It allows for the free movement of four key things across all EU member states. The CE mark enables the free movement of medical devices and IVDs in the EU Single Market. Goods – Products can be traded across borders without tariffs or customs checks. Services – Businesses can offer services in any EU country. People – Citizens can live, work, study, or retire in any EU country. Capital – Money can move freely for investment, banking, or business. European Free Trade Area (EFTA) and European Economic Area (EEA)  Now we have defined the EU and the EU Single Market, we will move on and cover the European Free Trade Association (EFTA) and the European Economic Area (EEA). EFTA is a regional trade organization and free trade area made up of four European countries. It was founded as an alternative to the then-European Economic Community (EEC), which later became the EU. EFTA promotes free trade and economic cooperation among its members and with other countries worldwide. Iceland Liechtenstein Norway Switzerland The European Economic Area (EEA) is a region that brings together the 27 EU member states and three of the four EFTA countries (Iceland, Liechtenstein, and Norway) into a single internal market. The CE mark enables the free movement of medical devices and IVDs in the EEA. EU Outermost Regions The EU Outermost Regions (ORs) are parts of the EU member states France, Portugal, and Spain that are geographically distant from mainland Europe but are fully part of the European Union (see details and map below). The name comes from Article 349 of the Treaty on the Functioning of the European Union (TFEU), which acknowledges that these regions: Are located far from continental Europe (often in the Caribbean, Indian Ocean, or Atlantic). Face permanent constraints such as:RemotenessInsularitySmall sizeDifficult topography and climate Map of European Outermost Regions3 These regions are subject to EU law and benefit from special support due to their unique challenges, such as remoteness, insularity, and economic dependence. This means that medical devices and IVDs marketed in the Outermost Regions must have a valid CE mark, just like in mainland France, Spain, or Portugal. Non-EU Countries with Customs Union Agreements Turkey Turkey is not part of the EU or EEA, instead it is part of a Customs Union with the EU that includes medical devices and IVDs. This means that medical devices and IVDs legally placed on the EU single market can also circulate in Turkey without additional customs duties or technical barriers, provided they comply with EU regulations. Devices must bear the CE mark to demonstrate conformity. Andorra Andorra, Monaco, and San Marino can be collectively described as European microstates. They are independent from the European Union (EU), but they each have special relationships with it. Andorra is not an EU or EEA member but has a customs agreement with the EU. Andorra does not have its own medical device or IVD regulatory framework. It relies on EU regulations, meaning CE marking is required for medical devices and IVDs placed on the Andorran market. Devices must comply with MDR/IVDR if they are to be imported or distributed in Andorra. Monaco Monaco is not an EU or EEA member, but it is in a customs union with France. As a result, French and EU regulations apply, including those for medical devices and IVDs. CE marking is required for medical devices placed on the market in Monaco, as they must comply with MDR/IVDR through French oversight. San Marino San Marino is not an EU or EEA member, but it has close ties with Italy and a customs union with the EU. CE marking is required for medical devices and IVDs placed on the market in San Marino, as they must comply with MDR/IVDR through Italian oversight. Switzerland Switzerland had a Mutual Recognition Agreement (MRA) with the EU covering medical devices and IVDs. However, this agreement ceased to apply fully after the EU Medical Device Regulation (MDR) came into force in May 2021, due to the lack of an updated institutional framework agreement between the EU and Switzerland. Switzerland is not a member of the EU or EEA and now requires Swiss-specific regulatory compliance (MedDO4). Switzerland unilaterally recognizes CE-marked medical devices and IVDs that comply with MDR/IVDR. United Kingdom The United Kingdom of Great Britain and Northern Ireland officially left the European Union on January 31, 2020. Great Britain (England, Scotland Wales) is no longer an EU member and does not have a customs union agreement with the EU. In GB, manufacturers can use the UKCA mark or the CE mark which is recognised until 30 June 2030 at the latest5,6. In contrast, Northern Ireland remains in regulatory alignment with EU rules by virtue of the Windsor Framework Agreement. This means that it effectively remains part of the EU Single Market for goods only. Therefore, the CE mark is required for medical devices and IVDs placed on the NI market. Summary Medical device manufacturers must understand the distinctions between Europe, the EU, the EEA, EFTA, and the EU Outermost Regions because these geopolitical and regulatory groupings determine market access, regulatory compliance, and product certification requirements. In the EU and the EEA, medical devices and IVDs must comply with the MDR (EU) 2017/745 or IVDR (EU) 2017/746. This includes Iceland, Liechtenstein, and Norway that have adopted EU medical device and IVD regulations through the EEA Agreement. It also includes the EU Outermost Regions that are part of EU member states but located outside Europe. Compliance with the MDR/IVDR is also required in countries with customs union agreements with the EU and in Northern Ireland due to its unique geopolitical situation. Lastly, compliance with the MDR/IVDR is an option for Great Britain and Switzerland who continue to recognise the CE mark. Related next steps If you’re having difficulty navigating the EU regulatory landscape and struggling to comply with horizontal EU regulations, our experts specialise in helping manufacturers develop comprehensive regulatory strategies designed to ensure that medical devices and IVDs comply with all applicable EU legislation. Contact us to discuss how we can support your efforts and stay tuned for more updates related to the European Medical Device landscape in our upcoming blog posts. For further reading - Braving the Tariff Storm: Strategies for MedTech Companies https://european-union.europa.eu/principles-countries-history/eu-countries_en#header_countries_list https://www.worldatlas.com/geography/european-countries-that-are-not-members-of-the-european-union.html https://ec.europa.eu/regional_policy/policy/themes/outermost-regions_en https://www.fedlex.admin.ch/eli/cc/2020/552/en https://www.gov.uk/government/publications/implementation-of-the-future-regulation-of-medical-devices/implementation-of-the-future-regulations https://www.gov.uk/government/publications/implementation-of-the-future-regulation-of-medical-devices/statement-of-policy-intent-international-recognition-of-medical-devices #### Exploring Clinical Trials Services for Alzheimer’s Diagnostics and Clinical Deployment Alzheimer’s disease presents one of today’s most urgent and complex healthcare challenges. Affecting millions worldwide—with numbers steadily rising—there is a critical need for early, accurate, and accessible diagnostics. Blood-based biomarkers, advanced imaging modalities, and digital tools are reshaping the landscape of Alzheimer’s detection. Yet transforming promising research into a clinical reality hinges on well-executed clinical trials.  For MedTech leaders and clinical operations professionals, engaging expert trial partners is essential to navigate the regulatory, operational, and scientific demands of these high-stakes studies. This article explores the intricacies of Alzheimer’s diagnostic trials and how specialized clinical trial services, such as those offered by RQM+, can streamline progress from lab to clinic. The Distinctive Requirements of Alzheimer’s Diagnostic Trials Unlike therapeutic trials, diagnostics must validate both analytical accuracy and clinical relevance. For Alzheimer’s, this often entails: Confirming biomarker reliability in asymptomatic or early-stage populations Linking diagnostic outcomes to clinical decision-making Demonstrating improved patient management pathways These trials must also address unique barriers: Early-stage patient identification: Many patients remain undiagnosed until later stages. Cognitive assessment sensitivity: Standard tools may not detect early cognitive decline effectively. Ethical complexity: Consent and communication must account for cognitive impairment. Global regulatory navigation: Especially with evolving IVD frameworks like FDA guidelines and the EU IVDR. Recruitment and Retention: Tackling the Enrollment Challenge Recruiting for Alzheimer’s trials requires locating individuals at early or preclinical stages—often before symptoms emerge. Fortunately, newer, less invasive tools such as plasma amyloid and tau assays are making broad pre-screening feasible. Enhancing recruitment and retention involves: Building relationships with memory clinics and PCP networks for patient referrals Leveraging digital registries and decentralized trial platforms to reach broader populations Offering caregiver and logistical support to maintain engagement across long trial durations Aligning Trial Design with Regulatory and Clinical Utility Designing diagnostic trials that meet both regulatory standards and clinical expectations is a balancing act. Success depends on integrating scientific rigor with real-world relevance. Design priorities include: Use of validated surrogate and composite endpoints Inclusion of multi-modal biomarkers (fluid and imaging) Compliance with IVD regulatory frameworks (FDA, IVDR) Embedding health economics and outcomes research (HEOR) to inform payer decisions Bridging the Gap: From Regulatory Approval to Clinical Deployment Even after market authorization, challenges remain. Physicians must adopt the test, systems must incorporate it into workflows, and payers must support its use. Key factors for successful clinical integration include: Post-market real-world evidence (RWE) generation to demonstrate ongoing utility Provider training and support to increase confidence in test interpretation Strategic engagement with payers to secure favorable reimbursement pathways How RQM+ Supports Alzheimer’s Diagnostic Trials RQM+ delivers full-spectrum clinical trial support, tailored to the distinct needs of MedTech and diagnostic developers. For Alzheimer’s diagnostics, their integrated capabilities include: Regulatory strategy development and pre-submission guidance Protocol design with neurodegenerative focus Specialized site networks for targeted patient recruitment Integrated biomarker analysis with partners like Jordi Labs Seamless data management, monitoring, and clinical operations Rigorous safety oversight processes  By aligning scientific, operational, and regulatory functions, RQM+ enables faster approvals, smoother clinical deployment, and ultimately, greater patient impact. FAQs Why are Alzheimer’s diagnostic trials more complex than other clinical trials?They must validate accuracy in early-stage populations, link diagnosis to clinical outcomes, and meet evolving regulatory standards specific to diagnostics and cognitive impairment. What biomarkers are being used in Alzheimer’s diagnostics?Emerging blood-based biomarkers like amyloid-beta and phosphorylated tau, along with imaging (e.g., PET scans), are leading the way in early detection. How does RQM+ ensure successful trial outcomes for diagnostic sponsors?Their integrated model combines regulatory insight, operational execution, and scientific expertise, tailored to the specific needs of neurological and diagnostic trials. Looking for Clinical Trial Services? Transforming breakthrough Alzheimer’s diagnostics into tools used in everyday care requires more than innovation—it demands strategic execution. Clinical trials are a pivotal step, and working with expert partners like RQM+ helps sponsors navigate the path with speed and confidence. For diagnostic developers in the Alzheimer’s space, investing in specialized clinical trial services is not only strategic—it’s vital. The sooner these tools reach clinicians, the more lives we can improve. #### Exploring the Importance of Polymer Analysis Polymers are ubiquitous materials used in construction, engineering, and countless commercial products. These applications can be as varied as the polymeric materials used in medical devices, pharmaceuticals, food and beverage packaging, and personal care cosmetics. They are made from repeating chains of bonded molecules that are typically organic but, in some cases, may even be inorganic in nature. Natural rubber is a polymer consisting of the simple hydrocarbon isoprene, while polyethylene (PE) is a synthetic plastic manufactured from ethylene monomers. A typical polyethylene may consist of up to 200,000 monomers, the composition, and concentration of which can have a significant impact on the qualities of the end-product. Polymer Analysis and Polymerization Polymerization is the process that causes small molecule monomers to covalently bind with one another and form tough interlinking polymer chains.  The polymer chain can be formed using a range of chemical species by heating or pressurizing samples in the presence of catalyzing agents. An assortment of engineering techniques is used to manufacture polymers with varying molecular weights and chemical-mechanical properties. For example, some epoxy resins are made through copolymerization with an amine, a process in which the polymer reacts with a hardener to form the final product. The physical properties and the applicability of a given polymer product fundamentally depend upon the composition and stability of monomers, additives, and copolymers used in the polymerization process. Analysis of the raw materials routinely precedes polymerization for quality control procedures. Continuing with the example of copolymerization, polymer analysis may reveal the materials’ deformation properties, which can then be modified through additional curing or hardening stages during manufacture. Polymer Analysis and Deformulation Polymer analysis is also a routine part of product deformulation and failure analysis. Mass spectrometry and gel permeation chromatography are widely used methods for assessing the composition, and both the primary and residual concentration of monomers in an end-product. These methods can also be used to measure the molecular weights of polymers of up to millions of molecular weight. The importance of polymer analysis cannot be understated. It is used for both research and development, quality control, and failure analysis in an enormous range of industrial and commercial applications. Products from biodegradable plastic bags to carbon-reinforced-polymer car parts depend on polymer analysis to ensure that the material can withstand application-specific strains and conditions. Polymer Analysis with RQM+ Lab Services Polymer analysis is at the heart of what we do at RQM+ Lab Services. We have been successfully analyzing polymeric products since 1980, having already assessed every major class of commercially available polymers including: Polyolefins (PE, PP etc.) Styrenics (PS, ABS, SAN etc.) Biodegradable Polymers Butadiene-based, natural and synthetic rubbers Polysiloxanes Thermoset resins (melamine, phenol formaldehyde, epoxy etc.) Polyesters (PET, PBT, PCL, PGA, PLA etc.) Polyethers (PEG, PPG etc.) Polycarbonates Nylons Vinyl polymers (PVC, PVA, EVOH) Polysaccharides and Cellulosics Polyurethanes and ureas Methacrylates and acrylates Cationic, anionic and zwitterionic polymers Fluoropolymers If you would like any more information about performing polymer analysis with RQM+ Lab Services, please do not hesitate to contact us. Learn more about polymer analysis - The Basics of Polymer Analysis: Techniques & Solutions Characterizing Polymers for Novel Sustainability Initiatives #### FDA Friday: Reclassification In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  The longer you know someone, the more you learn about them. Well, the same goes for medical devices! As knowledge about a medical device increases, we inevitably have a better understanding on its benefits and risks. As our understanding of a device evolves over time, it is possible that the classification of the device might need a little update. There are two different ways for a medical device to be reclassified at FDA, both of which we review below. First, there is a way for a medical device to be reclassified as described in the Food, Drug and Cosmetic Act (the Act). Under Section 513(e) of the Act, FDA may reclassify a device based on new information, whether it is discovered on their own, or in response to a petition from an interested person. In this case, “new information” is defined as publicly available, valid scientific evidence. If FDA or a petitioner proposes that a device be reclassified to a lower class (say from the higher risk Class III to a moderate risk Class II), sufficient and valid scientific evidence must be provided in order to support the determination. In July of 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was created, which changed the reclassification process to an administrative order process instead of rulemaking. According to FDA’s website that discusses reclassification, in order to reclassify a device under this section of the FD&C Act, FDA must do the following before making the reclassification final: §  Publish a proposed order in the Federal Register that includes proposed reclassification and summary of the scientific evidence supporting the reclassification §  Have a panel meeting for the device classification before or after the proposed order has been published §  Take comments from the public docket into account There are also additional rules and guidelines that apply depending on the original class level, and the new class level for a device. For example, for devices being reclassified from Class II to Class III, the scientific evidence must indicate that the general and special controls are insufficient to provide reasonable assurance of safety and effectiveness. Conversely, if a device is being reclassified from Class III to Class II, the scientific evidence must show the opposite; that the general and special controls are sufficient to provide reasonable safety and effectiveness. Lastly, if a device is being reclassified to Class I from either Class III or Class II, the scientific evidence must show that the general controls alone are sufficient to provide reasonable assurance of safety and effectiveness. The other route for devices reclassification is described in Section 513(f)(3) of the FD&C Act. This originates from the understanding that any device not available before the Medical Device Amendments in 1976 was automatically classified as Class III. This classification was determined regardless of any risk the device posed, and without undergoing any FDA rulemaking processes. These medical devices are more commonly known as postamendment devices. Unlike the process above, these devices may only be considered for reclassification if the initiative comes from FDA or a petition from a manufacturer or importer. Similar to the 513(e) process discussed in the previous paragraph, reclassification of a device can only be made when sufficient regulatory controls can provide reasonable assurance of safety and effectiveness. A device reclassification panel may also be called, should FDA receive a petition requesting reclassification. After all information has been considered, FDA will determine whether the reclassification petition is approved or denied. Following approval, the order describes both the reason for reclassification, as well as any of the device’s risks to patient health. By the way, if you’re wondering where the whole de novo process fit here, you should check our previous blogs. Keep in mind, a de novo request (per 513(f)(2) of the FD&C Act) is a file where a submitter can request a new classification altogether. Therefore, we don’t really consider it a ‘reclassification’ per the definition of our subject in this blog. To see a full list of medical devices that have been reclassified since 2013, visit this link. If you’re wondering why the list only goes back five years, it’s because it wasn’t until FDASIA was enforced in 2012 that FDA was required to annually post the devices reclassified in the year prior. Additional Reading: Overview of Medical Device Classification and Reclassification Classify your Medical Device #### FDA Inspections Database The Food and Drug Administration (FDA) recently released its new data set for the Inspections Database. 1-2 The Inspections Database makes available the most recent inspection (up to two years of inspections) of a company. The final inspection classification for clinical trial investigators and Institutional Review Boards (IRB), as well as manufacturing, processing, and packing facilities’ final inspection classifications are disclosed.3 The inspection classification of facilities that hold an FDA-regulated and currently marketed product is also listed on the FDA inspection database. Currently, there are three types of inspection classification: 4 No Action Indicated (NAI) - This type of inspection classification is given when “no objectionable conditions or practices were found during the inspection or the significance of the documented objectionable conditions found does not justify further actions.”4 Voluntary Action Indicated (VAI) - “Occurs when objectionable conditions or practices were found that do not meet the threshold of regulatory significance. Inspections classified with the VAI violations are typically more technical violations of the [Food Drug and Cosmetics Act]”4 Official Action Indicated (OAI) - This type of inspection classification is given when “significant objectionable conditions or practices were found and regulatory action is warranted to address the establishment’s lack of compliance with statute(s) or regulation(s)”.4 To view the FDA Inspection Classification Database Search, CLICK HERE.2 For more information on Search Form Fields, within the Inspection Classification Database Search, please visit FDA’s website http://www.accessdata.fda.gov/scripts/inspsearch/searchfields.cfm. 5 If you have any questions pertaining to the Inspections Database, please send an e-mail to FDAInspectionsClassficiations@fda.hhs.gov.3 To make a request for official counts of inspections, please send an e-mail to the FDA’s Office of Media Affairs at fdaoma@fda.hhs.gov., with the subject heading “Inspection Court”.3 Do you have any questions or comments about this blog? Feel free to leave your feedback! -RSpelich ^_^ References FDA. Inspection Classification Definitions. Last updated 05/24/11. Accessed 24 June 2013. Available at: http://www.fda.gov/ICECI/EnforcementActions/ucm223231.htm. FDA. Inspection Classification Database Search. Data reported as of June 2013. Accessed 26 June 2013. Available at: http://www.accessdata.fda.gov/scripts/inspsearch/. FDA. Inspections, Compliance, Enforcement, and Criminal Investigations. Last updated 07 June 2013. Accessed 24 June 2013. Available at: http://www.fda.gov/ICECI/EnforcementActions/ucm222557.htm. FDA. Inspections. Accessed 24 June 2013. Available at: http://www.fda.gov/downloads/AboutFDA/Transparency/PublicDisclosure/GlossaryofAcronymsandAbbreviations/UCM212061.pdf FDA. More Information on Search Form Fields: Inspection Classification Database Search. Accessed 25 June 2013. Available at: http://www.accessdata.fda.gov/scripts/inspsearch/ #### FDA Proposed Rule: Impact on Wound Care Devices The FDA's recently proposed rule on wound care products has sent ripples through MedTech. This rule, if finalized, could significantly impact the classification, labeling, and testing requirements for a wide range of wound care devices. FDA is proposing to classify wound dressings (solid, gel, cream, or ointment dressings) and liquid wound washes containing antimicrobials as Class II or Class III medical devices. Wound dressings and washes containing antimicrobials of low or medium level antimicrobial resistance (AMR) concern would become Class II devices, whereas wound care devices containing antimicrobials of high level AMR concern would become Class III devices. To date, the majority of these unclassified devices have required a 510(k) to bring them to the U.S. market. Based on the proposal, wound dressings and washes determined to be Class II devices would need to comply with new labeling requirements and special controls, including specific performance testing and risk assessments, within 6 months of the final rule. Those devices determined to be Class III devices would require a notice of intent to file a PMA within 90 days and a PMA would need to be submitted within 30 months of the final rule. FDA published the proposed rule on November 30, 2023, and is expected to respond to comments and issue a final rule within the next 1-2 years. If the proposed rule is finalized, it is likely to have a significant impact on the classification, product labeling, and testing requirements for all wound care dressings and washes containing antimicrobials. The RQM+ team will be hosting a live panel discussion on this topic "FDA's Wound Care Shakeup: Ensuring Your Products Make the Cut". Bring your questions and join the conversation as our team of FDA regulatory experts examine the proposed rule, providing valuable insights and actionable strategies to help you navigate what's next for wound care devices. 👉 Register for free here. Proposed Product Classifications FDA is proposing to classify currently unclassified, pre-amendments wound dressings and liquid wound washes containing antimicrobials and/or other chemicals. At present, these products are regulated through the 510(k) pathway, but the proposed rule would replace the current product codes associated with wound care products containing antimicrobials as a preservative or protectant to reduce microbial growth within the dressing. If finalized, the new rule would apply to wound dressings and liquid wound washes categorized based on their physical state: Solid Wound Dressings containing antimicrobials and/or other chemicals: A solid wound dressing containing antimicrobials and/or other chemicals is used to cover and protect a wound, to absorb exudate, and to maintain appropriate moisture balance within the wound. Wound Dressings formulated as a Gel, Cream, or Ointment containing antimicrobials and/or other chemicals: A wound dressing formulated as a gel, cream, or ointment containing antimicrobials and/or other chemicals is used to maintain appropriate moisture balance within the wound. Liquid Wound Washes: A liquid wound wash is a water-based solution used to mechanically irrigate and physically remove debris from external wounds. It is also used to moisten solid wound dressings to maintain appropriate moisture balance within the dressing. In terms of their regulation, devices containing antimicrobials as protectants or preservatives would be classified as either Class II or Class III medical devices depending on the level of concern around antimicrobial resistance (AMR). Wound dressings and liquid wound washes containing antimicrobials of low or medium level AMR concern would be designated as Class II medical devices, whereas wound dressings and liquid wound washes that contain “medically important” antimicrobials would be classified as Class III products. FDA intends to regulate these “medically important” devices more strictly, as they could contribute to the development and spread of microorganisms that are resistant to medically important antimicrobials, potentially further limiting clinicians' therapeutic options. Level of riskExample ChemicalsClassificationPathwayLow level of risk antimicrobialsParabens, Hypochlorous acid, Peroxide, PHMB (polyhexamethylene biguanide)Class II510(k)Medium level of risk antimicrobialsSilver, Zinc, Copper, Chlorhexidine, Benzalkonium ChlorideClass II510(k)Medically important antimicrobialsPolymyxin B, Silver sulfadiazine, BacitracinClass IIIPMA Intended Use, Indications for Use, Claims, and Labeling With the proposed rule, the FDA is looking to make it clear that the antimicrobials and/or other chemicals in these wound dressings and liquid wound washes are not intended to treat an infection. Wound dressings and liquid wound washes within the scope of the proposed medical device classification rule are expected to only contain antimicrobials that support the use of the dressing or wash; either as a preservative or as a protectant of the product (e.g., to reduce microbial growth within a solid wound dressing while in use, to prevent or reduce contamination or deterioration of the product while in its packaging, etc.). If an antimicrobial plays a role other than as a preservative or protectant of the wound care product, then it would likely be considered a combination product and assessed based on its primary intended effect and mode of action. FDA is also looking for manufacturers to be more explicit with regard to the intended use of their antimicrobial-containing wound care product. Historically, manufacturers of these wound dressings and liquid wound washes have stated that the intended use of their device is for “wound management” and/or to reduce a patient’s “risk of infection.” With the proposed rule, manufacturers would be expected to no longer use general or misleading terms, and instead provide product labeling that explicitly states the intended use of the device (e.g., to cover and protect a wound, to absorb exudate, to maintain appropriate moisture balance, etc.). Manufacturers of wound care products already on the market may need to revise their product labeling to clarify the intended use of their device, as well as their claims. Key claims that would not be available, would require specific clarifications, or would require evidence in the form of clinical data include: Use of the term “wound management” Use of the word “may” (e.g., “may reduce the risk of infection”) Claim that the device is a treatment or cure for wounds Claim that the device delivers antimicrobials to the wound Antimicrobial preservative claims (for a sterile, single-use product), and Preservative effectiveness claims (for wound dressings formulated as a gel, cream, or ointment, and liquid wound washes) The following key claims are considered recognized benefits of the wound dressings and liquid wound washes according to the proposed rule: Maintain a moist wound healing environment Provide an effective barrier to environmental contaminants Reduce microbial growth within the dressing Extend the shelf life of nonsterile and/or multiuse wound dressings By clarifying the intended use of the antimicrobial(s) and/or other chemicals in the product’s labeling and the Indications for Use statement, wound dressings and liquid wound washes would be regulated only as “devices” and not as combination products. If a manufacturer continues to or would like to make certain wound management claims, then they may be considered a combination product or drug and regulated as such. Special Controls for Class II Devices FDA has proposed a number of special controls as part of the new rule, which would require compliance within 6 months of the new rule being finalized. Depending on the wound care product, newly classified Class II wound dressings and liquid wound washes may be expected to provide additional performance testing and descriptive information, antimicrobial characterization and preservative effectiveness testing, an AMR risk assessment, additional biocompatibility evaluation, a risk management assessment for animal-derived materials and/or botanical extracts, updated labeling, shelf-life validation, and sterilization validation. With respect to antimicrobial characterization and performance testing, FDA may expect to see performance data demonstrating that the antimicrobial has a purpose and is present in appropriate amounts to perform as intended. Testing would likely include establishment of the antimicrobial’s Minimum Effective Concentration (MEC) in the context of the final wound dressing, preservative effectiveness testing, and characterization of bioburden. With regard to providing an AMR risk assessment, FDA will likely expect an evaluation and identification of any probable risks that the device could promote the development and spread of antimicrobial resistance. FDA would also likely expect to review specific risk management assessments for certain materials like animal-derived substances and botanical extracts. Proposed Timelines For wound care devices proposed to be classified into Class II that have prior 510(k) clearance, FDA will likely expect a new 510(k) to demonstrate compliance with newly established applicable special controls. The evidence of compliance would be expected within six months of the effective date of the final rule unless the manufacturer had already provided similar or applicable data to FDA in a prior 510(k) Premarket Notification. If the new rule is finalized, manufacturers of any newly classified Class II wound products would be expected to comply with all special controls and publicly state how the product meets those special controls as part of the product’s 510(k) Summary. For wound care devices that are proposed to be classified into Class III, a notice of intent to file a PMA needs to be submitted within 90 days of the effective date of the order. FDA expects that manufacturers of Class III devices will submit a PMA within 30 months.  Conclusions The FDA's proposed rule supports greater regulation over medical devices that contain antimicrobials and other chemicals, even if they are only present to help preserve or protect the device, given their potential risk to patients and concern around increased AMR. Manufacturers of wound dressings and liquid wound washes that include antimicrobials or other chemicals should evaluate whether the new rule will impact their products. It is important to determine whether a current marketing authorization is sufficient to meet the new rule, and if not, understand what action would be required to comply with the proposed special controls. Companies with questions around the proposed new rule or in need of support determining how the proposed new rule may impact their product’s current marketing claims should feel free to reach out to RQM+. We are here to help! Don't miss our RQM+ Live! online panel discussion on FDA's Wound Care Shakeup. It could be your key to understanding the potential implications of this rule on your products and to prepare for the changes. Register for free here. #### Finding Clinical Trial Support for Different Therapeutic Areas Clinical trials are the cornerstone of medical innovation, offering pathways to groundbreaking treatments and life-saving interventions. However, the intricacies of designing and executing these studies vary significantly across therapeutic areas, demanding specialized expertise. For sponsors navigating these challenges, RQM+ provides the comprehensive support needed to ensure success. With deep expertise across diverse therapeutic areas, we deliver tailored solutions that address scientific rigour and regulatory compliance. Why Specialized Support Matters in Clinical Trials Each therapeutic area presents unique challenges, from patient recruitment to regulatory compliance. Oncology trials demand precise endpoint definitions, while neurology studies require innovative approaches to subjective data collection. Respiratory care studies often involve intricate monitoring of pulmonary function and patient-reported outcomes, while infectious disease trials face hurdles in managing evolving pathogens and global variability. Women’s health studies require sensitivity to demographic diversity and lifecycle-specific conditions. Overcoming these complexities necessitates a partner with specialized expertise, advanced methodologies, and a proven track record of success across a wide range of therapeutic areas. Key Challenges in Therapeutic-Specific Clinical Trials Oncology: High complexity, patient recruitment hurdles, and evolving endpoints. Respiratory Care: Diverse conditions like asthma and COPD necessitate targeted solutions. Neurology: Complex datasets integrating wearable technologies to detect desired signals RQM+ navigates these challenges, delivering robust data collection, regulatory alignment, and patient-centric trial designs. RQM+ Expertise Across Therapeutic Areas Oncology: Accelerating Breakthroughs in Cancer-related Trials Cancer trials are exceptionally complex, driven by the need to address diverse subtypes and integrate precision medicine into study designs. Patient Recruitment: Identifying individuals with specific biomarkers, often narrowing eligibility and requiring targeted outreach strategies. Endpoint Definition: Balancing clinical relevance with statistical rigor, utilizing metrics like progression-free survival or minimal residual disease. Regulatory Navigation: Managing the complexities of evolving guidelines, such as FDA oncology guidance and accelerated approval pathways. RQM+ tackles these challenges with tailored strategies and deep oncology expertise to streamline trial success. Respiratory Care: Advancing Solutions for Breathing Disorders Respiratory trials are critical, with millions affected by conditions like asthma and pulmonary fibrosis, requiring innovation and efficiency in every phase. Trial Design: Crafting studies tailored for new inhalation devices and cutting-edge therapies. Regulatory Compliance: Ensuring adherence to complex global standards and evolving guidelines. Patient Recruitment: Engaging diverse patient populations to generate representative and meaningful data. Neurology: Addressing the Complexities of Brain Health Neurological trials, addressing conditions like Alzheimer’s and epilepsy, face distinct hurdles stemming from subjective endpoints and the brain’s complexity. Wearable Technology: Integrating real-time data collection to improve precision and monitoring. Patient-Centric Designs: Enhancing engagement through innovative and adaptive trial approaches. Subjective data: Ensuring patient-reported outcomes align with quantitative measures Other Therapeutic Areas: Urology: Addressing conditions like prostate cancer and urinary incontinence with precision methodologies. Women’s Health: Designing sensitive trials for reproductive and menopausal health. Orthopedics and Spine: Supporting trials for innovative surgical devices and biologics. Wound Care: Providing robust methodologies for evaluating treatments for chronic wounds and burns. Ophthalmology: Ensuring precision in trials for vision care advancements. The RQM+ Approach to Clinical Trial Support At RQM+, we employ a unique, tailored approach to clinical trials, ensuring every study meets sponsor-specific goals and therapeutic area needs. Our methodology includes: Patient-Centric Trial Design: Ensuring trials are inclusive, ethical, and efficient. Seamless Regulatory Navigation: Navigating global regulations with precision. Data-Driven Insights: Leveraging advanced analytics to optimize trial outcomes. Tailored Solutions for Every Sponsor’s Needs No two trials are the same, and RQM+ understands the importance of customization. Our services include: Protocol development and optimization. Ethical oversight and regulatory submissions. Post-trial monitoring and reporting. These tailored solutions ensure that sponsors achieve both clinical and commercial success. Partnering for Success in Clinical Trials Finding the right support for clinical trials across therapeutic areas can be the difference between success and stagnation. With RQM+, sponsors gain a trusted partner with the expertise, tools, and dedication to navigate the complexities of clinical trials. Let’s advance healthcare together. Contact RQM+ today to learn how we can support your clinical trial needs and deliver transformative solutions to patients worldwide. #### Future-Proofing Sterilization: Understanding EPA's New EtO Standards and What To Do Now The EPA published a final rule this year requiring EtO sterilization facilities to significantly reduce EtO emissions. Since EtO sterilization is used for approximately 50% of sterile medical devices (estimated at over 20 billion devices sold in the U.S every year) [1], this rule has implications for both sterilization facilities and medical device manufacturers. Summary of Final Rule The EPA final rule published April 5, 2024, requires EtO sterilization facilities to reduce the amount of EtO emissions by over 90% within the next 2 to 3 years. The EPA documents indicate there are approximately 90 existing commercial sterilization facilities in the United States owned and operated by approximately 50 companies impacted by this final rule. Currently, it is estimated that approximately 10% of facilities already meet the final rule's emission standards. Impact on Sterilization Facilities and Manufacturers The implications of this rule are far-reaching. US-based sterilization facilities must install new equipment and possibly reconfigure their operations to comply. This will likely result in increased costs and reduced sterilization capacity, affecting the availability of sterilization services for medical device manufacturers. Manufacturers, on the other hand, may need to: Revalidate their sterilization processes Identify additional EtO sterilization facilities to ensure their operations are not disrupted Consider alternative sterilization methods Perform additional packaging and device testing Notify regulatory bodies about these changes *** 🎟️ Join RQM+ on July 18th for the panel discussion, Beyond EtO: New EPA Regulations and Sterilization Alternatives. Secure your spot here. *** Alternatives to EtO EtO's popularity and widespread use is primarily attributed to its efficacy in sterilizing larger volumes of devices that are sensitive to heat and moisture, such as devices containing plastic. While alternative methods are available, these are not as well established and/or have limitations, such as material incompatibility and scalability issues. Radiation is a common sterilization method that can handle large volumes of devices, but it is not suitable for all device materials. While the FDA recently announced that Vaporized Hydrogen Peroxide (VHP) is now considered an established Category A sterilization method [2] and ISO  22441:2022 is listed a recognized consensus standard by the FDA [3], it is not necessarily a one-to-one replacement for EtO because it is a vapor and not a gas. This means that the vapor does not have the same penetration capabilities as a gas, and it is incompatible with cellulose-based materials and highly absorbent materials (e.g. devices cannot be boxed in commonly used cardboard cartons whilst being sterilized). The VHP process does not currently have a comparable throughput when compared with EtO, in part because it uses smaller chambers. Other alternatives include chlorine dioxide, nitrogen dioxide, and steam. What Should Device Manufacturers Do? Manufacturers who are currently using EtO need to consider identifying multiple sterilization facilities and “softening” the EtO cycle. From a risk-based supply-chain management perspective, validating EtO at other facilities will mitigate the risks associated with facilities getting shut down and inadequate volume. Softening the EtO cycle would reduce the EtO residuals and may not require retesting of devices or packaging since the original testing may be considered a worst case. Manufacturers developing new devices should consider looking at alternative sterilization methods as described above. Radiation should be the first option to consider but it may not be appropriate due to material incompatibility. Vaporized Hydrogen Peroxide (VHP) seems to be the next best choice but may not be suitable for higher volumes.  To help navigate these changes, RQM+ is hosting a panel discussion on July 18th. This session will provide a comprehensive analysis of the new EPA rule and offer actionable strategies for compliance and exploration of alternative sterilization methods. You can ask your own questions, too. Key Topics: Impact Assessment: Detailed insights into how the new EPA rule affects EtO sterilization facilities and medical device manufacturers. Compliance Strategies: Practical guidance on adjusting EtO cycles, setting up new EtO sites and identifying alternatives. Alternative Sterilization Methods: An overview of viable alternatives, including their pros and cons and validation processes. Industry Perspectives: Overview of what we are hearing from industry stakeholders and examples of how companies are adapting to these changes. Why Attend? This panel discussion is ideal for regulatory affairs professionals, quality engineers, manufacturing leaders, and medical device manufacturers who rely on EtO sterilization or are considering alternative methods. Attendees will gain: A clear understanding of the new EtO regulations impacting the US-based facilities. Practical steps to take as a result of these new regulations. Insights into alternative sterilization methods and their implementation. Strategies to ensure your products remain safe and market-ready. Count Me In [1] FDA News Release. FDA Facilitates Broader Adoption of Vaporized Hydrogen Peroxide for Medical Device Sterilization. Agency Continues to Encourage Ethylene Oxide Sterilization Alternatives (8th Jan 2024) https://www.fda.gov/news-events/press-announcements/fda-facilitates-broader-adoption-vaporized-hydrogen-peroxide-medical-device-sterilization [2] Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile (8th Jan 2024) https://www.fda.gov/media/74445/download?attachment [3] ISO  22441:2022, First edition; Sterilization of health care products - Low temperature vaporized hydrogen peroxide - Requirements for the development, validation and routine control of a sterilization process for medical devices (FR Recognition List 060, 29th May 2023) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/detail.cfm?standard__identification_no=4429 #### Global Perspectives: Comparing Regulations for Point of Care Tests in the U.S. and EU Point of Care tests (POCT) is a term that is widely used to describe IVDs that are used at the same location as the patient, as opposed to an IVD that is used within a laboratory. This can include a wide range of locations including doctor's offices, clinics, patient bedside, near-patient settings, or other locations outside of a traditional laboratory. POCTs have gained popularity globally as they provide faster results to the patient and can help inform patient management decisions without the delays involved in transferring a sample between a patient location (e.g. doctor's office or hospital) and the reference laboratory. Note that a POCT is different from a test for home use (also called a self-test, or over the counter test), where the patient can directly access and use the test within their home environment. With the increased demand for POCTs, there has been an increase in investment from MedTech companies to design and develop new POCTs that cover a wider range of analytes and can be utilized in a variety of healthcare settings. The development of new tests necessitates that these tests also must go through regulatory approval for the relevant geographic regions.   In this technical brief, we will explore the complexities of bringing POCTs to market through a comparison of the difference in regulatory requirements between the U.S. FDA and EU IVDR. Point of Care Tests in the United States In the U.S., FDA categorizes IVDs according to their complexity. There are three levels of complexity that are determined by FDA after the IVD is cleared: high complexity, moderate complexity, and waived tests. These complexity levels correspond to the type of laboratory that may run the test. The laboratories are certified under the Clinical Laboratory Improvement Amendments (CLIA) program for a certain complexity level: High complexity, moderate complexity, and CLIA waived. Moderate and high complexity laboratories are subject to inspection, and must meet CLIA quality system standards, quality control and assessment, and personnel requirements.  In contrast, a testing site that only wants to run waived tests would not need to meet the requirements of moderate or high complexity and would instead require only a certificate of waiver from CLIA [1] [2]. A POCT may be categorized as either a moderate complexity or waived test. The appropriate complexity for the test depends on several factors including complexity and risk of erroneous results. When the POCT is designed, the manufacturer must consider whether it can meet the requirements of a waived test as outlined in FDA guidance documents [3] [4] [5]. The complexity of the test, and inclusion of the test requirements for waived tests must be included up front during design and development to ensure that the device can ultimately be cleared at the expected CLIA level. ▶ Watch the panel discussion now: Advancing Health Equity with IVDs & Medical Devices POCT in the EU In the EU, POCT are not recognized as a type of test under the EU In Vitro Diagnostic Regulation (IVDR). Instead, the term "device for near-patient testing" is used [6]. The IVDR defines near-patient tests (NPTs) as any device that is not intended for self-testing but is intended to perform testing outside of a laboratory environment, generally near to, or at the side of, the patient by a health professional. Unlike in the U.S., there is no laboratory designation level akin to CLIA associated with this type of test. It is typically expected to be used outside of a laboratory environment, but by users who would not be considered "lay persons" but rather "healthcare professionals" such as nurses and physicians. The IVDR outlines requirements for tests that meet the definition of an NPT. This includes specific labeling requirements as well as design requirements. As with all devices, the IVDR requires that NPTs are designed and developed for the intended purpose, which must be demonstrated through the performance evaluation. For NPTs, this includes a design that considers the competence of the user, as well as instructions for use that are appropriate for the user to apply in order to correctly run the test and interpret the result (GSPR 19). These tests must also account for variation that can be reasonably anticipated in the intended users’ technique and environment. Performance evaluation is expected to include clinical performance in the hands of the intended user, as well as usability studies to ensure that the test can be used as intended. Bridging the Differences Between EU and US POCT Regulations For companies looking to gain market access in both the U.S. and EU, the regulatory pathway within one geography may or may not align with the other. Different potential scenarios are outlined below: Scenario 1: An IVD for rapid detection of Strep A in throat swabs is CLIA waived by FDA and considered a NPT under IVDR. Scenario 2: A POC Clinical analyzer is CLIA waived in the U.S. for use in POC healthcare settings and is an NPT under IVDR. Scenario 3: A rapid molecular test for identification and differentiation for respiratory infection is moderate/high complexity under FDA and an NPT under IVDR. Due to the differences in regulation between U.S. and EU, manufacturers of POCT need to be especially careful that the differences in users are considered when planning clinical studies. For Scenario 1, a CLIA-waived test in the U.S. does not have any user training requirements associated with it beyond the test instructions. This is in contrast to an NPT in the EU, which would require that the user be "healthcare professionals", and that specific qualifications and training are outlined in the IFU. In the case of a test that is moderate complexity in the U.S., but an NPT in the EU, the opposite problem exists. In the U.S. the POC setting must be CLIA certified, requiring specific training for users as well as a quality system. This is different from an NPT in the EU as IVDR does not have any specific user training like under a CLIA certification, but rather allows the legal manufacturer of the IVD to set their own requirements. There are also no quality system requirements for sites using IVDR certified NPTs. It is important to consider how the differences in the regulatory landscape and intended user within each of the geographies impacts the design and development pathway for the device. While it can be complicated to design and validate an IVD to support multiple geographies, planning and considering regulatory requirements early in the process will support more efficient market access. The following activities will help outline the path forward for a given POCT. Consider POCT classification in both geographies early such that appropriate design controls can be included up front. For example, CLIA waived will require more simplistic operation versus a test that is cleared for use in a moderate complexity laboratory. The IVDR has requirements regarding the design including a warning if the device has failed to provide an accurate result (GSPR 19.3). Consider how performance data from the same clinical study can be leveraged for multiple geographies. In order to leverage data across both U.S. and EU, the clinical trial must be designed in such a way to demonstrate both regulatory scenarios. This may mean running a multi-country clinical trial with sites in both the U.S. and EU. It could also mean collecting information regarding the users within the U.S. clinical study to demonstrate that the appropriate "healthcare professionals" are included to support EU market access. Both FDA and EU notified bodies will expect that the clinical data presented accurately reflects the intended use within their geography, so a combined study needs to be carefully executed to ensure that all requirements are included and that the proper details are gathered to support the indications. Consider running separate usability studies. The differences in regulatory requirements for labeling as well as intended user demographics in each geography can be mitigated by running separate usability studies, which will help to demonstrate the acceptability of the test for the desired user within each geography. Additionally, the different geographic regions may require different labelling, which should be verified through a usability study. It is good practice to perform summative usability studies prior to starting a prospective clinical study to allow for design changes in response to the outcome of the usability study prior to the pivotal trial. In the case where a usability study identifies systematic design issues that must be corrected, making these changes prior to the pivotal trial is ideal to avoid additional clinical studies to bridge the design changes. Conclusion Navigating the regulatory landscape for POCTs across both the U.S. and the EU requires careful planning and a clear understanding of the unique requirements in each region. While the U.S. CLIA system categorizes tests based on complexity and imposes specific quality and training standards, the EU's IVDR has no clear standards for sites and focuses more on device design and performance in the intended use setting by healthcare professionals. Manufacturers must address these regulatory differences early in the design and development process, ensuring that clinical studies, usability testing, and labeling requirements align with both U.S. and EU standards. By anticipating and integrating these diverse requirements, companies can streamline their path to market and ensure that their POCTs are safe, effective, and accessible in multiple regions. The good news is that we are here to help! Our experts know the ins and outs of bringing POCTs to the market and keeping them there, so contact us today to learn more. 💡 Sign up now: Structured Dialogue: How to Engage with Notified Bodies Sources: [1] CDC, "Test Complexities," [Online]. Available: https://www.cdc.gov/clia/php/test-complexities/index.html[2] FDA, "CLIA Categorizations," [Online]. Available: https://www.fda.gov/medical-devices/ivd-regulatory-assistance/clia-categorizations[3] FDA, "Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices," [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-clinical-laboratory-improvement-amendments-1988-clia-waiver-applications.[4] FDA, "Recommendations for Dual 510(k) and CLIA Waiver by Application Studies," [Online]. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-dual-510k-and-clia-waiver-application-studies.[5] FDA, "CLIA Waiver by Application," [Online]. Available: https://www.fda.gov/medical-devices/ivd-regulatory-assistance/clia-waiver-application.[6] "EU Regulation 2017/746 In Vitro Diagnostic Regulation," Official Journal of the European Union, 2017.  #### Good Manufacturing Practice in the Medical Device Industry All manufacturers are expected to establish some form of quality protocols to ensure that products meet a minimum standard, whether that threshold is established by general expectations or by regulators. Naturally, manufacturers of medical devices are held to a higher benchmark than producers operating in most other markets. Various regulators have established frameworks that set out minimum levels of quality in the design and production of medical devices, but in the US, it is the Food and Drug Administration (FDA) that primarily governs medical device quality via their umbrella approach to good manufacturing practices (GMP). What is GMP and How Does it Apply to Medical Devices? Good manufacturing practices are a set of formal specifications established by the FDA and other global regulators with the goal of setting a minimum quality benchmark for products in critical markets. Sometimes referred to as current good manufacturing practices, or cGMP, these standards are a flexible set of requirements designed to ensure that all medical devices released to market are safe and effective. According to the FDA, a medical device constitutes: “An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is…intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.” So the remit of GMP medical devices runs a wide gamut, from simple personal protective equipment (PPE) like surgical masks, through to high-technology implantables, such as valves or stints. This makes it impossible for a single regulator to set-up individual good manufacturing practices for each product type—hence the aforementioned umbrella approach. What is the Umbrella Approach of GMP Medical Devices? The umbrella approach to cGMP refers to the flexibility embedded into the FDA’s quality protocols. It is less a series of prescribed standards and more a framework mandating that manufacturers develop and follow their own quality protocols appropriate for a given device, using state-of-the-art manufacturing techniques and acceptable QA/QC parameters. This means that a GMP program will influence every step in the medical device development chain, from employee hygiene through to record-keeping. Developing Good Manufacturing Practices with RQM+ Lab Services At RQM+ Lab Services, we have years of experience working to exceed the necessarily strict regulatory standards for medical device manufacturing, offering GMP-compliant analytical services. Our goal is to help customers ensure due-diligence is carried out throughout the manufacturing pipeline to eliminate any margin of error and guarantee good manufacturing practices are adhered to. We achieve this by offering complex GMP-compliant solutions which can add value to your production cycles by providing actionable data where you need it most. This not only saves you time and money on costly product recalls and speculative QA/QC testing, but ensures you routinely go beyond the minimum requirements to provide highly safe and effective medical devices. Source:https://www.fda.gov/medical-devices/classify-your-medical-device/how-determine-if-your-product-medical-device Further reading - 5 Key Elements of GMP in the Food Industry #### Greenlit in Europe, Grounded in America: A Medtech Paradox Despite growing complaints that the EU-MDR is choking MedTech innovation, recent regulatory outcomes reveal a more complex truth. Several medium- and high-risk devices, such as Boston Scientific’s ACURATE valve and Becton Dickinson’s Phasix mesh, have earned CE marking under the MDR, yet failed or stalled in the U.S. due to lacking clinical evidence - illustrating the need for robust, globally-aligned regulatory strategy and evidence planning. This article argues that innovation isn’t being stifled by MDR; it’s being redefined through a framework of transparency, post-market evidence, and proportionality. If innovation is struggling, it may be due to resistance against these evolving standards, not the standards themselves.  Approved in Europe, Denied by Data: When Innovation Outruns Evidence Why this matters? Patients: Your access to innovation depends on where you live, not what you need. Innovators: The regulatory “fast lane” isn’t always where you think it is. Policymakers: The real question isn’t “Who’s faster?”, it’s “Who’s right?”  Introduction: Welcome to the Transatlantic Irony   In an era where regulatory narratives have flipped on their heads, the commonly recited lament that “EU-MDR is stifling innovation” is starting to sound suspiciously one-note. As a former Technical Team Leader at BSI and now as the VP of Global Regulatory Affairs at RQM+, I’ve seen devices hailed as breakthroughs in Europe rejected outright in the U.S. for lack of data. That’s not just irony; it’s a transatlantic regulatory riddle worth decoding.  This isn’t the fringe; it’s happening with headline-grabbing devices. Take Boston Scientific’s ACURATE neo2/Prime transcatheter aortic valve (TAVR), for example. CE-marked under MDR yet tripped on its own clinical data enroute to FDA approval. And that’s just one case.  We’re overdue for a real conversation: Is the EU-MDR really the enemy of innovation, or is it exposing where innovation is outpacing evidence? Is the FDA’s bar the gold standard, or is it sometimes missing a chance to learn from real-world experience? When a prophylactic indication gets approved in the EU with weak data and perhaps conditional post-market surveillance, we have to ask: who’s doing it right?  This article is the counterpoint to the hand-wringing. Let’s dismantle the myth that innovation thrives only where the red tape is thin. If this is what stifling innovation looks like, maybe we should ask what ‘safe innovation’ actually means.  Approved But Not ACURATE: CE Marked but Clinically Inferior? Boston Scientific’s ACURATE Prime valve received its CE Mark under MDR in August 2024, after years of use in Europe (Neo, Neo2 versions under the prior directive) and before completion of the pivotal U.S. trial. Of note, there were two earlier randomized controlled trials, SCOPE 1 and SCOPE 2, conducted between 2017 and 2019, where ACURATE failed to meet its primary endpoint.  Importantly, CE marking was granted before the IDE trial results were fully analyzed and published. This reveals something more nuanced than a binary approval-failure paradox. Rather than being approved in spite of a failed trial, ACURATE was approved without the pivotal trial at all, highlighting the flexibility, or perhaps vulnerability, of the EU’s risk-based system.   The IDE trial later revealed a 16.1% event rate for ACURATE versus 9.5% for Edwards Sapien and Medtronic Evolut, a significant clinical miss [1]. But by then, the device had already been CE marked. Critically, the post-market story in Europe is richer than a single trial. BSC and its Notified Body can consider real-world evidence (RWE) from thousands of European patients, which may present a different narrative than tightly controlled U.S. trials. That’s both the strength and the question mark of the EU model: earlier access, broader inputs, but sometimes, less certainty.  How is a device that couldn’t match standard-of-care outcomes in a tightly controlled U.S. trial considered safe and effective enough in the EU?  Let’s be clear: innovation isn’t being stifled here. It was perhaps let loose too early. The ACURATE saga illustrates that CE marking, even under the supposedly stricter MDR regime, still permits devices with underwhelming performance, provided there’s sufficient justification and a roadmap for improvement. The FDA, however, isn’t buying it. Clinical evidence mattered more than procedural simplicity or ease of deployment.  Europe gave these devices a head start. The FDA made them prove they were worth it. Both were right and wrong. Approved doesn’t always mean proven. In this case, it means premature.  The Mesh That Slipped Through: Off-Label Data, On-Label Approval Case in point: the bioabsorbable Phasix mesh. Originally approved for hernia repair, the manufacturer sought to expand the indication to prophylactic use with off-label use data. The expert panel triggered by MDR Article 54 wasn’t thrilled. They cited inadequate long-term data, lack of comparative studies, and concerns from prior safety flags [2].  Yet the device was approved anyway. Notified bodies justified the decision and CE marked the expanded indication albeit with stringent post-market follow-up requirements. The irony? The U.S. FDA would have likely sent that application back with a red pen and a polite “try again.”  This is not a case of MDR throttling innovation. If anything, the system flexed to allow a novel clinical use leveraging off-label use data. It's exactly the kind of nuanced, market-aware regulation, innovation should thrive under; provided it doesn't forget the guardrails. And in this case, the MDR relied heavily on transparency and PMCF to de-risk the decision. Whether that’s visionary or reckless depends on what the five-year data reveals. So, was the EU premature or pragmatic? Ask again in five years if the patients don’t answer first.  Paper Cuts or Patient Wins? When MDR Documentation Becomes the BoogeymanGreen Lights in Europe, Red Tape in the U.S.  Let’s admit it: MDR is a paper monster. The volume of documentation required for compliance can feel punitive. But here’s the twist, it’s not just about red tape for red tape’s sake. Much of this documentation, particularly the periodic safety updates, clinical evaluation reports, and PMCF plans, feeds directly into transparency and accountability. These were deliberate reactions to scandals like the PIP breast implant fiasco and the metal-on-metal hip debacle.  Does this documentation always make a device safer? Not directly. However, driven by the need to meet MDR requirements and Notified Body requests, manufacturers are not only staying close to real-world data but they’re also finding innovative, often creative ways to do so. As a result, we’re seeing outcomes from a broader, more diverse patient population than ever before. And, like it or not, in a competitive landscape, transparency becomes a differentiator. Your competitor may be using their documented outcomes to win over hospitals and health authorities. In the MDR, compliance is a survival skill, and, paradoxically, a tool for competitive innovation.  Transparency might not be convenient, but it just might be revolutionary.  Green Lights in Europe, Red Tape in the U.S.  Comparative looks at how some key devices navigated the EU vs. U.S. regulatory gauntlet: one eventually found shelter in FDA’s house, but the rest are still knocking or napping on the porch.   Device EU StatusFDA Status Evidence GapMDR Risk Class ACURATE neo2 and ACURATE Prime (Boston Scientific) CE Marked (MDR) (2024) IDE trial failed, 2 other RCTs failed; not approved, currentlyFailed non-inferiority endpoint Class III Phasix Mesh (BD)CE Marked (2024, prophylactic use) No FDA indication expansion Weak long-term, non-comparative data Class III Neovasc Reducer (Shockwave) CE Marked (2011)Rejected by panel (2020); new U.S. trial ongoing Small trial, subjective endpoints Class IIIneuroAD System (Neuronix) CE Marked Rejected in 2019No benefit over sham in RCT Class IIb M6-L Disc (Orthofix) CE Marked (2006)Never submitted (the lumbar version) No FDA trial; costly IDE requirements Class III CMR Versius Robot CE Marked (2019) FDA cleared in 2024 (De Novo) Delay due to pathway complexity Class IIb  Each of these cases presents a lesson in regulatory divergence, not deficiency. Innovation wasn’t blocked in Europe; it was conditionally allowed, often with rigorous follow-up commitments. The U.S. path, meanwhile, demanded premarket certainty.  Some devices fly on real-world experience, others stall on missing data. The runway you choose matters.  What the Next Decade of Innovation Needs from RegulatorsConclusion: Innovation Demands Evidence, Not Expediency As MedTech complexity accelerates, the regulatory frameworks that govern them must evolve; not just to keep up, but to lead responsibly. The future belongs to systems that reward designed-in evidence, not post-hoc justifications. Regulators must double down on:  Data interoperability: Leveraging international real-world evidence (RWE) and post-market registries.  Global convergence: Aligning on definitions, endpoints, and risk thresholds across FDA, EU, and IMDRF partners.  Modular approvals: Enabling conditionally approved indications tied to PMCF or additional cohorts.  To serve patients and foster meaningful innovation, we must move from regionally bounded decisions to globally informed regulation. The EU and U.S. don’t need to match timelines, they need to align on what good evidence looks like.  But here’s another wrinkle worth unpacking: Clarity.  In the U.S., manufacturers can proactively engage the FDA, receiving structured feedback on clinical strategy, trial design, and evidentiary expectations through formal mechanisms. In the EU, manufacturers of high-risk devices may approach the Expert Panel for guidance, but those comments are non-binding. The final authority lies with the Notified Bodies, and this is where the real structural tension emerges. Unlike the FDA, which is a single regulatory body, the EU relies on a decentralized network of Notified Bodies. If they were allowed to offer binding clinical strategy guidance, it would create a competitive incentive to “go easy”, undermining consistency and lowering the bar. As a result, manufacturers are left to guess at expectations and over-engineer technical files just to hedge against opacity.  So we have to ask: is innovation slowed by the quantity and quality of evidence, or by the uncertainty of what will be accepted? That ambiguity doesn’t just delay timelines; it distorts strategy. If the next decade of innovation is to thrive, regulators must pair rigor with transparency. Otherwise, we’re not regulating innovation; we’re gambling with it.  Conclusion: Innovation Demands Evidence, Not Expediency The idea that EU-MDR stifles innovation has become regulatory folklore. But look closer, and the story crumbles. CE-marked devices like ACURATE and the Phasix mesh prove that the MDR still makes room for innovation, sometimes at the expense of rigor. Meanwhile, the FDA’s higher bar keeps certain innovations out, but not always unfairly.  Innovation doesn’t thrive in a vacuum or an absence of regulation. It thrives in proportionate, informed, and evidence-driven environments where transparency isn’t optional, and real-world outcomes matter more than regulatory shortcuts.   The MDR isn’t perfect; it’s bureaucratic and resource-intensive. But it’s also trying to do something regulators rarely do: demand proof without stalling progress while emphasizing transparency. If innovation is being stifled, perhaps it’s not by regulation but by the refusal to meet its rising expectations. Maybe just maybe, the real innovation isn’t the device itself; it’s designing clinical evidence into the blueprint, not bolting it on after launch.  Regulators aren’t gatekeepers of progress. They’re stewards of trust. And trust like data can’t be faked. If we want innovation that matters, we must stop blaming the rulebook and start rewriting the playbook.  The future of MedTech won’t be written by those who got there first; it will be written by those who proved they belonged.  Contact Us Interested in learning more how to shape your clinical and regulatory strategy? Contact us today. Our friendly team at RQM+ is ready to assist you in addressing geo-strategic questions and ensuring your innovative MedTech products reach patients who will benefit from it. We're here to make your MedTech happen! #### Hearts in a Bind: Choosing Between Promise and Predictability Roses Are Red, Your Valve’s Askew, TAVR’s the Cue That’s Tried and True?  Meet Clara, 72, who traded aortic stenosis-induced fatigue for morning walks with her grandkids, thanks to TAVR's minimally invasive magic. TAVR (transcatheter aortic valve replacement) isn’t just a medical acronym, it’s the ultimate rebound for your heart, ditching the “crack-the-chest” melodrama for a catheter-based precision strike. Think of it as cardiac care’s greatest hits remix: Shorter recovery Fewer complications A VIP pass for high-risk patients once labeled “surgically un-dateable” by traditional standards Aortic stenosis? It’s the clingy, toxic ex who won’t stop texting. TAVR? The no-nonsense hero swiping left on stenosis and restoring blood flow with precision. But before you commit, let’s ask: Will this heartthrob even outlast your smartphone, or will durability data ghost you faster than a Tinder match? Only time and durability data will tell. Valve Wars: Balloon vs. Self-Expander – Who’s the Real MVP of Your Heart?(Data Transparency: It’s Messy) Relationships thrive on trust, but with TAVR data, it’s like dating someone who forgets their ex exists when it’s convenient. Transparency is a must. Recent six-year data reveals a plot twist: mortality rates diverge between valve types¹,². Self-expanding valves, the free-spirited rebels of the TAVR world, might promise flexibility but come with a catch: higher long-term mortality compared to their balloon-expandable cousins, the meticulous planners of the valve universe. Cue the transparency alarm; delayed data reporting on the balloon-expandable platform is the villain here, lurking in the shadows like a bad sequel. Frankly, discrepancies in long-term mortality rates between valve platforms are raising eyebrows, and without comprehensive data, informed decision-making is about as reliable as a fortune cookie’s relationship advice. Let’s demand clearer stats, because guessing games belong in casinos, not operating rooms (OR). After all, when it comes to valves, “trust me, bro” isn’t a valid surgical strategy. To the engineers, clinicians, and researchers: Every valve you refine, every dataset you scrutinize; it’s not just science. It’s a lifeline.  Durability Déjà Vu: TAVR’s durability isn’t a fling, it’s a slow dance where every year counts. Every love story needs longevity. TAVR’s? Still auditioning for ‘The One.' Early data? Promising. Five-year mark? Still murkier than a Valentine’s Day fog machine. Young at heart? SAVR might be your “till death do us part,” but TAVR is the cool “let’s see where this goes” fling. Young at Heart? TAVR vs. SAVR – The Cardiologist’s ‘It’s Complicated’ Status TAVR or SAVR? It’s the cardiac equivalent of choosing between The Notebook and Eternal Sunshine of the Spotless Mind. SAVR is the classic choice for younger patients, but TAVR is the tempting “let’s postpone adulthood” option. Choosing TAVR or SAVR is like swiping left on SAVR stability for TAVR’s flair, but remember, commitment issues don’t disappear at the altar, or the operating room. Just remember, deferring surgery isn’t a magical fix, it’s just hitting snooze on the inevitable alarm. After all, it's not just about love at first implant, it's about a lifetime of commitment. Your multidisciplinary huddles aren’t just meetings, they’re the reason someone’s mom gets to blow out 80 candles. Love Calculator: Crunching Lifetime Risks (Spoiler: It’s Not Romantic) Lifetime Estimated Risk (LER)³: The surgical prenup of TAVR decision-making you didn’t know you needed. It’s an uncomfortable but necessary conversation about cumulative risks down the line. Younger patients, especially, need to know the score because no one dreams of celebrating their 60th birthday with a "valve-in-valve redo" party.  Pro tip: Always check the warranty (aka Lifetime Estimated Risk or LER). Think of LER as your valve’s Yelp review: cumulative risk scores help decide whether to commit to TAVR now or save your surgical swipes for later. TAVR’s Love Potion Is Precision-Engineered and Cupid’s Arrow Was So Last Millennium  Tailoring Precision - Why Anatomy and Risk Matter: In TAVR, one size definitely does not fit all. Think of it as tailoring a custom suit except the stakes are your life, not your prom photos. Coronary height, bicuspid valves, and annulus size complicate the decision (and aren’t just trivia), they’re the holy trinity of valve selection. Miss one, and you’re basically playing Operation with real hearts. A Clearer Picture - Imaging for Love (and Longevity): Love may be blind, but successful TAVR outcomes require 20/20 vision, figuratively speaking. Multidisciplinary valve teams and high resolution imaging (like gated CT scans) are the dynamic duo of patient evaluation ensuring the best fit between valve and patient. Imagine Batman (the cardiologist) and Robin (the radiologist) teaming up to vanquish aortic stenosis! Or call it the eHarmony of interventional cardiology, matching anatomy with technology. iValve Pro Max: From sleeker valve designs to sharper imaging tech, TAVR’s upgrades are sleeker than Apple’s latest iPhone minus the annual upgrade guilt. Next-gen valves? They’re basically Apple’s 2050 keynote.  Next-gen valves aren’t just gadgets, they’re tiny guardians, whispering ‘not on my watch’ to stenosis. Reintervention Roulette: Bet on TAVR, But Play Smart Valve-in-valve procedures? Reinterventions are the ultimate "backup plan." Sure, it’s nice to know TAVR has a redo option, but relying on valve-in-valve procedures isn’t exactly a badge of success. They’re TAVR’s encore performance, a second act when the first implant starts phoning it in. But let’s aim for a one-hit wonder. Optimal placement and patient selection are key because nobody wants a sequel (Transformers: Age of Calcification doesn’t have the same ring). The STS/ACC TVT Registry shows reintervention rates are manageable, but let’s keep it that way. After all, repeat procedures are like reboots, sometimes necessary, rarely beloved. Heartbreak Hotel: Why Some Valves Ghost Us After Six Years Some valves ghost us faster than a bad Valentine’s Day date... 5 to 6 years, and they’re already gone! Let’s change that. Why do some valves falter long-term? It’s the cardiac community’s newest whodunit. Spoiler alert: RQM+ is on the case, blending rigorous trials, ethical grit, and a sprinkle of Sherlock Holmes to crack the code. The six-year data divergence isn’t just a plot hole, it’s a call to arms. Transparency is the magnifying glass here. No more foggy stats, let’s turn headlights on long-term outcomes and demand answers sharper than a scalpel. When valves fail, it’s not just data, it’s a patient’s hope deferred. That’s why we’re dissecting every outlier like it’s our own family’s story. RQM+: The Wingmen of TAVR Innovation(Swipe Right for Data-Driven Science) RQM+ playbook for the cardiac matchmaking algorithm? Data Transparency or Bust: We’re the Marie Kondo of clinical research, sparking joy by decluttering murky data. Patient-Centric Swagger: Your anatomy, your rules. We tailor trials like bespoke suits, because one-size-fits-all is so 2005. Collaboration Nation: Partnering with top doctors to ensure TAVR’s future is brighter than a stent in sunlight. Think of us as the Avengers of aortic innovation minus the capes (lab coats only). At RQM+, we’re not just running trials, we’re building bridges between lab benches and living rooms, ensuring every innovation earns its place in a patient’s story. Happily Ever After? Only If TAVR Keeps Its Promises (and Data)  TAVR, a life-saving Romeo with a catheter, isn’t just cardiology’s answer to a rom-com; it’s the ultimate slow burn. It dazzles with less drama (goodbye, “crack-the-chest” theatrics), restores flow like a love potion, and whispers sweet nothings like “durability data pending”. But let’s be real: even soulmates need prenups these days. For TAVR, that means LER assessments, transparent stats, and innovation that doesn’t ghost patients after year 5. TAVR’s encore isn’t just applause, it’s the sound of grandkids laughing, of weddings witnessed, of lives rewritten. This Valentine’s Day, as you prepare to swipe left on aortic stenosis, let’s skip the chocolates and demand substance over sonnets. TAVR’s future isn’t about fairy tales; it’s about valves that last longer than your last relationship, data clearer than a “we need to talk” chat, and innovation that doesn’t leave patients guessing.RQM+ isn’t just in the business of clinical trials, we’re rewriting cardiac care’s love story. Less tragic Shakespeare, more power couple. …because in the end, the best valve isn’t the one that just swoops in, it’s the one that stays. Now, let’s sync up, innovate harder, and make sure TAVR’s encore is a standing ovation. In TAVR we trust. But in RQM+? We verify. References Post-Approval Studies (PAS) Database Mortality Divergence in 6-Year Data Reshaping the TAVR vs. SAVR Debate! | LinkedIn Chen S et al. Lifetime Management for Aortic Stenosis: Strategy and Decision-Making in the Current Era. Ann Thorac Surg 2025;119:296-307. #### How a Full-Service CRO Can Get Your Device to Market Quicker From navigating the complex regulatory environment to implementing the right quality controls — MedTech companies face many challenges in getting their products to market. These challenges lengthen product development cycles and increase the time it takes to get vital technologies to the patients who need them. For many MedTech organizations, Clinical Research Organizations (CROs) are indispensable partners in solving these challenges. CROs specialize in managing different product development stages, such as medical testing or running clinical trials. Their expertise is key to accelerating timelines and getting better products to market. But dealing with multiple specialist partners can be tricky. Not only does it increase project complexity but specialists often have a poor understanding of the full MedTech product journey. As decisions made at one stage of the cycle will impact all other stages, this lack of knowledge can lead to costly choices that delay project timelines.  Introducing your end-to-end CRO for all MedTech product needs At RQM+, we offer a comprehensive, end-to-end solution that fast-tracks the MedTech product journey. With full sightlines over project execution, we can provide value at each stage of product development. This way, we help ensure a faster time-to-market without compromising on quality.  By partnering with an end-to-end CRO like RQM+, clients can expect: Unified Vision — Having a single partner guarantees consistent strategies and vision from the early stages of product development to its market entry. Efficiency & Speed — Avoid time-consuming handovers between multiple agencies. One full-service CRO means streamlined communication, faster decision-making, and reduced time-to-market. Practical Expertise — Specialized, hands-on experience at every stage, from regulatory consultants with direct experience crafting medical legislation, to clinical trials and lab services. Cost-Effective Execution — Save on costs arising from coordination between multiple vendors, reworking product strategies, and duplicated efforts. Minimized Risk — Our integrated approach ensures consistent quality checks, a unified strategy, and minimal human error. Unified Expertise — Regulatory and quality consulting, clinical trials, lab, and reimbursement services are all under one roof. One trusted partner. No missed hand-offs. No lost time. As the leading MedTech service provider with the largest global team of regulatory and quality experts, we offer a premier, single global platform for our clients — with support that extends from concept to commercialization. Our service offerings are organized into four business solutions: Regulatory and Quality Consulting, Reimbursement Services, Clinical Trials Services, and Laboratory Services.  Let’s explore how each solution can more quickly get your MedTech product to market. Regulatory and Quality Consulting: navigating the complex regulatory landscape The ever-evolving regulatory landscape can significantly slow down product development and market entry. This is especially true for those operating in multiple markets. The EU, for instance, will have different regulatory requirements than the US market.  In an environment where compliance is not an option but a necessity, MedTech companies often struggle with keeping up-to-date on ever-changing regulations, let alone strategizing for long-term success. Our specialized team comprises former regulatory body experts, known for their unparalleled expertise and influential presence in regulatory circles. They will work with you to determine the right plan of action for a successful go-to-market strategy.  Our strategies and expert guidance are tailored to your unique business needs. Whether it's strategizing for long-term market success or streamlining clinical trial execution, RQM+ helps you accelerate your regulatory compliance timelines. Reimbursement Services: securing payment and market adoption Breaking through the MedTech market is difficult enough; securing reimbursement for your innovations presents an additional set of hurdles that impact speed-to-market. Without effective reimbursement strategies, even the most promising medical technologies can struggle to gain traction. Our Reimbursement Services are designed to maximize market access and revenue potential. We will help you determine the best reimbursement system for your product while guaranteeing regulatory compliance. This includes securing proper coding, appropriate insurance coverage, and determining the most lucrative and reliable payment structure.  Clinical Trials: efficient, high-quality trials for faster approval Performing clinical trials can be one of the most time-consuming phases in MedTech product development. The difficulties here extend past regulatory concerns to include data collection and analysis challenges. RQM+ Clinical Trials services provide efficient study design and management aimed at generating high-quality, accurate, clean, and validated data on product safety and effectiveness. Our services employ agile execution strategies and digital solutions that streamline information sharing. That means that you can quickly and easily interpret clinical results.  Every Clinical Evaluation Plan we create balances regulatory, clinical, and business risks and objectives. We are uniquely positioned to help you create a strategy for presenting clinical evidence and analysis. With insights into what notified bodies are expecting, RQM+ prepares both your team and documentation to meet these stringent standards. Laboratory Services: ensuring the safety and efficacy of your products Lab testing is a critical component that can't be rushed or compromised, yet it is often a bottleneck in the product development process. Our Lab Services team is led by Ph.D. analytical chemists who employ state-of-the-art technologies and a multi-detector approach to accurately characterize MedTech materials. We don't just meet regulatory requirements; we aim to exceed them. Our comprehensive testing, analysis, and validation services support regulatory compliance while minimizing delays in product development. This minimizes risk to both end users and your company, thereby protecting your brand and reputation for the long haul. We’re also set apart by our track record of solving complex issues where other providers fall short. The factors position RQM+ as a trusted partner for fast, reliable, and above all, quality-assured lab testing. Accelerate your MedTech journey with RQM+'s end-to-end solution Partnering with a full-service CRO brings multifaceted benefits. It establishes a unified vision and strategic consistency throughout your product’s journey, ensures optimized efficiency, and swift market entry. It also provides access to diverse, specialized expertise at every developmental stage, all while providing cost efficiency and risk mitigation. #### How is MedTech Transforming Breast Cancer Care? Breast cancer is both a profound health challenge and a fast-moving arena for MedTech innovation. Survival has improved thanks to earlier detection and more precise therapies, and—crucially—new devices and software are now reshaping care from first screening through survivorship. In a recent RQM+ Women’s Health panel, survivors and regulatory experts discussed the technologies making the biggest difference today. Their perspectives ground this piece in lived experience and practical reality: innovation matters most when it is safe, effective, and reaches patients and clinicians who need it. From Detection to Decisive Action: Imaging + AI Early, accurate detection expands options and improves outcomes. Panelists highlighted how imaging advances are raising the bar: AI as a second reader in mammography is no longer theoretical. Algorithms are assisting radiologists by spotting subtle patterns beyond the human eye, localizing suspicious regions and helping target the biopsy to the right place sooner. The impact: fewer missed cancers and more efficient workflows. Ultrasound and MRI remain core tools across populations and disease stages, and AI models tailored specifically for breast imaging are being deployed on these modalities to improve specificity and reduce unnecessary recalls. On the procedural side, minimally invasive tools continue to evolve. Vacuum-assisted biopsy systems improve tissue sampling accuracy with less discomfort, and localization technologies help surgeons find and remove the exact lesion with confidence. Genetics, IVD, and Risk Personalization Innovation isn’t confined to imaging. In vitro diagnostic (IVD) technologies aimed at understanding a patient’s genetic profile allow the health care team to focus prevention and treatment choices: Access to genetic testing shapes real decisions—ranging from intensified screening to prophylactic surgery—illustrating how diagnostics influence the care pathway long before a device enters an operating room. Beyond BRCA1/2, expanded hereditary cancer panels are identifying additional gene variants linked to breast cancer risk. These insights allow patients and their families to consider enhanced surveillance or risk-reducing strategies earlier. AI for Treatment Planning and Shared Decisions Diagnosis is only the start; choosing a path forward can be overwhelming. Emerging AI-enabled decision support is helping synthesize each patient’s history (family risk, allergies, prior therapies) with diagnostic findings to propose tailored treatment regimens. The goal isn’t to replace clinicians, but to reduce cognitive load and present options that align with evidence and patient preferences—especially valuable in the intense, time-pressured period after diagnosis. Therapy Delivery: Precision, Protection, and Performance Treatment advances span devices, delivery systems, and protective technologies: Targeted systemic therapies (e.g., monoclonal antibodies) and immunotherapies are increasingly paired with smarter delivery. While these are pharmaceuticals, MedTech plays a pivotal role in making therapy more precise and accessible to patients. Radiation oncology continues to advance toward highly focused, image-guided targeting—concentrating dose where it is needed and sparing healthy tissue. Closed system transfer devices (CSTDs) exemplify overlooked but vital innovation. By preventing aerosolization and exposure during chemotherapy preparation/administration, CSTDs protect clinicians—often repeatedly exposed over years—while ensuring the dose reaches the patient safely. Keeping caregivers safe is part of high-quality cancer care. The Often-Unspoken Dimension: Mental Health Several speakers shared that the toughest period can come after active treatment, when uncertainty and anxiety can surge. Technology like telehealth access, symptom-tracking apps, and peer-support platform, can help, but it’s also a reminder that: Patient-reported outcomes and quality-of-life measures deserve equal attention in product design and post-market follow-up. Care pathways should anticipate the emotional arc of treatment and recovery, not just the clinical milestones. Weighing the benefits and risks of a diagnostic procedure or a treatment is a personal decision that can vary widely between patients and have long-term effects.  What Startups Can Learn (Regulatory View From Idea to Launch) RQM+ regulatory experts on the panel described working with startups from idea-stage concepts through to clearance and launch. Three enduring takeaways for innovators: Evidence first: Whether AI for screening or a new biopsy tool, plan your clinical and analytical validation early. Define endpoints that matter to patients and clinicians. Safety & effectiveness, then scale: Cybersecurity, usability, and human factors are non-negotiable for software and devices used in high-stress clinical contexts. Think ecosystem: Great solutions often live at the intersections—imaging + AI, device + drug (combination products), clinic + home monitoring. Build for interoperability and real-world use. Closing Thoughts on MedTech in Breast Cancer Treatment Breast cancer care is being reshaped by MedTech advances that see more, personalize earlier, treat more precisely, and protect everyone involved. AI-augmented imaging guides biopsies; genetic and IVD advances inform diagnosis and treatment; improved radiation delivery tools minimize collateral harm; CSTDs safeguard clinicians; and patient-centered communication plus mental-health awareness complement the experience. The throughline from the panel was clear: today’s innovations are profoundly improving lives—but only when paired with rigorous evidence and thoughtful implementation. For founders and teams building the next generation of solutions, keep patients at the center, design for the realities of care, and partner early on regulatory strategy. That’s how technology leads to better outcomes—and why many of us feel, as one panelist put it, lucky to be alive now to see what’s possible. In recognition of Breast Cancer Awareness Month, the World Health Organization continues to expand global access to education and resources focused on early detection, timely diagnosis, and comprehensive treatment. Explore their initiatives here to learn more about how awareness drives action and outcomes. Want to dive deeper? Watch the full RQM+ panel discussion on our YouTube channel. #### How Polymer Testing Helps Medical Device Manufacturers Prevent Material Failures In the medical device industry, material reliability is non-negotiable—polymer failure can compromise patient safety, regulatory compliance, and brand reputation. As medical technology advances, manufacturers increasingly rely on polymer-based materials for implantable devices, surgical tools, drug delivery systems, and wearables. Ensuring these materials meet stringent performance and safety standards is critical. Comprehensive polymer testing plays a pivotal role in identifying potential failure mechanisms, extending product longevity, and ensuring compliance with regulatory requirements such as ISO 10993 and FDA material guidelines. By proactively addressing material vulnerabilities, manufacturers can reduce risks, prevent device recalls, and enhance overall patient safety. Identifying Failure Mechanisms in Medical Devices Material failures in medical devices can have serious clinical consequences. Understanding and preventing these failures is essential to maintaining device integrity and patient safety. Some of the most common failure mechanisms include: 1. Mechanical Failures Medical devices experience repeated stress, strain, and load-bearing conditions. Common mechanical failure risks include: Fatigue and creep rupture in long-term implantable devices (e.g., orthopedic implants, cardiovascular stents) Brittle fractures in single-use polymer instruments under excessive force Abrasion and wear in catheter coatings or prosthetic joint materials Key Tests: Tensile testing, fatigue testing, impact resistance, and wear analysis. 2. Thermal Failures Sterilization methods like autoclaving, gamma irradiation, and ethylene oxide (EtO) exposure can degrade polymer structures during processing, affecting device safety and longevity. Processing steps also subject materials to thermal stresses. Thermal failures include: Material shrinkage or embrittlement during processing Depolymerization or softening in heat-sensitive components (e.g., drug delivery reservoirs) Molecular weight degradation due to excess heat or exposure to irradiation. Key Tests: Gel Permeation (Size Exclusion) Chromatography (GPC), Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and accelerated aging studies. 3. Chemical & Biocompatibility Failures Polymers used in medical applications must withstand bodily fluids, cleaning agents, and pharmaceutical interactions without degrading. Common risks include: Oxidation and hydrolysis, leading to polymer breakdown in implantable devices Leaching of toxic substances, impacting biocompatibility and FDA compliance Stress corrosion cracking (SCC) from prolonged exposure to disinfectants or drugs Key Tests: Chemical resistance testing, Antioxidant content determination (LCMS, GCMS), extractables and leachables analysis, and biocompatibility assessments (ISO 10993). Enhancing Product Quality & Regulatory Compliance Stringent polymer testing not only reduces device failures but also streamlines regulatory approval. Key benefits include: Identifying possible material problems prior to time consuming biocompatibility testing. Ensuring Batch-to-Batch Consistency: Tight quality control ensures that polymer properties remain consistent across multiple production runs. Meeting FDA & ISO Standards: Thorough testing supports compliance with ISO 10993 (biocompatibility), ISO 11607 (sterile packaging), and FDA 21 CFR Part 820 (quality systems regulation). Tailoring Polymer Testing for Medical Applications Medical devices require customized polymer testing strategies that reflect real-world usage and worst-case scenarios. A robust testing approach should include: Multi-Faceted Testing: Combining mechanical, thermal, and chemical analyses for a comprehensive assessment. Application-Specific Protocols: For example, implantable devices need extensive biocompatibility and degradation testing, while single-use surgical tools require precise mechanical strength evaluations. Continuous Innovation: Staying updated with the latest material science advancements and regulatory expectations ensures optimal testing outcomes. Closing Thoughts For medical device manufacturers, polymer testing is more than just quality control—it’s a critical safeguard for patient safety and regulatory compliance. By identifying failure risks early, optimizing material selection, and ensuring long-term stability, companies can create safer, more reliable, and longer-lasting medical devices. A proactive approach to polymer testing not only enhances product performance but also strengthens brand trust and regulatory approval pathways.If you’d like to learn more about the RQM+ approach to polymer testing, contact a member of the team today. For more on a related topic - Latex and DEHP and BPA, Oh my! or Embracing Recalls or How to Choose a GPC Column or Polymer Failure Analysis with Jordi Labs, an RQM+ Company #### How to Choose a GPC Column Gel Permeation Chromatography (GPC) is a powerful technique that provides a direct measurement of molecular weight, a critical property in characterizing natural and synthetic polymers. There is no universal GPC system with the capability to separate every polymer-based exclusively on size, so how do you choose the correct column tailored specifically for your sample? Choosing a Mobile Phase It all starts with the mobile phase. What is your sample polymer soluble in? A polymer that is insoluble cannot be analyzed by GPC, making solvent selection paramount. For an efficient GPC separation based only on size, the optimal solvent should be strong enough to minimize the sample-column interaction. Don’t Sacrifice on Resolution When choosing GPC columns, it is essential to decide on the level of resolution desired for your samples and standards. Remember the golden rule: resolution and separation efficiency increases directly with the column’s volume (pore volume). The length and internal diameter (ID) of each column should be carefully considered prior to purchasing any column set. We would suggest: Using a longer column, or multiple columns in series (two 30 cm in series vs. one 30 cm column)¹ Choosing a column with a larger internal diameter (22 mm vs. 7.8 mm) An advantageous solution to poor resolution is to include an additional column in series to your current system. “Free resolution” can be obtained by increasing the column temperature or by choosing the optimal injection volume/concentration for your system. Pore Size Matters GPC utilizes a non-interactive stationary phase, composed of a porous network, allowing for an elution order based on decreasing molecular size.  There are a number of pore sizes available, and each pore size excels at separating a specific molecular weight range (Table 1).The Mixed Bed column is a linear column, and is strongly recommended for routine or unknown sample analyses. The column pore size should be chosen based on the suspected molecular weight range of the polymer being analyzed. “It’s Just a Phase…” Let’s summarize what we know now: the chromatographic eluent based on sample solubility, the number of columns and dimensions based on resolution desired, and the pore size based on the suspected MW range of the sample Would you like to learn more? Contact a member of the RQM+ Lab Services team today with any questions about gel permeation chromatography, or selecting a GPC column. ¹This would result in a 2 fold increase in pore volume, based on an increase in column length. Related Techniques Gel Permeation Chromatography #### How to Choose the Best Fit PMCF Strategy: Full-Scale PMCF Trial vs. PMCF Survey Post-market clinical follow-up (PMCF) is a central requirement under the EU Medical Device Regulation (MDR). Its purpose is to confirm the safety and performance of medical devices once they are on the market and used in real-world conditions. For medical device manufacturers, choosing the right PMCF strategy can be challenging, and potentially costly. Two of the most common approaches are full-scale PMCF clinical trials and PMCF surveys. Each carries its own strengths, limitations, and ideal use cases. This article explores both strategies, offering guidance on when to choose one over the other. What are the Strategies for PMCF? Manufacturers have several PMCF strategies available, and the choice depends on the device type, risk classification, and the amount of existing clinical evidence already supporting the device. The EU MDR emphasizes that PMCF is not optional but an integral part of the post-market surveillance (PMS) system. At minimum, manufacturers are required to plan and conduct reactive general PMCF activities such as complaint monitoring, review of public vigilance databases for adverse events and field safety notices, and periodically review the scientific literature. Where there are gaps or an absence of high quality evidence to demonstrate safety and performance for all intended uses for all indications and patient populations, if there are significant changes to the design or indications, or if initial certification was based on regulatory strategies such as equivalence, specific PMCF activities may be required. The two most widely recognized proactive specific PMCF methods are: Full-Scale PMCF Clinical Trials: These are prospective, interventional or non-interventional studies designed to collect high-quality, real-world clinical data. Unlike pre-market clinical investigations, PMCF trials are conducted in routine clinical practice and may include larger, more diverse patient populations. They are particularly important for implantable devices, high-risk Class III devices, and novel technologies where long-term performance and safety outcomes must be confirmed. PMCF Surveys: Structured questionnaires distributed to healthcare professionals (HCPs) and/or patients. These can be retrospective chart reviews where clinical data is reported directly from patient records, or can solicit general experience feedback such as usability, satisfaction, or perceived performance. Data is collected through non-interventional efforts, collects real-world evidence, and typically does not have the same requirements as clinical trials - most notably not requiring adherence to ISO 14155 or ethics committee / institutional review board (IRB) approval. Surveys can also help detect emerging safety signals or usability issues across different regions, clinical settings, and user groups. In addition to these core approaches, other specific PMCF activities may include: Device Registries: Longitudinal databases tracking outcomes for specific devices (commonly used in devices like joint replacements, cardiovascular stents). Analysis of Real-World Evidence (RWE) from other sources such as insurance claims databases. While all these activities may be acceptable PMCF methods under MDR, PMCF clinical trials and surveys remain the most common pathways for closing gaps in evidence, ensuring continued device safety and performance, and demonstrating ongoing compliance when general methods alone are not sufficient. When to Choose a Full-Scale PMCF Trial? A full-scale PMCF clinical trial is often the preferred option when: Device Risk is High: Class III or implantable devices usually demand rigorous post-market data. Limited Pre-Market Evidence Exists: New technologies or novel mechanisms of action require additional validation beyond initial clinical investigations. Specific Safety Concerns Arise: If signals of risk appear during post-market surveillance, a trial can help confirm or rule out potential hazards. Endpoints Must Be Objectively Measured: Some quantitative performance data, complication rates, or device lifetime claims are better assessed through structured clinical trials. There are significant changes to design or indications: Use of devices outside approved use or with significant changes in patients likely requires adherence to standards for clinical investigations such as ISO 14155 While these trials provide the strongest level of evidence, they are resource-intensive. Manufacturers must weigh regulatory expectations against costs and time to complete them. When to Choose a PMCF Survey? A PMCF survey may be more appropriate in scenarios where: The Device Has a Well-Established Safety and Performance Profile: Mature technologies with a long history of real world usage, but there are gaps in reported evidence. Wider Clinical Experience Needs to Be Captured: Surveys can cover diverse user groups, geographies, and clinical settings efficiently. Quantitative Data is Needed: Retrospective chart review studies can quickly gather high-quality clinical data for approved devices used according to labeling. Qualitative Insights Are Valuable: Information about usability, ease of use, user satisfaction, and perceived safety and performance is often best gathered through direct feedback and can be gathered quickly from existing users. Resource Constraints Exist: Compared to full-scale trials, surveys are less expensive, quicker to implement, and easier to repeat periodically. Lifetime Claims have Gaps: Implants can be approved without long-term data, but PMCF data at mid- and long-term follow-up is expected to substantiate lifetime claims That said, surveys must be carefully designed to avoid bias, ensure representative responses, and provide enough depth to satisfy regulators. Key Considerations for Both Strategies Full-Scale PMCF TrialPMCF SurveyLevel of evidence (per MDCG 2020-6 Appendix III)High (Rank 1 or 2)Moderate – low (Rank 4 or 8)Best forHigh-risk devices (Class III), novel technology, major clinical data gaps, long-term performance issuesLower-risk or well-established devices, usability feedback, general user experience, supplementing other evidenceProsHighest data quality, maximum regulatory acceptance, systematic and controlled data collectionCost-effective, time-efficient, adaptable, can reach a large user baseConsHigh cost, resource-intensive, long timelines, complex regulatory processLower evidence quality, potential for bias, depends on user access and response rates Partner with RQM+ for Your PMCF Strategy Navigating the complexities of EU MDR compliance requires more than a checkbox approach. A well-structured PMCF strategy not only meets regulatory requirements but also safeguards patients and supports the long-term success of your device portfolio. At RQM+, we bring together deep regulatory acumen, clinical expertise, and cross-functional execution to help you design and implement PMCF activities that stand up to notified body scrutiny. Whether your needs call for a full-scale clinical trial, targeted surveys, registry participation, or literature reviews, our specialists build strategies tailored to your device’s risk class, evidence gaps, and life cycle stage. Why Work with RQM+? Strategic Alignment: We develop actionable PMCF plans and reports that align with MDR and IVDR requirements, ensuring your activities are defensible and future-proof. Integrated Support: Our regulatory, clinical, quality, and testing experts collaborate seamlessly with your team, scaling from advisory input to full outsourcing depending on your internal resources. Regulatory Insight: With constant updates to EU MDR expectations, we keep you ahead by interpreting notified body feedback and guiding multi-year PMCF planning. Operational Efficiency: By managing complex PMCF activities, we reduce the risk of regulatory delays and free your team to focus on innovation and commercialization. Building Your PMCF Roadmap Whether you are addressing legacy device compliance, preparing for new product launches, or optimizing existing PMCF studies, RQM+ can help you move forward with confidence. Our approach combines scientific rigor with practical execution, giving you the assurance that your devices continue to perform safely in the real world. Connect with us today to discuss how RQM+ can strengthen your PMCF strategy and support your broader regulatory and clinical goals. In case you missed it, here's your chance to dig deeper into the nuances of PMCF survey success with our expert panel. Watch the on-demand discussion, PMCF Surveys That Survive Scrutiny, to gain practical insights on designing, executing, and defending surveys that meet MDR expectations. For more, read - Ten Tips for A Successful Use of Total Product Life Cycle (TPLC) Reports #### How to Develop a Biological Evaluation Plan A biological evaluation plan is developed to systematically assess whether a device intended for use in humans poses an unacceptable biological safety risk. The Food and Drug Administration (FDA) Guidance document, Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” (2020), sets out information on the general principles of biological evaluation of medical devices within a risk management framework.1 Areas to be considered in a biological evaluation plan include the intended use of the device, its materials of construction and manufacturing process, available biological safety data, and knowledge gaps which should be addressed through testing. Testing used to support the biological evaluation process may include chemical characterization and toxicological risk assessment, cytotoxicity, irritation, sensitization, hemocompatibility, pyrogenicity, genotoxicity, and systemic toxicity. A robust biological evaluation plan is not just important from a safety perspective, but can also help to improve efficiency in device testing and development. RQM+ Lab Services is an expert in the biological evaluation of medical devices and biocompatibility testing and can help you understand what tests are required as part of a biological evaluation plan, so you do not waste any time on unnecessary testing. Creating a Biological Evaluation Plan  A biological evaluation plan must be created with the support of ‘knowledgeable and experienced professionals’ as established in ISO 10993-1.1 This is why involving a partner like RQM+ Lab Services can help accelerate and improve your biological evaluation processes. The first part of creating a biological evaluation plan is to consider what biological evaluation information is available and missing for any materials that would be used, in the context of the finished device. It is acceptable in biological evaluation to make use of existing data on biological risks if the previous biological evaluation and testing has been carried out under sufficiently stringent conditions and is representative of the finished device configuration. This is one way a thorough review before starting any biological evaluation can help avoid any unnecessary testing. It is also important to consider, particularly for new materials that have no prior usage in medical devices, whether the properties of the isolated material and medical device may be different. A biological evaluation must evaluate the risk of all relevant biological safety endpoints prescribed by ISO 10993-1:2018 for the specific device category. This includes consideration of the duration and type of contact with the body. Systemic endpoints, such as genotoxicity, carcinogenicity, and acute or chronic systemic toxicity, may be addressed through either biological testing data or chemical characterization and toxicological risk assessment data. On the other hand, localized endpoints, such as cytotoxicity, irritation, and hemocompatibility, generally require biological testing data. RQM+ Lab Services can help you evaluate what steps you need to include in your biological evaluation process and how to remain compliant with any biological evaluation legislation and regulations. RQM+ Lab Services also has 40 years of experience in chemical testing, so for new materials that require extensive testing and characterization, the company can bring that expertise to your biological evaluation process. References ISO 10993-1:2018, https://www.iso.org/standard/68936.html, accessed April 2022 FDA Guidance Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” (2020) #### How to Navigate SaMD Regulatory Pathways: From FDA to EU MDR & IMDRF Software as a Medical Device (SaMD) refers to software intended for medical purposes that functions independently of any hardware device, differing from SiMD which is the essential firmware embedded into a physical device. For MedTech startups, navigating SaMD regulatory pathways is one of the most complex yet critical aspects of product development. The challenge lies not only in meeting local regulatory expectations, such as the U.S. Food and Drug Administration (FDA) requirements or the European Union’s Medical Device Regulation (EU MDR), but also in aligning with international frameworks like the International Medical Device Regulators Forum (IMDRF). Achieving compliance across these jurisdictions ensures patient safety, market access, and investor confidence. In the fast-growing digital health sector, innovation must go hand in hand with regulatory discipline. Understanding SaMD and Global Frameworks The IMDRF defines SaMD as software intended for one or more medical purposes that performs these purposes without being part of a hardware medical device. This definition established a foundation for global harmonization, enabling regulators across regions to interpret and categorize software consistently. IMDRF’s SaMD framework outlines three key principles: Risk-based categorization: SaMD is classified based on its intended purpose and the significance of the information it provides to healthcare decisions. Clinical evaluation: Developers must demonstrate analytical validity, clinical validity, and clinical performance. Life cycle management: SaMD requires continuous evaluation and control throughout its life cycle, from design to post-market monitoring. Many regulators, including the FDA, EU, and Japan’s PMDA, have adopted these IMDRF principles. Aligning early with IMDRF guidance can streamline multi-region approvals and reduce rework later in development. FDA’s SaMD Regulatory Pathway (U.S.) In the United States, SaMD products are regulated as medical devices under the FDA’s risk-based framework. SaMD classifications span Class I—III, depending on the level of risk to patients. The main pathways for U.S. market entry include: 510(k) clearance for moderate-risk devices demonstrating substantial equivalence to a predicate. De Novo classification for novel devices with low to moderate risk where no predicate exists. Premarket Approval (PMA) for high-risk, novel applications that require substantial clinical evidence. FDA guidances such as “SaMD: Clinical Evaluation” and its risk categorization framework are built directly on IMDRF principles. The Digital Health Center of Excellence leads ongoing initiatives, including guidance for AI/ML-based software and cybersecurity expectations. Submissions typically require strong evidence of safety, effectiveness, and cybersecurity management. Additionally, the FDA applies enforcement discretion to certain low-risk health and wellness applications, reducing the regulatory burden for developers of software with minimal patient impact. Predetermined Change Control Plans (PCCPs) and evolving Notified Body (NB) scrutiny are timely aspects of this trend. Naturally, there are differentiating clinical expectations between different regulatory bodies. For example, the FDA requires clinical data only when risk of claims require it, whereas the EU’s Medical Device Regulations (MDR) demand a CER, and often Post-Market Clinical Follow-up (PMCF) for every SaMD. EU MDR Compliance for SaMD (Europe) The EU’s Medical Device Regulation (MDR 2017/745) has significantly raised the bar for software compliance in Europe. Under Rule 11, most standalone diagnostic or therapeutic software now falls into Class IIa, IIb, or III, depending on its intended use and potential risk. This reclassification means that self-certification, once common under the old MDD, is now rare. Key steps for achieving MDR compliance include: Determine qualification and classification: Verify the software’s medical purpose and apply Rule 11 to establish its risk class. Prepare Technical Documentation: Include clinical evaluation, risk management (ISO 14971), cybersecurity measures, and usability evidence (IEC 62366). Conformity assessment: Work with a Notified Body for review and certification (mandatory for Class IIa and above). Post-Market Surveillance (PMS): Implement systems for continuous monitoring, software updates, and vigilance reporting (e.g., PMCF studies). Recent EU developments, such as extended transition timelines for legacy devices, do not apply to new SaMD as these must meet MDR requirements immediately. IMDRF and Other International Pathways Beyond the U.S. and EU, many countries align their SaMD frameworks with IMDRF principles. For example: Canada and Australia follow risk-based approaches similar to IMDRF. Japan’s PMDA uses a tiered structure for approval and post-market control. China’s NMPA has adopted IMDRF-aligned definitions, though its approval processes remain distinct. Maintaining global consistency through IMDRF-aligned categorization allows companies to develop a unified regulatory strategy. As IMDRF continues to refine its guidance, especially for AI and adaptive algorithms, staying informed is crucial for long-term compliance planning. Practical Tips for Navigating Multiple Pathways Navigating multiple regulatory systems requires strategic foresight and cross-functional collaboration. MedTech startups can reduce friction by: Designing for dual compliance: Build documentation and evidence that satisfy both FDA and MDR requirements simultaneously. Starting classification early: Early engagement with regulators or consultants helps prevent misclassification, one of the most common and costly mistakes. Implementing a robust QMS: Adhere to ISO 13485 for quality systems and IEC 62304 for software lifecycle management. Maintaining traceability: Ensure that all requirements are linked from design to testing and risk management. Partnering with experts: Organizations like RQM+ specialize in guiding SaMD developers through the nuances of both FDA and EU MDR processes, helping to align regulatory and business strategies for efficient market entry. Engage with regulations early: FDA Q-Submissions and early Notified Body interactions can prevent misclassification and rework. Conclusion and Future Outlook Successfully navigating SaMD regulatory pathways requires an early, integrated approach that embeds compliance into product development. Companies that leverage IMDRF’s risk framework, conduct thorough clinical and cybersecurity evaluations, and plan proactively for post-market obligations position themselves for success across global markets. The regulatory landscape for digital health is dynamic as emerging AI/ML regulations and real-world evidence requirements are reshaping expectations. For innovators, agility and regulatory literacy are as vital as technical excellence. Aligning innovation with compliance not only accelerates approvals but also builds trust with clinicians, investors, and patients. With informed strategy and the right partnerships, MedTech startups can turn regulatory complexity into a competitive advantage. If you need expert guidance navigating SaMD regulatory pathways or aligning your digital health innovation with global requirements, contact us to partner with specialists who live and breathe MedTech compliance. #### How to Obtain CE Marking Under the IVDR CE marking is the system used in the EU to indicate that products meet the region’s safety, health, and environmental protection requirements. Products labeled with the CE marking can be freely traded in the European Economic Area without restrictions. Requirements for obtaining CE marking vary depending on the type of product. For in vitro diagnostic devices (IVDs), manufacturers are currently subject to the European Directive 98/79/EC (IVDD), but new legislation will put the In Vitro Diagnostic Regulation (IVDR) into effect in May 2022.   The EU Commission gave manufacturers five years to comply with the new IVDR CE marking requirements because it represents such a seismic shift in the way IVDs are regulated. With the deadline fast approaching and a limited number of certified notified bodies, many people are banking on an extension that may or may not be forthcoming. The first step is to gain an understanding of the new requirements for obtaining CE marking for IVDs. Changes in CE Marking Requirements from IVDD to IVDR Currently, under the IVDD, only 10-20 percent of IVDs require notified body involvement while the rest are allowed to self-certify. The IVDR regulation flips these numbers so that 80-90 percent will require notified body involvement.  A significant hurdle for manufacturers is the increase in requirements for IVDR as compared to IVDD and the stringency that notified bodies are using in enforcement. With little more than a year before the deadline, it’s important to start assembling the performance data and supporting clinical evidence required in the IVDR technical documentation so that you have time to identify and remediate the gaps. Notified bodies are taking several months to review files, often with multiple rounds of questions, so this also needs to be accounted for in your timeline.  One of the most significant changes with the new IVDR is the move from a list-based classification system to a rule-based one. Classifications will be largely based on the intended purpose of the device, and the definition of medical devices extends to all technologies, including software. All IVDs are subject to reclassification, and there is no one-to-one relationship between the existing classification and the new one.  Notified bodies will also be reviewing technical documentation for significantly more products than under the IVDD. All Class D, Class C companion diagnostics, self-testing devices, and point-of-care devices will have all technical documentation evaluated. For other classifications, notified bodies will use a random sampling by device group to assess the overall state of compliance. The manufacturer doesn’t have the option to choose which files are presented, and all files will be ultimately reviewed over a rolling five-year period. We’re seeing it take about three months to get through the initial application process with the notified body to establish a contract and then an additional year or more to complete the review and approval process for medical device reviews under the EU MDR. We expect the review times to be similar for IVDR. Our former notified body representatives advise that there could be an opportunity to get a faster review if you are one of the first to apply because the reviewers aren’t bogged down yet. Use our IVDR Readiness Assessment to determine what steps you need to take to be ready for the upcoming IVDR deadline. IVD companies are known to have deficient risk management files because they are often created by suppliers and have rarely been reviewed by notified bodies. This will not be the case going forward, and achieving ISO 14971 compliance will be challenging. Under the IVDR, clinical performance can be demonstrated through studies, peer-reviewed published literature, and experience gained through routine testing. For performance evaluation reports (PERs), which must be updated on an ongoing basis and support the clinical benefit and clinical utility of the IVD test, regulators will be looking at analytical and clinical performance and scientific validity with a high level of scrutiny. For Class C and D devices, the PER must be updated at least annually, and Class A and B devices must be updated as needed.  It is worth noting that if your device is 510(k) cleared in the U.S., you will have already obtained much (but not all) of the testing and performance data required under the new IVDR. This data would not be compiled into the PER format required by the IVDR.  However, if your device is 510(k) exempt, you may be more likely to have gaps in your evidence to IVDR. Devices that contain hazardous substances and were previously exempt face new restrictions and labeling requirements. Many manufacturers are having a hard time obtaining the level of detail needed from suppliers for compliance, which is yet another reason to start the process sooner than later. An additional challenge is that the IVDR is more restrictive regarding what hospital labs can do on their own, forcing manufacturers to source new providers, potentially causing further delays. Requirements for Obtaining CE Marking Under IVDR All IVDs marketed in the EU must have CE marking under the IVDR by May 2022. To obtain CE marking for a new product or currently marketed product under IVDD, the approval process requires full compliance with the IVDR, including: Determining product classification Updating your quality management system (QMS) for IVDR compliance and conducting training and an internal audit Obtaining notified body audit and certification of QMS  Appointing a person responsible for regulatory compliance (PRRC)  Preparing suppliers for unannounced notified body audits Preparing the technical documentation file, which includes: Device specification, including the intended purpose/use, principles of method/operation, and so on An overview of previous and similar generations of the device General safety and performance requirements and supporting evidence Risk/benefit analysis Risk management file and risk/benefit analysis (ISO 14971:2019 compliance) Verification and validation testing reports  Performance evaluation plan and report (PEP/PER) Post-market surveillance plan (PMS)  Post-market performance follow-up plan (PMPF)   Updated labeling, including instructions for use and translations Manufacturing information  Declaration of conformity Obtaining technical documentation audit and certification by the notified body  (certificate that provides approval for CE marking) Appointing a European Authorized Representative (if you have no physical location in Europe) with the required liability insurance to hold copies of your technical documentation (No change from IDD) Identifying economic operators within your supply chain Obtaining a unique device identifier (UDI) Obtaining certification from the notified body, which is approval to affix your CE marking Affixing your CE marking to product labels Registering the authorized representative and importer with the EUDAMED database when it goes live After the initial submission and approval, manufacturers will be routinely audited by notified bodies to make sure products are still eligible for IVDR CE marking. Although the EUDAMED database is not yet fully live, the actor module that allows you to obtain a single registration number (SRN) is active, so you can add your devices now. If you currently have IVDs on the market with CE marking under IVDD, there will be no “grandfathering” that will allow you to continue marketing those products after the IVDR deadline. All IVDs must go through the process to obtain a new CE marking that conforms to the IVDR requirements. RQM+ Is Here to Help Obtaining CE marking under the IVDR clearly requires a significant effort and dedicated resources, especially for manufacturers with devices that were previously self-certified. Fortunately, the RQM+ team is here to help you every step of the way, whether you just need a little help compiling your technical documentation or want us to guide you through the entire process. Use our IVDR Readiness Assessment to determine what steps you need to take to be ready for the upcoming IVDR deadline. How to Obtain CE Marking Under the MDR #### How to Obtain CE Marking Under the MDR In the EU, CE marking is the system used to demonstrate that products meet the region’s requirements for safety, health, and environmental protection. When a product is labeled with the CE marking, it can be freely traded in the European Economic Area (EEA) without restrictions.  Different types of products have different requirements for obtaining CE marking. For medical devices, manufacturers with new and re-certifying products are subject to Regulation (EU) 2017/745, also known as the EU Medical Device Regulation, or MDR. For manufacturers that are new to CE marking under the MDR, the first step is to gain an understanding of the requirements for obtaining CE marking for medical devices. MDR CE Marking Process Because obtaining a CE marking for a medical device allows it to be freely traded in the EEA, the process for ensuring it meets the requirements for patient safety is rigorous. This is a brief overview of the steps you can expect to take when securing a CE marking for your device. Classify your device  Under MDR, a medical device is classified according to its risk profile following the 22 classification rules in Annex 8. The classification does not follow a decision tree and does not depend on finding predicate devices, as in some other markets. Instead, classifications are primarily based on the device’s intended purpose. It’s also important to know that the definition of medical devices extends to all technologies, including software. This is a critical first step because the device classification informs the regulatory requirements and approval path you must follow. Designate a person responsible for compliance (PRRC) All manufacturers that market medical devices in the EU must designate a PRRC, as defined by Article 15 in MDR. The role of this employee is to ensure that the product conforms with quality system management, technical documentation is maintained, post-market surveillance obligations are met, and reports are prepared as required. The designated employee must have regulatory experience, which is defined as either formal qualification in a relevant scientific discipline with at least one year of relevant experience with medical devices, or four years of relevant medical device experience. In the case of the PRRC, the relevant experience must be with quality management systems or regulatory affairs for medical devices. Implement a quality management system In order to obtain a CE marking, medical device manufacturers and critical suppliers must comply with EN ISO 13485, which is the quality management standard accepted by notified bodies under MDR. To stay in compliance, certification must be renewed every year. Prepare suppliers for audits Suppliers must be prepared for unannounced notified body audits to ensure that they are in compliance with MDR. Prepare your suppliers by performing mock audits to identify and address weaknesses. Prepare technical documentation MDR Annex I, II, and III require technical documentation to include: Device specification, including the intended purpose/use and principles of method/operation An overview of previous and similar generations of the device General safety and performance requirements (GSPR) and supporting evidence Risk/benefit analysis Risk management file and risk/benefit analysis (ISO 14971:2019 compliance) Verification and validation testing reports  Clinical evaluation plan and report (CEP/CER) Post-market surveillance plan (PMS)  Post-market clinical follow-up plan (PMCF)   Updated labeling, including instructions for use and translations Manufacturing information  Declaration of conformity The technical file must also meet certain administrative requirements, so it is important to ensure you meet those before submitting to the notified body or it could result in a delay. Appoint an authorized representative For manufacturers that are not established in the EU, an authorized representative is required to obtain CE marking. Also known as an EC REP, this entity must be located in the EU and acts as the main point of contact between the manufacturer, notified body, and national competent authorities. Contact information for your authorized representative must be displayed on your labeling, IFU, or outer packaging. You must also obtain a single registration number for use by the manufacturer, authorized representative, and importer. Submit to notified body review Your technical documentation and quality management system must be audited by a notified body. This process includes a review of the technical file and up to three rounds of questions. Because each round of questions requires an investment of resources, the better you are prepared with the first submission, the faster and more cost-effective the process will be. When approved, you will receive a European CE Marking Certificate for your device that is good for up to five years and you can: Prepare a declaration of conformity Affix your CE marking Register your device and unique device identifier (UDI) in EUDAMED Maintain your CE marking Maintaining your CE marking requires submitting to routine notified body audits and keeping your technical documentation in compliance. You must also perform clinical evaluation, post-market surveillance (PMS), and post-market clinical follow-up (PMCF) activities to maintain certification. Challenges with CE Marking Under MDR Manufacturers that are familiar with CE marking under MDD may face some challenges staying compliant under MDR. For example, more stringent post-market surveillance requirements necessitate integrating data from multiple systems, including PMS, PMCF, and risk management. Maintaining compliance also means implementing systems to keep technical documentation updated so files are always audit-ready. Manufacturers with multiple product lines might also find it difficult to prioritize submissions based on factors such as revenue, product life cycle, the time required for submissions, and business goals.   How RQM+ Helps RQM+ has developed finely honed best practices for compiling technical documentation that will pass notified body review with minimal questions. We have experts in every area—clinical, regulatory, quality, and risk management—and experience across all device classes. We also have former notified body leadership on staff so we are uniquely positioned to meet reviewer expectations. If you have multiple product lines and are not sure where to focus your efforts first, RQM+ provides risk-balanced solutions for portfolio planning based on your business objectives. Once the best path forward has been identified, our team of expert implementers can handle initial submissions and maintenance so you can focus on new product development and other priorities. If you would like to learn more about our CE marking services for medical devices and how we can add value to your business, contact us today to schedule a consultation. #### How to Prepare a Design History File for FDA Inspection Food and Drug Administration (FDA) inspections are stressful, especially if your documentation isn’t audit-ready. Creating and maintaining a compliant design history file (DHF) will help ensure that when the time comes, you’ll be ready for an FDA inspection that results in minimal findings. It’s not uncommon for DHFs to be lacking, especially when the product development process doesn’t have a strong emphasis on regulatory requirements. Device designers are focused on what they do best, not necessarily prioritizing documenting design controls along the way. The more proactive you can be, the fewer issues will arise. Don’t wait until a surprise inspection to learn that your DHF needs some work. Elements for Inclusion in Your Design History File A DHF is the complete record of the design and development of a device—“complete” is the keyword here. The FDA is looking for the DHF to, “contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part." The FDA will look at your design controls procedure and ensure it includes the following elements: Design and development plan Design input Design output Design review Design verification Design validation, with software validation if applicable Design transfer Design changes In addition to these components, including a description of the file with the product it pertains to, the documents that are included in the file, and the complete history of the design. Include all relevant elements such as: Device development Accessories Major components Labeling Packaging Manufacturing process Because the DHF is the collection of this documentation showing the evolution of the design, it must be assembled and updated properly because it will be referenced throughout the life of the product. When maintaining a DHF, medical device companies must assess it for changes even beyond the development phase to ensure it accurately represents the product being delivered. Activities and Deliverables by Design Controls Stage Concept development There are no specific deliverables at this stage, but any animal or clinical studies should be documented in case they are included in a future 510(k). Develop and document a clinical trial strategy if needed for verification and validation testing. The risk management team should research complaints about similar devices and identify any initial hazards that could influence the design process. At this stage, a pre-IDE meeting with the FDA is also encouraged.  Design and development planning Design control activities officially begin at this stage. Create a design and development plan that describes all of the activities that will be completed as part of design controls and that demonstrates that adequate resources and time will be committed to these activities to ensure the development of a safe and effective product. Periodically update the plan throughout product development. It should tell the story of the product’s development, from design input through transfer to manufacturing. In an FDA audit, the plan is typically one of the first documents to be requested and provides the auditor with a road map of design and testing. Solidify marketing requirements and other inputs, including user needs which will link to formal product requirements.  And keep in mind that every design change requires a plan, and design change plans are often reviewed in FDA inspections. Design input Design input includes development and formal documentation of product requirements and system architecture design and software development planning. Consider using a design trace matrix that will eventually connect user needs with design inputs and outputs, verification, and validation references. Document product requirements and have them formally reviewed and approved by a cross‐functional team. Establish a solid set of requirements before proceeding to a detailed design. The design input set should be complete, unambiguous, not in conflict, and able to be verified or validated. Safety risk management per ISO14971 begins in this phase with a safety risk management plan and initial identification of patient or user harm that could result from proper use and foreseeable potential misuse of the product/system. Control of any significant risks should be included as design inputs. Begin documentation of the human factors plan and associated activities, including the definition of device user profiles (patient, family member, nurse, technologist, or physician), use environment, typical and atypical device use, and usability objectives. Design output At this stage, product requirements are translated into detailed design specifications, drawings, code, labeling, and so on, with the final design output being the product itself. This also includes software requirements specification, software design specifications, design and code reviews, detailed hazard analysis, and the verification and validation plan. The verification plan identifies the required tests and analysis, a preliminary trace to requirements, resources needed, the timeline, and risk areas or concerns. The validation plan identifies the methods to ensure that user needs have been adequately satisfied and should be done with a product representative of the final configuration/system. Verification and validation testing The stage includes the development and review of individual test protocols, verification of product requirements, and safety risk management controls. Reports are documented and include details of deviations and software anomalies. Deliverables at this stage also include the validation of manufacturing equipment and software. Design transfer The design history file for the product is complete and the design is transferred to manufacturing. The device master record (DMR)—the comprehensive recipe for manufacturing the product and includes drawings, software, procedures, work instructions, test plans, and so forth—must be complete before the start of production. Post-market surveillance At this stage, you must document and analyze customer complaints and reported product failures. Conduct design changes to correct issues and follow a design change procedure including, if necessary, design and development planning through to design transfer and any regulatory compliance steps. Best Practices for Preparing a Design History File By following a few best practices, you can help ensure that your DHF is always audit-ready.  Use FDA resources Review the FDA’s Guide to Inspections of Quality Systems to learn what the agency is specifically looking for in terms of management, design, production and process controls, and corrective and preventive actions (CAPAs). Look in the design controls section for guidance on DHF, which identifies 15 steps for verifying compliance with design control requirements in 21 CFR 820. Perform a gap analysis for every product  FDA can choose any DHF to review, so all of them should always be audit-ready. A gap analysis should be performed by a party that understands the device, design controls, and what regulators look for. Go digital If you currently use a paper-based process, consider upgrading to a digital system that enables easier tracking and updating. Inspectors will appreciate the ease of use and better organization. Start early and be consistent Don’t wait until late in the design process to create your DHF. Start it in predesign and follow quality system regulation (QSR) design controls. This saves time on document remediation and is more efficient than retroactively creating the file. Being consistent and adding documents as development occurs also ensures that your DHF is more complete and accurate. Gather input from production, regulatory, and quality functions early for a smoother transition to final production release. Document as much as possible More information is better, so be sure to include: Initial sketches Reasoning for material selection Prototypes Testing protocols Failures Bench testing and other preclinical work Validation and verification activities Design changes Plan your timeline When the project schedule is tight due to overruns along the way, there is a tendency to compact the verification and validation schedule at the end of the development process. Consider this in the planning stage and have contingencies for overruns built-in. Remember the business benefits Rather than viewing DHF creation and maintenance as a regulatory chore, think of the benefits it offers your business. Having a thorough and complete DHF provides a long-term memory for future designers to reference and the reasoning behind decisions in the design process. Failure studies also help avoid future mistakes and can be referenced in the event of issues with the device. Consider participating in MDSAP The Medical Device Single Audit Program (MDSAP) provides a prescriptive process that is easy to follow and a predictable audit schedule so you can always be prepared. The audit time is also predictable and based on the scope of your quality management system. One of the primary benefits of having MDSAP certification is that it allows you to forgo other FDA inspections, except for cause. How RQM+ Helps with DHFs RQM+ has subject matter experts, former regulators, and medical device auditors on staff, so we know what FDA looks for in a design history file. We provide business-balanced strategies that consider your goals and expert implementation to keep you in compliance. We also have experienced design quality engineers who understand your devices and can actively participate in new product development teams. If you would like help remediating a design history file or starting one early in the development process, contact us to schedule a consultation. For more on this topic - FDA Inspections Database #### How to Submit FDA CDRH Submissions Online As part of FDA Center for Devices and Radiological Health's (CDRH) Digital Transformation Initiative, several new tools have been released to strengthen the regulatory submission process. One of these tools is the Customer Collaboration Portal (CCP), which allows users to track the progress of their 510(k) submission. On 19 July 2022, FDA rolled out a new CCP feature allowing CDRH-led premarket submissions to be submitted online, which we are extremely excited about! At the time of FDA’s email, this feature is only available to current users of CCP. FDA continues to refine it prior to a full public release. We have known that this feature has been a long-time coming and have been anxiously awaiting its release, so we had to be one of the first to try it! The day after the feature was released, we submitted an eSTAR 510(k) through the new online portal. The process was extremely easy, intuitive and straightforward. You first start by logging into the CCP and selecting “Send a submission”. From there, you are given the option to submit an eSTAR or an eCopy of the submission. After selecting the format type, you can then select the file to upload. When the file is uploaded, all you need to do is press send. We submitted the submission on 20 July 2022 at 1:05 p.m. EST and received the FDA Acknowledgement Letter just three hours later (20 July 2022 at 4:07 p.m. EST)! This new feature is a game-changer and may be one of the best tools FDA has released. Gone are the days of having to find a USB/CD and physically going to a mailing center, suffering mailing disruptions due to weather, or paying for overnight shipping. The ability to submit online also provides manufacturers with an extra day to get a submission in as it eliminates the need to submit a day early to account for shipping time. This new tool benefits all stakeholders who need to submit a submission to FDA. CDRH deserves a huge kudos for their Digital Transformation Initiative and we at RQM+ are very excited to see what comes next! Looking for more FDA related content? Watch our recent RQM+ Live! show focused on the FDA Appeals Process, featuring guest panelists from Linear Health and DuVal & Associates, PA. #### Impact of FDA's Final LDT Rule: Industry Concerns and Compliance FDA released the final rule on laboratory developed tests (LDTs) on May 6, 2024. This rule brings most LDTs under the purview of FDA through the medical device regulation by including them within the definition for in vitro diagnostics (IVDs). The final rule includes a phased implementation by which IVDs offered as LDTs will need to meet the requirements of each phase as they come. This includes both LDTs currently used by clinical laboratories and new devices entering the market. The phases are shown in the table below: PhaseRequirementDeadline1Medical device reporting requirements; correction and removal reporting requirements, and complaint file quality system requirements (21 CFR 820.198)  May 6, 20252Requirements not covered in other phases including registration and listing, labelling, and investigational useMay 6, 20263Quality system requirements (21 CFR 820)May 6, 20274Premarket review requirements for high risk IVDs offered as LDTsNovember 6, 20275Premarket review requirements for moderate and low risk IVDs offered as LDTsMay 6, 2028 The rule also contains allowances for certain LDTs to benefit from full or partial enforcement discretion. The details of this can be found on the FDA website and were discussed in detail in our recent webinar. FDA has also launched a campaign to provide more information to industry for meeting these requirements. This includes both webinars and guidance documents. See below for links to some of the available content: Webinar - Final Rule: Medical Devices; Laboratory Developed Tests (held May 14, 2024) Webinar - Enforcement Policies for Certain In Vitro Diagnostic Devices - Draft Guidances (held June 5, 2024) Webinar - In Vitro Diagnostic Product (IVD): Classification (held July 16, 2024) Webinar - In Vitro Diagnostic Products (IVDs) - MDR Requirements, Correction and Removal Reporting Requirements, and Quality System Complaint Requirements (upcoming, August 22, 2024) The FDA webinars and guidance documents help provide information on the rule as well as on current practices and requirements for IVDs. However, they do not go beyond the details that can be found in the final rule, leaving some unanswered questions and ambiguity for laboratories. Many people and professional organizations in industry have been very vocal in their opposition to the final rule, with many laboratories wondering how to maintain their current test list while operating within the budgetary constraints of their organization. Many critics are also citing the final rule as FDA overreach and questioning the regulatory authority of the FDA to make and enforce such a rule. In fact, the American Clinical Laboratory Association (ACLA) along with a private laboratory, HealthTrackRx, have filed a complaint against FDA in the U.S. District Court for the Eastern District of Texas. The complaint alleges that the FDA has exceeded its statutory authority and that the final rule represents agency regulatory overreach. It also purports that the legislation is inappropriate and ill-suited for regulating LDTs. Within the final rule, FDA has outlined in great length its justification for the FDA authority over LDTs as well as the appropriateness of and need for the legislation. However, some legal experts think the lawsuit has merit, especially considering the implications of the recent Supreme Court decision regarding Chevron doctrine. Chevron doctrine previously mandated courts to defer to government agencies’ interpretation of ambiguous statutes. This doctrine has been overturned in a recent Supreme Court decision. As a result, rules set forth by agencies to clarify existing regulations may see increased scrutiny, and this includes the LDT final rule and subsequent ACLA lawsuits. There is additional uncertainty regarding the FDA final rule due to the political landscape. Considering this is an election year, and FDA officials are appointed by a new president, the outcome of the election and the identity of the next selected FDA commissioner could impact the status of the final rule. The ACLA lawsuit and current political landscape leave many laboratories wondering what steps they should be taking, hesitant to put resources toward the transition without knowing the outcome of the lawsuit. Putting off the transition could be a risky decision considering the lawsuit could take more than a year to get through the court system. Other actions by Congress to create regulations in this area (e.g. the VALID act) are expected to also take considerable time to come to fruition. With the phased transition dates starting less than one year away with medical device reporting requirements applicable starting May 6, 2025, putting off compliance could put laboratories at risk of non-compliance in the event the lawsuit is not resolved or is ruled in favor of FDA. RQM+ recommends a conservative but strategic approach to ensure compliance with the LDT final rule should the phased implementation continue. More details regarding the content of the rule as well as strategies for compliance were discussed in our webinar held last month. If you need support for your transition, please contact our team. 💡 Watch the webinar: Adapting to the New LDT Regulatory Reality: The Path to Compliance #### Inside a Hybrid Partnership: How Jordi Labs Supports MedTech Teams with On-Demand Expertise Developing medical devices and diagnostics requires rapid problem-solving, advanced testing, and seamless collaboration across scientific and regulatory domains. For MedTech companies, internal teams may be strong—but even the best teams can’t do everything alone. A hybrid partnership model offers a solution: integrating external specialists into core workflows, without losing control or cohesion. Jordi Labs, now part of RQM+, exemplifies this approach. By offering advanced chemical and material analysis as an on-demand extension of internal R&D, quality, and regulatory teams, Jordi Labs accelerates critical milestones and reduces bottlenecks. Here’s how a hybrid partnership with Jordi Labs can transform your MedTech development pipeline. What Is a Hybrid Partnership in MedTech? A hybrid partnership blends the advantages of internal team leadership with the depth and agility of external expertise. Unlike standard outsourcing, this model creates close, collaborative relationships—where external partners function as embedded team members. Core features of the hybrid model: Flexible resource augmentation without increasing headcount Direct collaboration with scientists who understand your product Scalable testing and analytical capacity on demand With Jordi Labs, MedTech teams gain continuous access to world-class chemical analysis—aligned with internal goals and timelines. The Benefits of Hybrid Collaboration With Jordi Labs 1. On-Demand Expertise When It Matters Most Chemical and material issues don’t follow a schedule. Whether you're facing a pre-submission deadline, an unexpected test result, or a materials selection decision, access to responsive expertise is critical. Jordi Labs delivers: Rapid extractables & leachables (E&L) testing and material characterization Expert interpretation of analytical results Proactive resolution of possible regulatory concerns through real-time problem-solving Guidance on regulatory and biocompatibility implications This means fewer delays, faster troubleshooting, and more confidence across design and validation phases. 2. Seamless Integration Into Internal Teams Jordi Labs doesn't operate at arm’s length. Instead, their scientists collaborate directly with your team—through joint planning, data interpretation, and regulatory alignment. Collaboration includes: Shared project plans and timelines Frequent communication and co-development of testing protocols Co-authored content for regulatory submissions (e.g., ISO 10993, FDA 510(k), EU MDR) This level of integration ensures that results aren’t just accurate—they’re actionable. 3. Accelerated Regulatory and Preclinical Readiness Jordi Labs is recognized for scientific excellence and regulator-trusted methods. Their research is often cited directly in regulatory decisions, providing credibility that accelerates the approval process. Their expertise supports: ISO 10993-18 chemical characterization ISO 10993-17 toxicological risk assesment FDA, EMA, and MDR/IVDR regulatory filings Preclinical safety assessments for novel materials and formulations Investigative resolution of complex analytical or material challenges By combining speed with scientific rigor, they help sponsors meet critical deadlines without sacrificing quality. 4. Expanded Analytical Capacity—Without Fixed Overhead Building in-house chemical analysis labs or hiring full-time experts can be costly and inflexible. The hybrid model solves this by offering access to specialized capabilities only when needed. With Jordi Labs, you gain: Over 60 analytical techniques and advanced instrumentation A team of Ph.D.-level chemists and materials scientists State-of-the-art instrumentation exceeding regulator expectations The ability to flex capacity based on project volume and urgency This is ideal for startups managing constrained budgets and enterprises juggling multiple development timelines. Real-World Applications of the Hybrid Model Material selection:Jordi supports early-stage teams by identifying safe, durable polymers and coatings, preventing downstream issues in performance or biocompatibility. Regulatory submissions:Jordi supports the full ISO 10993 submission process, with E&L data, biological testing, toxicological risk assesment and expert analysis that are trusted by regulators for their clarity, scientific rigor, and completeness. Failure analysis:When devices degrade, discolor, or malfunction, Jordi identifies the root chemical or material cause, enabling fast design corrections or CAPAs. The Integrated Strength of Jordi Labs and RQM+ As a member of the RQM+ family, Jordi Labs operates within a broader ecosystem of MedTech regulatory, clinical, and quality services. This provides clients with: Multidisciplinary expertise across product development and compliance Unified support from preclinical testing to post-market surveillance Faster problem-solving at the intersection of science and regulation Together, RQM+ and Jordi Labs provide end-to-end support that’s agile, precise, and deeply informed by real-world challenges. Looking for MedTech Support? The hybrid partnership model with Jordi Labs allows MedTech innovators to extend their capabilities without adding complexity. Whether navigating regulatory hurdles, refining material choices, or resolving unexpected test results, Jordi provides the expertise, speed, and flexibility that modern development demands. Backed by RQM+, this partnership empowers teams to move faster, solve smarter, and deliver safer devices to market. In today’s MedTech landscape, hybrid collaboration isn’t just efficient—it’s essential. Contact us to talk MedTech support today.  #### Insight into RQM+ Consultation: How the Most Appropriate Study Design is Determined A clinical study design describes the methodology with which to pursue the aims and objectives of a clinically important research question in a target population. When reaching out to us at RQM+, we bring on board a range of internal stakeholders to deliberate with you the descriptors of your target populations, endpoints, study duration and designs. These are all budget relevant variables. Regulatory and ethical frameworks are considered alongside the intended analyses of study data. Being a full-service clinical research organization (CRO), we aptly assist in delineating objectively the suitability of an experimental or observational strategy to address a given clinical need in any medical discipline, including dentistry. The regulatory framework is provided by the Medical Devices Regulation (EU) 2017/745. According to MDR Article 2 (45), the motivation to conduct a clinical investigation is to assess the safety or performance of a device in human subjects. Data integrity and subject safety are operationalized in ISO 14155 (the standard for Clinical investigation of medical devices for human subjects — Good clinical practice) and - importantly - are within the principal investigator´s remit. The ethical caveat for clinical research is to safeguard patient safety and rights and minimize unintentional harm or burden whilst pursuing to the highest scientific standards a topical question of medical relevance (Declaration of Helsinki). A robust study design as well as the validity of the study data hinge on the manufacturer´s statement of intended use. Clinical performance of the device entails use of the device as intended by the manufacturer and should be clearly specified in an investigation. Safety of using the medical device must be monitored. Together, the assessments of clinical performance and safety will capture the clinical benefit of a medical device, i.e., according to MDR Article 2 (53), “the positive impact of a device on the health of an individual (…) or a positive impact on patient management or public health”. The outcomes of the investigation should be meaningful, measurable, patient-relevant and related to the diagnosis, according to MDR. The intention of this article is to present an insight into the reasoning behind proposing certain designs of study, drawing from relationships with clients that have led to peer reviewed publication of their research activity (e.g., Park et al., 2022; Amin et al., 2024) and wider consulting activity. Two common discussion scenarios are chosen to showcase RQM+´s input in your strategic decisions on the best choice of a study design for your intended investigation. The designating term `participant´ for the individual contributing to clinical research through their voluntary participation shall be used were applicable, in replacement of the term 'subject' (Corpuz, 2023). Glossary of technical terms TermDefinitionCLINICAL INVESTIGATIONAny systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device. Art 2(45), MDR (Medical Device Regulation)EFFICACYIs the ability of a medical device to produce the desired effect.EFFECTIVENESSIs the measure of clinical benefit when used in the real world REAL WORLD DATA Patient and health care data collected from a variety of sources, excluding controlled trialsREAL WORLD EVIDENCEClinical evidence about the usage and potential benefits or risks of a medical device derived from analysis of real-world data  For a controlled investigation – Randomized controlled trial (RCT) or Cross-over design? Interventional studies, i.e. studies in which exposures / treatments are assigned, have the strongest evidence of cause-effect relationships. In fact, they are the gold standard to test the efficacy of the treatment and are especially impactful for public health policy. To unequivocally demonstrate a treatment effect, a comparison to a control is required. A control group is a group which does not receive intervention with the investigational device. In statistical terms, the effect is termed 'Outcome variable', the cause is the so-called 'Treatment variable'. A covariate is a 'Confounding variable', a variable that influences both the selection of treatment and the outcome variables. We help to define and advise on these, as they are relevant for the level of statistical analyses the investigation will require. To eliminate selection bias and reduce confounding variables, a process termed randomization is used. In this process, participants who satisfy inclusion and exclusion criteria are randomly allocated to the intervention or control group. In this manner, hypotheses can be tested. To describe interventionist trials (they can be either RCT or follow a cross-over design), we use the PICO scheme. The scheme, essentially a brief table, crystallizes for quick reference and comparison to benchmarks, which we assist in, study population, type of intervention, control and outcomes. The scheme can be expanded by the investigation’s setting and the timeframe (PICOST). Study outcomes need to be seen in the context of clinical relevance, participant adherence measures and patients´ own reported outcomes whilst considering likely confounders. To define 'control' in the medical device field, we need to critically revisit the concept that placebos are inert: A Cochrane criterion-based, seminal analysis of contextual effects in RCT finds that over half of the overall treatment effect could be due to the placebo response i.e., the contextual response to a placebo effect (Hafliðadóttir et al., 2021). This observation may explain the so-called efficacy paradox, i.e. the lack of reproducibility of RCT-described efficacy in clinical practice, where contextual effects contribute to the overall treatment effects (Zhang and Doherty, 2018). However, patient-provider interactions and patient expectations of treatment are contextual factors whose relative impact on study results may equalize when the study is multicentric. The implications are that the treatment of the control arm needs to be accurately defined and evaluated against routine practice in order to more accurately gauge a treatment effect. This is because the beneficial effect of placebo interventions is measurable and varied (Hróbjartsson and Gøtzsche, 2010). A more recent school of thought tries to engage with the placebo effects by viewing them as a threshold which the treatment needs to surpass to be deemed efficacious. This is because “therapeutic alliance and the beliefs and expectations of patients” engender placebo responses and should therefore be harnessed (Friesen, 2019). RQM+ is equipped to discuss these aspects in relation to the number of sites you have in mind for your investigation. In a randomized control trial, participants are randomly allocated to one of more study arms where one arm during the same study period does not receive the intervention of interest. In a cross-over design, randomized participants furnish their own control, and all will receive the intervention by the end of the study. Figure 1 illustrates the difference. A B Figure 1. Schematic representation of RCT (parallel design) (A) and randomized trial in crossover design (B). Since each patient is his or her own baseline in a cross-over design, fewer patients may be required compared to the RCT design, but the study duration is longer. Because treatment and periodic effects are separated in a cross-over design, hangover effects are meant to be eliminated by a wash out phase, i.e. an interim phase between one treatment and another, when the randomized group is switched between arms. To discern a treatment effect, a special statistical method needs to be used (analysis by sequency group; Wellek and Blettner, 2012). It is important in clinical trials to document the disposition of participants, i.e. the extent to which participants have reached the intended trial milestones. For RCT and cross-over design alike, participant attrition requires adequate statistical planning (Bell et al., 2013). RQM+'s statistical team is poised to explain. Clinical monitoring of inclusion, disposition, endpoint relevant data points and safety should be well defined in support of the integrity of conclusions reached (Hsieh et al., 2023). RQM+'s clinical monitoring team is well trained to deliver on these points. Because of the cross-over design, participants dropping out of the investigation may signify an attrition that jeopardizes attaining the endpoints of the study. It is also debatable whether patients at the timepoint of crossing over are truly comparable to the study start, especially when the study entails a behavioral change, entertains an expectation, or exerts a training effect to where the patients become more attuned to the study requirements. In fact, a cross-over design is not the experimental method of choice where the operator of a medical device is herself or himself on a learning curve (Bernard et al., 2014) or if the disease that is investigated is rapidly progressive (Zhang et al., 2022). RQM+'s consulting team will critically evaluate with you factors that are relevant to your intended investigation. Adaptive designs are a statistical means to prospectively plan a pre-specified study modification (Pallmann et al., 2018). They are applicable to RCT (Bernard et al., 2014) and cross-over trials (Cook and Willan, 1996) and are advisable when the numbers of patients to recruit to the study need to be reviewed based on the primary outcome measures. This can be useful in the strategic management of your intended investigation. RQM+'s statistical team will address the use of adaptive designs in client consultations. For real world evidence – medical chart review or device registry study? Observational studies pursue a topical research question that has arisen from within routine medical practice. They may, during data collection and analysis, generate novel hypotheses for future clinical research. Observational studies are by definition 'non-interventional'. Typically, the extent of inclusion and exclusion criteria is much curtailed compared to interventional trials. Fringe populations may find representation in observational studies while they are typically not included in randomized in trials – which categorically aim to minimize influence of confounding factors (see above). For this reason, the outcome of observational studies is more generalizable to all patients receiving care for the same diagnosis (Kennedy-Martin et al., 2015). Observational studies collect adherence data and data relating to safety and performance that may impact on the risk benefit analysis of a medical device, providing real-world evidence. Possibly off-label use may be found and requires stringent assessment (Team-NB position paper, 2022). The strength of observational studies is to capture the extent of real-world adherent behavior as well as treatment decisions that determine the effectiveness of a medical device (Gliklich et al., 2014). Real-world data are data relating to patient health status and/or the delivery of health care and can be collected from a variety of sources, including patients' medical files in so-called chart review studies. Another example of real-world data is data derived from device registries.  Both, device registries and chart reviews can provide clinical evidence on “real-world effectiveness and (…) start to address the complications of managing other real-world problems such as multimorbidity” (de Lusignan et al., 2015). Device registries and chart reviews typically differ in size, extent of multicentricity, duration of data collection and the extent to which additional market relevant information of interest to the manufacturer is collected. Guidance on the conduct of a retrospective chart review has been published (Vassar and Holzmann, 2013; Sarkar and Seshadri, 2014) and informs RQM+'s consulting. Particular attention should be paid to best practice in avoiding extraction and analysis bias (Kaji et al., 2014). RQM+ can assist in providing adequate training at the sites. In the design of registries, the inclusion of long-term follow-up data is important. To analyze study data emanating from observational studies, specific statistical tools are required, such as stratification into clusters of patients with similar characteristics prior to analysis (Carragher et al., 2020) or so-called propensity score matching to reduce the effect of systematic confounding at baseline in nonrandomized observational studies (Austin, 2011). RQM+'s statistical team routinely conducts these.   Consecutive enrolment of patients against wide inclusion and exclusion criteria allows long-term data collections from routine care. These studies are important in the assessment of medical device safety and may have prospective and retrospective components by design. Why are these important? Prospective studies have the advantage of being able to include measurements of risk factors, though detection of long-term effects may be limited by the period of follow-up. Retrospective studies are ideal in the study of rare diseases (Talari and Goyal, 2020). Observational prospective studies require clinical monitoring and site oversight. Monitoring of retrospective observational studies, by contrast, concentrates on completeness and accuracy of data entries from hospital records. Missing data typically are due to loss to follow-up (prospective) or incomplete data sets (retrospective). RQM+'s statistical team routinely considers their potential impact on the study's outcome in a statistical analysis plan. Concluding statement  Randomized trials are more likely to discern cause and effect because the process of randomization reduces the bias through confounding variables. However, a disproportionate drop out of participants may still alter the validity of the outcome of the investigation. Therefore, ensuring participation (treatment adherence and protocol compliance) is an important factor RQM+ will consider when setting up your clinical investigation. Observational studies work out a quantitative relationship of variables, termed statistical association. They pursue a clearly defined research question which RQM+ can help to refine and support in its novelty through a systematic literature search. An expert statistical team is required for the analyses.  Key elements in the discussions of clinical study design have proven to be client´s and RQM+´s views of representativeness of the study population and generalizability of outcomes, operationalizing the manufacturer’s claims on the medical device (definition of endpoints), a priori decisions on subgroup analyses in support of the claims, type and frequency of clinical monitoring activities (dependent on the study design, see above). To realize scientific integrity in medical device research, RQM+ refers to published guidelines for the design of medical device studies across device lifecycles and regulatory need (Fleetcroft et al., 2021). RQM+'s consulting team also speaks to the justification of protocols through scientific peer review: STaRT-RWE (Wang et al., 2021) and CONSORT (Schulz et al., 2010) are guidelines for the conduct of real-world evidence studies and parallel group randomized trials, respectively. Publication of protocols allows for greater transparency in the clinical research community which, for the same reason, is called to publish their studies in searchable clinical trial databases such as clinicaltrials.gov or national study registries. The process of publishing a study protocol ensures a quality standard with which clinical research should be conducted and which RQM+'s medical writers aptly support. To summarize, the balancing of the most appropriate study design (randomized controlled vs observational) in the medical device field is a highly topical issue (Páez et al., 2022) that RQM+ will help to view from within our common ethical framework to yield efficient and cost-effective solutions. Importantly, both designs have their value in generating clinical evidence (Monti et al., 2018) and can be efficiently tailored to the stage of development and market presence of the medical device. At RQM+, the clinical trial business unit offers the entire wealth of experience and expertise to anticipate risks and realize potential of your intended investigation. Partner with us to ensure your clinical investigations are designed with precision, executed flawlessly, and deliver the data you need to succeed. In case you missed it, take a look at our latest related technical brief, Determining the Primary Endpoint in Clinical Research. Join us on the 12th of December, 2024 for RQM+ Live! Medical Device Cybersecurity: Proven Strategies for Connected Devices and SaMD and be sure to bring your questions for our expert panelists! Medical Device Cybersecurity RQM+ Live References Amin M, Abdrakhmanov A, Kropotkin E, Traykov V, Salló Z, Gellér L, Lorgat F, Sapelnikov O, Toman O, Al-Muti K, Aljaabari M, Bystriansky A, Környei L, Mujović N, Simons S, Szegedi N. Ablation of Supraventricular Arrhythmias With as Low as Reasonably Achievable X-Ray exposure (AALARA): Results of Prospective, Observational, Multicenter, Multinational, Open-Label Registry Study on Real World Data Using Routine Ensite 3D Mapping During SVT Ablation. Pacing Clin Electrophysiol. 2024 Sep 27. doi: 10.1111/pace.15075. Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011; 46(3):399-424. doi: 10.1080/00273171.2011.568786. Bell ML, Kenward MG, Fairclough DL, Horton NJ. Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ. 2013; 346:e8668. doi: 10.1136/bmj.e8668. Bernard A, Vaneau M, Fournel I, Galmiche H, Nony P, Dubernard JM. Methodological choices for the clinical development of medical devices. Med Devices (Auckl). 2014; 7:325-34. doi: 10.2147/MDER.S63869. Carragher R, Mueller T, Bennie M, Robertson C. A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data. Stat Med. 2020; 39(20):2639-2654. doi: 10.1002/sim.8563. Cook RJ, Willan AR. Design considerations in crossover trials with a single interim analysis and serial patient entry. Biometrics. 1996; 52(2):732-9. Corpuz JC. Reconsidering the Terminology: Study Participants as "Subjects" or Not? Subst Abuse. 2023; 17:11782218231217783. doi: 10.1177/11782218231217783. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Accessed 11.10.2024, accessible at  https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ de Lusignan S, Crawford L, Munro N. Creating and using real-world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015; 22(3):368-73. doi: 10.14236/jhi.v22i3.177. Fleetcroft C, McCulloch P, Campbell B. IDEAL as a guide to designing clinical device studies consistent with the new European Medical Device Regulation. BMJ Surg Interv Health Technol. 2021;3(1):e000066. doi: 10.1136/bmjsit-2020-000066. Friesen P.   Mesmer, the placebo effect, and the efficacy paradox: lessons for evidence based medicine and complementary and alternative medicine. Critical Public Health 2019, VOL. 29, NO. 4, 435–447 doi:10.1080/09581596.2019.1597967 Gliklich RE, Dreyer NA, Leavy MB, editors. Registries for Evaluating Patient Outcomes: A User's Guide [Internet]. 3rd edition. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Apr. 3, Registry Design. Available from: https://www.ncbi.nlm.nih.gov/books/NBK208632/ Hafliðadóttir SH, Juhl CB, Nielsen SM, Henriksen M, Harris IA, Bliddal H, Christensen R. Placebo response and effect in randomized clinical trials: meta-research with focus on contextual effects. Trials. 2021; 22(1):493. doi: 10.1186/s13063-021-05454-8. Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010; 2010(1):CD003974. doi: 10.1002/14651858.CD003974.pub3. Hsieh SF, Yorke-Edwards V, Murray ML, Diaz-Montana C, Love SB, Sydes MR. Lack of transparent reporting of trial monitoring approaches in randomised controlled trials: A systematic review of contemporary protocol papers. Clin Trials. 2023; 20(2):121-132. doi: 10.1177/17407745221143449. Kaji AH, Schriger D, Green S. Looking through the retrospectoscope: reducing bias in emergency medicine chart review studies. Ann Emerg Med. 2014; 64(3):292-8. doi: 10.1016/j.annemergmed.2014.03.025. Epub 2014 Apr 18. PMID: 24746846. Kennedy-Martin T, Curtis S, Faries D, Robinson S, Johnston J. A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results. Trials. 2015; 16:495. doi: 10.1186/s13063-015-1023-4. Monti S, Grosso V, Todoerti M, Caporali R. Randomized controlled trials and real-world data: differences and similarities to untangle literature data. Rheumatology (Oxford). 2018; 57(57 Suppl 7):vii54-vii58. Páez A, Rovers M, Hutchison K, Rogers W, Vasey B, McCulloch P; IDEAL Collaboration. Beyond the RCT: When are Randomized Trials Unnecessary for New Therapeutic Devices, and What Should We Do Instead? Ann Surg. 2022; 275(2):324-331. doi: 10.1097/SLA.0000000000005053. Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JMS, Weir CJ, Wheeler GM, Yap C, Jaki T. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 2018;16(1):29. doi: 10.1186/s12916-018-1017-7. Park KJ, Meißner T, Günther E, Schmalz G, Kottmann T, Krause F, Haak R, Ziebolz D. Arrest of root caries with an adjuvant chlorhexidine-fluoride varnish over a 12-months observation period: a QLF-analyzed, placebo-controlled, randomized, clinical trial (RCT). Odontology. 2022;110(1):193-202. doi: 10.1007/s10266-021-00637-w. Sarkar S, Seshadri D. Conducting record review studies in clinical practice. J Clin Diagn Res. 2014; 8(9):JG01-4. doi: 10.7860/JCDR/2014/8301.4806. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010; 340:c332. doi: 10.1136/bmj.c332. Talari K, Goyal M. Retrospective studies - utility and caveats. J R Coll Physicians Edinb. 2020;50(4):398-402. doi: 10.4997/JRCPE.2020.409. Team-NB position paper “Data generated from ‘Off-Label’ Use of a device under the EU Medical Device Regulation 2017/745.” accessed 14.10.2024, accessible at https://www.team-nb.org/wp-content/uploads/2022/10/Team-NB-PositionPaper-Off-LabelUse-V1-20221005.pdf Vassar M, Holzmann M. The retrospective chart review: important methodological considerations. J Educ Eval Health Prof. 2013; 10:12. doi: 10.3352/jeehp.2013.10.12. Wang SV, Pinheiro S, Hua W, Arlett P, Uyama Y, Berlin JA, Bartels DB, Kahler KH, Bessette LG, Schneeweiss S. STaRT-RWE: structured template for planning and reporting on the implementation of real world evidence studies. BMJ. 2021; 372:m4856. Wellek S, Blettner M. On the proper use of the crossover design in clinical trials: part 18 of a series on evaluation of scientific publications. Dtsch Arztebl Int. 2012;109(15):276-81. doi: 10.3238/arztebl.2012.0276. Zhang W, Doherty M. Efficacy paradox and proportional contextual effect (PCE). Clin Immunol. 2018; 186:82-86. doi: 10.1016/j.clim.2017.07.018. Zhang B, Guo J, Zhang H. Design and analysis of crossover trials for investigating high-risk medical devices: A review. Contemp Clin Trials Commun. 2022; 30:101004. doi: 10.1016/j.conctc.2022.101004. #### Intended Use: Foundation stone, guiding light or just a box to tick? By Ed Ball, CEng, MIPEM, MIMMM – Manager, Intelligence & Strategic Execution Delays! Rejections! Frustrations!  Inconsistent descriptions of the intended use throughout the submitted technical documentation is commonly cited as the reason for Notified Body questions during EU MDR assessments. Incorrect assignment of the product code or inappropriate selection of a predicate device, based on a poorly defined intended use, can lead to significant delays or failures in US 510(k) submissions.  Introduction   Hopefully most readers of this blog appreciate the importance of the intended use in the design, development, conformity assessment and marketing of a medical device. The intended use should be the starting point for product development and risk management activities. In most established medical device regulatory frameworks, the intended use is fundamental to the conformity assessment of the device. The intended use drives:  the classification of the device, and thus the conformity assessment pathway; the level of objective evidence required to demonstrate that the device is safe and effective; the specific document types required by a regulation; the standards applicable for the device; the suitability for national reimbursement categories; and the resulting surveillance activities once the device is on the market. The intended use is therefore a significant factor that affects the overall timeline for developing and launching a medical on a specific market. The elements of the intended use are thus critical to premarket regulatory strategies, reimbursement strategies and commercial strategies for sales and marketing.  But what is the intended use?   It is unlikely to be single sentence or statement, I am fairly sure of that. The various facets of the intended use are not something that can be condensed into a short pithy one-liner, without a significant loss of detail and specificity. Although, specific regulatory authorities may require such a statement or headline to act as a summary for all the detail that lies beneath. For example, relying solely on a intended use statement to underpin the technical and clinical evidence to support a submission under the EU MDR or IVDR is likely to be a flawed approach. The use of a high-level statement will likely leave gaps and misalignment when it comes to identifying similar products, identifying and interpreting your user needs, collecting and analysing clinical data, and establishing relevant clinical performance outcomes. None of which are positive when it comes to a successful conformity assessment.  It is unlikely to be single sentence or statement. How is it defined?   A time-consuming trawl through the ISO Online Browsing Platform, various ISO and IEC standards, several key regulations and numerous IMDRF and GHTF guidance documents gave me the information I was seeking. Regulations do not specify the source (either direct copy or of the ‘inspired by’  indirect variety) for the legally defined terms and definitions, but ISO and IEC standards usually do. Through various convoluted family trees and revision trees, I can tell you that for those medical device standards that define intended use (or intended use / intended purpose as synonym) and cite a source for their reference they lead back to one of the following three documents:   ISO IEC Guide 63:2019 (Guide to the development and inclusion of aspects of safety in International Standards for medical devices),   IMDRF/GRRP WG/N47:2024 (Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices), or   IMDRF/GRRP WG/N52 FINAL:2024 (Principles of Labeling for Medical Devices and IVD Medical Devices).   It is worth noting that several of the references to ISO IEC Guide 63:2019 are indirect, often via ISO 14971:2019 which uses Guide 63 as its source reference for the definition of ‘intended use’. It should also be noted that the definition in the above two IMDRF guidance documents is the same, where N47 has two Notes to the entry and N52 only includes the second of those two notes. It is also noteworthy that ISO 13485:2016, despite being a major part of the global medical device landscape, neither defines intended use (or intended purpose) nor explicitly requires it to be determined or documented - although it remains essential to embed intended use clarity within your broader quality management system and regulatory strategy. I can wait whilst you go and check for yourself if you’d like.  Comparing the definitions from these three sources plus those from the EU MDR, EU IVDR and US 21 CFR 801.4 (Table 1), there is good consistency. One could argue that the use of ‘intended purpose’ in the EU MDR and IVDR, alongside the frequent reference to ‘intended use’ in the legislation, could be considered (from a technical perspective, but not necessarily a legal perspective) to treat intended use and intended purpose as synonyms just like ISO 14971:2019. My personal opinion is that they can be treated synonymously and efforts to make them distinct could lead to more confusion in interpretations and usage.  ISO IEC Guide 63:2019 3.4 intended use use for which a product, process or service is intended according to the specifications, instructions and information provided by the manufacturer (3.6) Note 1 to entry: The intended medical indication, patient population, part of the body or type of tissue interacted with, user profile, use environment, and operating principle are typical elements of the intended use. IMDRF/GRRP WG/N52 FINAL:20243.14. Intended Use / Intended Purpose:The objective intent regarding the use of a product, process or service as reflected in the specifications, instructions and information provided by the manufacturer. (Modified from GHTF/SG1/N77:2012) NOTE 1: The intended use/intended purpose are also part of promotional or sales materials or statements, although these materials lie outside the scope of this document. NOTE 2: The intended use can include the indications for use. EU MDR 2017/745 Art 2. (12) ‘intended purpose’means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation; EU IVDR 2017/746Art 2. (12) ‘intended purpose’means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements or as specified by the manufacturer in the performance evaluation; 21 CFR 801.4The words intended uses or words of similar import in §§ 801.5, 801.119, 801.122, and 1100.5 of this chapter refer to the objective intent of the persons legally responsible for the labeling of an article (or their representatives). The intent may be shown by such persons' expressions, the design or composition of the article, or by the circumstances surrounding the distribution of the article. This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives.  Table 1. Collated definitions of intended use  Regardless of the source, ‘intended use’ can be summarised as “the use of a device, product or service as intended by its manufacturer”. The intent of the manufacturer can be communicated and conveyed via various forms, depending on the source material for the definition.  But what does that mean in practice?  With the definition sorted we can then dig into more detail of what it means in the context of the medical device industry. For this I prefer to fall back on two standards and their associated guidance documents (all about risk management, who’d have thought it?):  ISO 14971:2019 Medical devices — Application of risk management to medical devices  ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO 14971  IEC 62366-1:2015/Amd 1:2020 Medical devices Part 1: Application of usability engineering to medical devices  IEC/TR 62366-2:2016 Medical devices Part 2: Guidance on the application of usability engineering to medical devices  Additionally, the IMDRF definition for intended use indicates that the ‘indications for use’ is a component of the intended use. The IMDRF also add further clarity where IMDRF/GRRP WG/N52 FINAL:2024 also defines ‘indications for use’ and positions the intended patient population as a component of the indications for use. Appreciating the relationships between these terms (see Figure 1) and how they combine to build the overall intended use is key. A thorough understanding of the intended use, and the subsequent development and post-market activities, are fundamental to effective product stewardship.  In summary, it boils down to the answers to key questions along the lines of: Who? What? Where? Why? When? How? Figure 1. The building blocks of the intended use  Therefore, a reasonable description of what comprises the intended use can thus be summarised as the intended:  medical indication(s), including patient population(s) and sub-populations,  part of the body or type of tissue applied to or interacted with,  user profile(s), e.g.  analytical user vs clinical user (for IVDs, other diagnostics, measuring devices and classification tools),  professional vs lay-person,  role of professionals in the life cycle of the device,  use environment(s), e.g.  clinical setting vs home setting vs others (e.g. a school, public spaces),  large, state-of-the-art hospitals vs rural community hospitals vs multidisciplinary outpatient clinics,  operating principle / mode of action (of the device),  clinical procedure (i.e. for the use of the device etc.),  clinical context (e.g. where/when in the clinical pathway will the device be used?),  accessories (i.e. used to fulfil the intended use of the device),  adjunctive devices &/or therapies (i.e. used in conjunction with the device for its intended use, or typically in use on/by the intended patient population).  With this in mind, it should be evident that this holistic view of the intended use (Firgure 1) is then crucial for all the efforts to develop the product (e.g. setting the scene for design and development inputs, framing the context for the risk analysis), traverse the chosen/prescribed conformity assessment pathway (e.g. classification, clinical evidence strategy) and actually market and sell the device to the intended customers and users (e.g. reimbursement, customer sales).  “I hear what you’re saying, but our device is really complicated, and the intended use is tricky to pin down”. I’m not buying that argument! Apply the simplistic logic described above and you will understand, and be able to describe, your intended use much better than before. Regardless of the technology or product type, asking these simple questions helps you understand your product, helps you identify safety characteristics and potential risks, and helps you generate objective evidence to demonstrate that your device is safe, effective and (hopefully) cost-effective for its users.  What happens if insufficient detail is given in the description of the device’s intended use? Therein lies protracted development timelines and delayed market launches. For example, delays can occur due to things like clinical evidence not aligning to the intended claims, or because the clinical data does not address all of the indications for use, or the usability of the user interface has not been assessed for all of the intended user groups.   Insufficient detail in describing the intended use can also lead to troubles in the post-market phase, during post-market surveillance. For example, with the need for multiple design changes required to adjust to multiple customer requirements that were not considered during development, or performing many iterative cycles through the risk management cycle as new use errors and hazardous situations are identified as the difference between the anticipated use and the actual use becomes apparent. More on the last one to come in a subsequent blog.  Is there ever a final intended use?  Only in the same way that there is a design freeze or design lock for the design of the medical device. It is a state of being, but it is not permanent. Change is a constant (someone wiser than me said that I think), otherwise there would be no need for change management activities. For any organisation thinking that the intended use defined at the start of the design and development inputs or that defined in a regulatory strategy is the definitive intended use, think again. There are numerous anecdotal tales of EU MDR submissions where the intended use has been refined over time but has left a misalignment between the clinical evaluation, and/or the risk management, and other parts of the technical documentation. In reality, we start with a rough outline of the intended use as we start product development. Over time, we add detail to that outline and we edit as we move along, uncovering new evidence, making new decisions. Maintenance activities occur naturally during the life cycle of the device, modifying and updating your device, objective and parameters. As Figure 2 suggests, the general outline is often in place from the start but by the time we launch the device to market, or many years after initial launch, the outline may have changed with time and/or may have been updated as our understanding of the details increases.  Figure 2. The iterative nature of the intended use throughout the medical device life cycle (travelling left to right)  And all of this leads into the realisation that the identification of reasonably foreseeable misuse, including off-label use is not as difficult as some in the industry make out. If we see the intended use as something that is iterative, that evolves through development and life cycle management (Figure 2), then reasonably foreseeable misuse can be anticipated (often by channelling your inner 3-year-old and just asking, Why? or What if?). When the intended use does change, that change should be managed just like any other change at that stage of the life cycle (e.g. a design and development change, change control of a marketed product). That is not to say that all such uses will be anticipated, in the same way that we cannot be expected to identify every possible risk during product development. The unknown unknowns are there to be uncovered.  As the medtech landscape grows more interconnected, personalized, and fast-moving, good product design should be our driver not simply regulatory compliance. ‘Intended use’ is not merely a checkbox; it’s the architectural blueprint of regulatory success, clinical relevance, and commercial viability. Misunderstand it, and you risk misaligning every downstream function. Join me in Amsterdam at the 2025 International Conference on Medical Device Safety Risk Management, where I will unpack these nuances with clarity, dry sarcasm, and maybe a little regulatory heresy. Let’s stop treating intended use as an afterthought and start treating it as a living hypothesis that evolves with our technologies, our users, and our responsibilities. Bibliography:  ISO IEC Guide 63:2019 Guide to the development and inclusion of aspects of safety in International Standards for medical devices  ISO 14971:2019 Medical devices — Application of risk management to medical devices  IMDRF/GRRP WG/N47:2024 (Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices  IMDRF/GRRP WG/N52 FINAL:2024 (Principles of Labeling for Medical Devices and IVD Medical Devices).  21 CFR 801.4 Meaning of intended uses (last checked 11 April 2025)  ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO 14971  IEC 62366-1:2015/Amd 1:2020 Medical devices Part 1: Application of usability engineering to medical devices  IEC/TR 62366-2:2016 Medical devices Part 2: Guidance on the application of usability engineering to medical devices  EU MDR 2017/745  EU IVDR 2017/746  #### ISO 10993-1 6th Edition is Here – Are You Ready? The 6th edition of ISO 10993-1 is published! It brings significant updates for biological evaluation processes in medical device development. While it’s not a mandate for new testing, manufacturers will need to assess existing processes and evaluations against the revised framework. Key Changes You Need to Know Stronger integration of biological evaluation with risk management ISO 10993-1 has long been part of risk management but the changes made to this 6th edition emphasize this point throughout. The updated standard brings with it an expectation that the biological evaluation process and the risk management process are interrelated and interoperable. Some elements are new to biological evaluation (e.g. reasonably foreseeable misuse) but should not be new since they are established elements of an ISO 14971 risk management process. Updated terms, definitions, and categorization criteria. Categorization terms and the method for calculating contact duration have been significantly updated. While this will impact every manufacturer’s biological evaluation process, it is most likely to have more impact on those categorization of devices with transient contact and intermittent contact but frequent or cumulative use.  Expanded consideration of biological effects and reasonably foreseeable misuse.  Biological endpoints are no more, they are now biological effects. To emphasize to readers that this is not a checklist process, the old Annex A table has been split up into four new tables with additional considerations for each device category. Reasonably foreseeable misuse should be considered when re-evaluating based on updated device category. What Does This Mean for You? Assess the differences between your current biological evaluation process and the requirements and contents of ISO 10993-1:2025. The significance of those differences will influence how quickly you need to update your process and assess your existing biological evaluations. For medical devices on the market, their biological evaluation does need to be assessed to determine whether the device needs to be categorized differently, whether additional biological effects need to be considered and thus whether there is a need for additional data. None of this can happen instantaneously, so the important aspect is for this to be driven by your gap assessments and be proportionate to the risk. The same applies for medical devices currently under development. Citing the 2018 edition of the standard will be of no use at the point of conformity assessment if you don’t understand the impact of the updates on your process and your product. Regulatory acceptance of this 6th edition will vary by region. Continue to monitor the applicable regulatory authorities and their response to this 6th edition to help you assess the impact on your products and process, and to help you prioritize specific devices and biological testing as necessary. How RQM+ Can Help: Training on ISO 10993-1 changes. Gap assessments for your processes. Remediation and updates for biological evaluations and risk management files. Biocompatibility testing, chemical characterization, and toxicological risk assessments. Don’t wait for compliance challenges—start planning now to stay ahead of regulatory expectations. Contact us today to learn how RQM+ can support your transition to ISO 10993-1:2025. #### ISO 10993-18 Is Changing. Here’s What MedTech Teams Keep Getting Wrong The science of extractables and leachables (E&L) testing for medical devices is evolving quickly, as are the associated regulatory standards. In fact, change sometimes happens so quickly that the approach that was defensible when you started your program may not be defensible by the time it reaches a reviewer’s desk. We see this pattern across dozens of submissions and labs every year. Companies typically aren’t failing because they lack technical capability. Rather, they’re falling behind because expectations are moving, and most E&L programs are built to meet yesterday’s standards. Here’s what we consistently see going wrong and what it takes for you to get ahead of it. The Pace of Change Is the Real Challenge When we ask teams what’s hardest about ISO 10993-18 chemical characterization, the answer is rarely a specific technical requirement.¹ It’s keeping up. Smaller MedTech companies with fewer devices in the market see fewer regulatory questions, which limits their exposure to evolving practices. On the one hand, that seems like it might be a good thing. However, they’re not getting the real-time feedback that larger companies receive, so they don’t see the shift in expectations until it shows up as a delay or a deficiency letter. The result is reactive compliance instead of proactive strategy. And reactive compliance is expensive. Pattern 1: Meeting Minimums Without Scientific Defensibility Most E&L programs we review fall short in that they meet minimal expectations but lack strong scientific backing. FDA reviewers are asking increasingly granular questions about extraction methods, storage conditions, and quantification approaches.² These aren’t trick questions. They’re testing whether your program is built on a defensible scientific foundation or if you’re just checking boxes. The programs that hold up under scrutiny go beyond the minimum. They document method capabilities, justify method selection based on device chemistry, and demonstrate how their analytical approach covers the relevant chemical space. That extra rigor builds trust and reduces future pushback. Pattern 2: Underestimating the Shift Toward Identification Confidence The Analytical Evaluation Threshold (AET) is well understood at this point.³ But the next big challenge is building confidence in chemical identification itself. We expect upcoming revisions to ISO 10993-18 to place even greater emphasis on identification accuracy.4 The question regulators are asking is “How confident are you that you found the right thing?” This is because of a shift toward more precise and reliable identification as a core regulatory expectation. And this is across the board — not just for high-risk devices. Pattern 3: Quantification Gaps That Surface Too Late The other side of the accuracy equation is quantification. Multiple programs run into trouble because a significant portion of chemicals observed in extractables studies cannot be matched with empirical standards. Sometimes the reference standard simply doesn’t exist. Sometimes synthesis is impractical. Either way, you’re left with a gap that shows up in your risk assessment. This is where a risk-based E&L strategy becomes essential. Predictive response factors for E&L can fill part of that gap, using chemical properties to model instrument responses for tentatively identified compounds. That improves quantification accuracy without waiting for empirical data that may never come. But predictive modeling isn’t a magic fix. It works for tentatively known compounds, but complete unknowns still require chemist expertise to identify chemical class or structure before modeling can be applied. The keys are knowing when prediction is appropriate and documenting that rationale clearly. Notably, Lumo™ needs a structure to work from, but the precision of that structural identification is less critical to quantification accuracy than it would be under traditional approaches. Pattern 4: Treating ISO 10993-18 as the Only Moving Target It’s vital to understand that the changes aren’t limited to ISO 10993-18. USP chapters on extractables and leachables assessment are evolving.5,6 Industry working groups are publishing new recommendations, and FDA interpretations are shifting based on what reviewers see in real submissions.² Companies that focus narrowly on a single standard often miss the broader pattern and end up navigating conflicting expectations without a clear strategy. The companies that stay ahead treat E&L as a system, not a checklist. They partner with labs that understand the full landscape and can adapt quickly as expectations shift. What “Modernized” Actually Looks Like We’re not suggesting that every program needs to be rebuilt from scratch. But we are suggesting that “good enough” conservative defaults aren’t good enough anymore. A modernized E&L program: Applies more rigorous testing where toxicology indicates higher risk, not uniformly across all materials Documents method capabilities and true accuracy assessments for each study Uses predictive modeling where empirical standards are unavailable and documents the rationale Treats early design decisions as upstream factors that influence downstream E&L outcomes Partners with a lab that understands the rapid pace of change and can adapt with you The science supports better outcomes than most programs currently achieve. The question is whether your program is built to capture them. Frequently Asked Questions How often is ISO 10993-18 updated, and how do I stay current? ISO 10993-18 was last revised in 2020, but regulatory interpretation evolves continuously based on submission outcomes, FDA feedback, and industry working group recommendations.¹,² The standard itself may not change annually, but expectations around defensibility, identification confidence, and quantification rigor shift faster than the document cycle. Partnering with a lab that sees patterns across many submissions is one of the most reliable ways to stay ahead. What’s the difference between meeting ISO 10993-18 requirements and having a defensible E&L program? Meeting requirements means hitting the thresholds and deliverables the standard specifies. Defensibility means your program can withstand detailed regulatory questions about why you made specific method choices, how confident your identifications are, and whether your quantification approach accounts for response factor variability. The programs that hold up document their rationale, justify method selection based on device chemistry, and go beyond minimum expectations where risk warrants it. When should I use predictive modeling instead of empirical standards for quantification? Predictive modeling is not limited to situations where empirical standards are unavailable. Applying predictions across all compounds in a study is still a stronger approach than traditional methods, even where some empirical standards could theoretically be obtained. This is because the practical constraints of chemical complexity, synthesis challenges, and availability mean that a fully empirical approach is rarely feasible across an entire extractables profile. However, predictive models require at least tentative identification of the compound; complete unknowns still need chemist expertise to establish chemical class before modeling applies. The key is documenting when and why prediction was used and demonstrating that the approach aligns with a risk-based strategy.¹ Stay Ahead of the Curve This blog covers the patterns we see most often. But the full picture — including how predictive modeling works, where it fits in a risk-based strategy, and how to document defensibility for regulators — requires more space than a blog allows. We’ve put together a guide for you that goes deeper on all of this, including the specific changes in ISO 10993-18, the quantification and identification challenges that trip up submissions, and the practical steps to modernize your approach. Download the Guide References1. International Organization for Standardization. (2020). ISO 10993-18:2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process. https://www.iso.org/standard/64750.html2. U.S. Food and Drug Administration. (2023). Use of International Standard ISO 10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and3. Norwood, D.L., Paskiet, D., Ruberto, M., et al. (2006). Best practices for extractables and leachables in orally inhaled and nasal drug products: an overview of the PQRI recommendations. https://pubmed.ncbi.nlm.nih.gov/18183477/4. International Organization for Standardization. (2026). ISO/CD TS 25364-1 Chemical characterization of medical devices — Part 1: Identification of organic extractables in Non-Targeted Analysis (NTA). https://www.iso.org/standard/90930.html5. United States Pharmacopeia. (2023). USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems. https://doi.usp.org/USPNF/USPNF_M7126_03_01.html6. United States Pharmacopeia. (2023). USP <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems. https://doi.usp.org/USPNF/USPNF_M7127_03_01.html #### ISO 14971: 2019: 3 Key Changes from ISO 14971: 2007 As the underlying risk management process for medical devices, the ISO 14971 standard is a critical component of regulatory and quality compliance. When new versions are released and harmonized, it’s up to manufacturers to learn about the changes to update systems accordingly. However, there is often a gap between the time a new version is released and when regulatory organizations require compliance. This is currently the case with ISO 14971:2019, which is not yet harmonized with the new EU MDR and IVDR regulations. Not surprisingly, this has caused some confusion in the industry, especially since some notified bodies are using it as a reference. IVD reclassification under IVDR is also forcing many manufacturers that used to self-certify to show evidence of compliance in their technical documentation. The fact is, if you manufacture medical devices or IVDs in any market, it’s important to understand ISO 14971:2019 requirements.  Overview of ISO 14971:2019 Published by the International Organization for Standardization (ISO), ISO 14971:2019 is the latest version of the standard that describes the application of risk management to medical devices. The standard, which also includes software and IVDs, applies to the entire life cycle of a product and describes processes for identifying hazards, estimating and evaluating the associated risks, and methods for controlling risks and monitoring the effectiveness of those controls.  Risks related to medical devices and IVDs could be associated with: Biocompatibility Data and systems security EMC (electromagnetic compatibility) Moving parts Radiation Usability Manufacturers are expected to use the defined processes to establish objective criteria for acceptable risks and weigh them against the benefits the device provides. The main drivers for updating the standard were to: Align with ISO 13485:2016, MDR, IVDR, and FDA emphasis on post-market surveillance Make ISO 14971 more user-friendly and easier to understand with more guidance on key focus areas Make the standard up-to-date with 21st century medical device technology and the application of software used in medical devices Key Changes with the Release of ISO 14971:2019 Version 14971:2019, which was released in 2019, replaces the prior 2007 version. Although the risk management process is largely the same, there are three significant differences in the versions that manufacturers need to be aware of. 1. Expanded annexes In an effort to simplify the primary document and make the requirements for compliance more clear, guided explanations and expanded dependencies were removed and included as annexes in the technical report (ISO TR 24971:2020). This makes the standard more user-friendly because it is easier to have a high-level view of the requirements. The annexes have been expanded to include more examples and guidance in an effort to make it easier for manufacturers to comply. ISO 14971:2019 has become less bulky and focuses primarily on what you must implement. TR 24971:2020 was updated to create a more user-friendly reference on how to implement clauses into your risk management process. In addition to revamping and moving the annexes to a new document, there were some additions. Annex G was added to cover risk management for cybersecurity. Annex H covers how to assess and remediate risk management files of devices that previously did not comply with ISO 14971. As IVDR reclassified a lot of devices in comparison to the IVD, Annex H is a tool to help get you into compliance. 2. New focus on benefits Although it is still fundamentally a risk management standard, the new version puts more emphasis on the benefits a product delivers relative to the associated risk. The definition of “benefit” is now included in the standard and manufacturers are expected to explain the benefits their devices provide. Examples for how to complete a benefit-risk analysis are helpfully included in the ISO/TR 24971:2020 guidance annex for this new requirement. 3. Post-market requirements The ISO 14971 standard has always applied to the entire life cycle of a device, but the new standard has more requirements for post-market activities. This is one area that had more significant changes and additions to the content, so pay close attention when revamping systems to meet the new requirements. The most significant change is the requirement for more proactive data collection and integration of risk management and quality systems. Now you must not only look reactively at complaints but search the risk management system you use to continuously provide feedback into your post market surveillance system. The standard now aligns more closely with ISO 13485:2016, making it more clear how to integrate your systems, create feedback loops for data, deal with complaint handling, internal auditing, customer feedback, control of nonconforming data, improvements, and data analysis. New information and data collection activities in your post-market surveillance process must be integrated into your risk management process and you must demonstrate how these systems are linked. Challenges with Implementation Although ISO 14971:2019 has been released and is available to manufacturers, it has not yet been harmonized with the EU. However, we have seen that many notified body reviewers are using ISO 14971:2019 as the reference for risk management when evaluating technical documentation under MDR and IVDR. ISO 14971:2019 is indeed the state of the art process for putting risk management procedures in your quality system, which is why it is being referenced even though it has not yet been harmonized. Although we don’t necessarily agree with this approach, it is the current reality and manufacturers have to be prepared for it, especially if they don’t want to get slowed down during notified body review. Consequences of Non-Compliance In the EU, because the standard has not been harmonized, there are no concrete consequences, but as mentioned above, it is the current de facto standard and it behooves manufacturers to comply with it when getting products approved. In the US, manufacturers must show evidence of compliance in their 510(k) submissions and during quality system audits. Non-compliance could result in 483s, audit findings, recalls, removal from the market, and most importantly, risks to patients.  The bottom line is that if you don’t comply with ISO 14971:2019 in the US, you won’t achieve 510(k) clearance. In the EU, the line is fuzzier, but there is a good chance your technical documentation won’t be approved. Next Steps for ISO 14971:2019 Compliance If you are currently compliant with ISO 14971:2007 and EN ISO 14971:2012, you shouldn’t have to make too many changes. Take the time to perform a gap analysis and address any weaknesses that arise. This update was done to harmonize across the IVDR and MDR and therefore will integrate into your post-market surveillance (PMS) plan, periodic safety update reports (PSURs), and your post-market surveillance report (PMSRs). If your device is state of the art, writing the required risk-benefit analysis shouldn’t be too difficult, especially with the new examples provided in the annexes. However, this could be a challenge for legacy devices that have not kept up with the latest technology. If you are new to risk management or now have to submit technical documentation for notified body review under IVDR, you might want to employ outside help from an expert. RQM+ is Here to Help RQM+ has extensive experience in all clinical specialties with updating quality systems to be compliant with ISO 14971:2019 and the MDR/IVDR. We are perfectly positioned to help you create the optimal approach to communication and data transfer between departments and systems. The ideal arrangement is for RQM+ to provide support in all impacted areas—CERs/PERS, post-market surveillance, and risk management—to ensure consistency and efficiency. This process also ultimately benefits the business because it aligns the data and associated documentation that each group creates.  Many of our team members have a medical device development background, so we have deep experience with risk management at every stage in the product life cycle.  Contact us today if you’d like to learn more about the business value RQM+ adds with every project we do. #### Join Live Webinar: Decoding MDCG 2023-7 for MedTech Devices Published in December last year, MDCG 2023-7 clarifies when clinical investigations are not mandatory for Class III and implantable devices. MDCG 2023-7 also shares updated guidelines for when data from equivalent devices may be used in a clinical evaluation under the EU Medical Device Regulation (MDR).  A key takeaway is the requirement for a contract with the manufacturer of the equivalent device is not necessarily required in all circumstances. Understanding this guidance is pivotal for companies looking to determine the best regulatory pathway as they innovate and attempt to maintain their products in the EU market.  To explore these changes and their implications further, we invite you to watch our live show. In it, regulatory and clinical experts unpack what the guidance means for MedTech companies. Chaired by a task force member behind MDCG 2023-7, the session covers everything from detailed interpretations of the EU MDR text to practical applications for products transitioning under MDR.  What You Need to Know  To prepare for the show, here are some key highlights of MDCG 2023-7: When Devices Are Exempt from Clinical Investigations — MDCG 2023-7 outlines the specific cases where Class III and implantable devices can be exempt from clinical investigations. Such exemptions are detailed under four distinct cases — in all cases, sufficient clinical evidence or data is needed: Devices designed by modifications to existing devices already marketed by the same manufacturer; Devices previously placed on the market or put into service under the medical device directives;  Devices for which the manufacturer has a contract with another manufacturer they are claiming equivalence; and  WET devices listed in Article 61(6)(b)​. Hierarchy Levels for Access to Equivalence Data — The guidance emphasizes the need for sufficient access to data to justify claims of equivalence between the device under evaluation and an equivalent device. The guidance outlines different access levels to clinical, technical, and biological data needed to show one device is equivalent to another. These range from having a contract in place or full access to the data to relying solely on publicly available information. Importantly, MDCG 2023-7 specifies that having a contract allowing full access to the technical documentation of the equivalent device is not required in all circumstances. How Documentation and Notified Bodies Factor In — Manufacturers must document their justification for claiming equivalence and exemptions in their Clinical Evaluation Report (CER), which must be accepted by the notified body. This includes detailing the level of access to the equivalent device's technical documentation and how it supports the claims of equivalence or exemption​. How MDCG 2023-7 Can Help You Drive Innovation Embracing and understanding MDCG 2023-7 presents a strategic advantage for companies looking to innovate new and existing products — especially manufacturers offocused on Class III and implantable devices. By clarifying exemptions for clinical investigations and understanding how to leverage data from equivalent devices, the guidance enables companies to more swiftly navigate the approval process. This accelerates the time-to-market for some Class III and implantable devices, ensuring faster patient access to critical healthcare solutions. MDCG 2023-7 also helps ensure that product safety and regulatory compliance are never compromised. By detailing documentation and notified body involvement for equivalence claims, the guidance underscores the commitment to maintaining high quality and safety standards. Unlock the Benefits of MDCG 2023-7 — Reserve Your Spot Today Sign up for our live show for more insights on unlocking the benefits of MDCG 2023-7. You’ll gain strategies to reinforce your clinical data packages and insights on establishing “sufficient access” for equivalence claims. This workshop will also provide tips to help your devices succeed in the EU market.  Don't miss this opportunity to stay ahead in the MedTech industry. Sign up for free access to exclusive and expert insights on MDCG 2023-7. Watch the Show Live Show Panelists Amie Smirthwaite BEng, Ph.D., FRAPS, — Senior Vice President, Scientific Affairs Jaishankar (Jai) Kutty, Ph.D. — Vice President, Intelligence & Innovation Jon Gimbel, Ph.D. — Vice President, Technical Consulting Services Bethany Chung, Ph.D., RAC — Principal Regulatory Scientist #### Key Benefits of Chemical Characterization Laboratory Services Chemical characterization is an integral part of the life sciences industry. It factors into all aspects of pharmaceutical and medical device development, from preclinical research and early risk analysis to post-marketing surveillance of end products. The approach varies, though the methodology largely remains the same. Specialist workflows are used to identify and quantify the chemical constituents of a material or product to assess viability, analyze risks, determine efficacy and safety, support regulatory approvals, and more. This complexity can be challenging to manage, particularly for companies attempting in-house chemical characterization. Here, we will explore some of the pain points associated with in-house testing and suggest solutions based on outsourcing chemical characterization laboratory services. Pain Points 1. Lack of In-House Expertise Chemical characterization requires specialized knowledge and experience. Many companies, especially those with limited R&D budgets, lack the personnel with the necessary expertise. This can lead to inaccurate results, non-compliance, and potential safety issues. Without a team of experienced scientists and technicians, conducting thorough chemical analysis and interpreting complex data is challenging. Outsourcing chemical characterization provides access to teams of experienced scientists and technicians. These professionals specialize in various analytical techniques and have extensive experience with complex materials.  Jordi Labs, an RQM+ company, has over 40 years of experience in polymer systems and is highly regarded for our extractables and leachables (E&L) testing. Our expertise ensures accurate and reliable results, minimizing risks and enhancing product safety. 2. Equipment Costs The analytical equipment required for chemical characterization is expensive. High-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and other advanced instruments represent significant capital investments. For companies with limited budgets, acquiring and maintaining such equipment is often impractical, leading to reliance on outdated or inadequate tools that compromise the quality of analysis. Service providers invest in the latest analytical equipment, ensuring high-quality results and a broad range of testing capabilities. We utilize proprietary, multi-detector approaches and maintain an extensive database for better identification and quantitation. Our advanced tools and methodologies eliminate unknowns and reduce response factor variation, providing more accurate and comprehensive analysis than typically possible in-house. 3. Time Constraints Conducting in-house chemical characterization can be time-consuming. The process demands meticulous sample preparation, analysis, and data interpretation. For companies juggling multiple projects, dedicating time and resources to chemical characterization can detract from other critical business activities, delaying product development and time-to-market. Outsourcing chemical characterization is often more cost-effective than maintaining an in-house lab. Companies can avoid the high costs of purchasing and maintaining advanced analytical equipment. Additionally, outsourcing frees up internal resources, allowing companies to focus on their core competencies and accelerate product development. We offer streamlined processes and dedicated resources, resulting in faster turnaround times and improved efficiency. 4. Regulatory Compliance Regulatory requirements for chemical characterization are stringent and vary across regions. Ensuring compliance with standards set by bodies such as the FDA, ISO, and AAMI requires a deep understanding and continuous monitoring of regulatory changes. Without proper expertise, companies risk non-compliance, which can lead to costly delays, fines, and potential product recalls. Service providers are well-versed in regulatory requirements and ensure that testing complies with relevant standards. We lead in developing and improving standards as members of AAMI and ISO committees. We also offer extensive support for regulatory submissions, helping companies navigate pre-submission and submission issues with the FDA and other notified bodies. Other Benefits of Outsourcing 1. Flexible Service Options Outsourcing provides flexibility with customizable testing packages tailored to meet specific client needs. Whether for one-off projects or ongoing support, service providers can adapt to varying demands. We offer a comprehensive suite of services, from biological evaluation and toxicological risk assessments to material characterization and polymer analysis, catering to diverse industry requirements. 2. Faster Turnaround Times With dedicated resources and streamlined processes, service providers can often deliver results more quickly than in-house labs. We leverage our expertise and advanced methodologies to provide timely and accurate results, reducing the time-to-market for new products and ensuring compliance with regulatory timelines. Interested in Laboratory Services? Outsourcing chemical characterization laboratory services offers numerous benefits, from access to specialized expertise and state-of-the-art equipment to cost savings and regulatory compliance. By addressing the pain points associated with in-house characterization, companies can enhance their product development processes, ensure safety and efficacy, and remain competitive in their respective industries. Partnering with a reputable service provider like us at Jordi Labs, an RQM+ company, can significantly improve the quality and efficiency of chemical characterization, driving innovation and success. Read the blog 👉 "New FDA Dataset Marks a Transformative Leap for Chemical Characterization" #### Laboratory Developed Tests: Current State of Play FAQ The uncertainty in the future of LDTs cannot be overstated; there are any number of things that can happen over the course of the next months and years, leaving laboratories in a very uncertain environment. The lawsuits against FDA by American Clinical Laboratory Association (ACLA) and Association of American Pathologists (AMP), the outcome of the election, and the potential for congressional action all have the potential to impact regulations for LDTs. Some key considerations and potential outcomes are outlined in this set of frequently asked questions. Q1: When will we have an answer about the lawsuit? The court has asked for all briefs related to the suit to be submitted by the end of 2024, so we will not see an answer before next year. Legal experts have speculated that a judgement is likely by the end of Q1 2025. This would be only a few months from the first deadline of the final rule (May 6, 2025). Q2: What happens if ACLA/AMP win their lawsuit? This question seems like it should have a straightforward answer, but in reality, there are a few different possibilities. The ACLA and AMP lawsuits all have several different arguments and how each argument is deciphered by the judge could change the impact of the outcome. For example, the court could rule that LDTs are not IVDs. This result would essentially halt the final rule and make FDA action on LDTs impossible without Congressional action. Alternately, the ruling could rule in favor of the ACLA and AMP but for a different reason, such as that the cost impact is too high for FDA to move forward. In this case, the court has not stated whether FDA has authority to regulate LDTs but strikes down the rule for other reasons leaving the door open for FDA to regulate through a similar path in the future. The industry will have to react to the judgement and the specific language, once it is issued. Q3: What happens if FDA wins their lawsuit? If FDA wins the lawsuit, the final rule moves forward as it is published with the first deadline being May 6, 2025. This ruling could leave laboratories who waited to start LDT transition planning in a very tough position, with little time to make the necessary changes to meet the phase 1 requirements. Q4: What if the lawsuit isn’t resolved before May 6, 2025 or the decision is appealed? Everybody’s favorite answer: it depends! At this point, neither AMP or ACLA has asked for an injunction on the final rule, which would prevent FDA from moving forward with implementation. So, if the summary judgement is still pending, as it stands today the final rule will move forward and the phase 1 deadline will stand. It is also possible that the injunction will be requested as the deadline approaches. If FDA wins the lawsuit, the ACLA/AMP can appeal the decision, but the rule would move forward with phase 1 deadline. AMP/ACLA may request an injunction as the appeal plays out in court. If AMP/ACLA win the lawsuit, the final rule will be halted and the phase 1 deadline will not apply. FDA may or may not seek an appeal but regardless the requirements for phase 1 would not apply in May 2025. Q5: What about the election? The election could have a potentially large impact on the future of the LDT final rule, as the agency leadership is typically replaced when the President changes. With Joe Biden not pursuing reelection, we will see a new President in 2025. Depending on who is elected, and who is subsequently appointed to lead FDA, FDA may take a step back from enforcing the rule or pursuing appeals on the lawsuit if they lose. Q6: Will we see the return of the VALID act? The VALID Act has seen a resurgence in Congress, with a new 2024 version currently being circulated. The contents of this new version are not public but it is clear that Congress is taking some action towards legislation. We may see this effort come back into play as the lawsuit unfurls, but the timeline for congressional action is quite long so it is not expected that new legislation will be passed before the lawsuit judgement or the phase 1 deadline. Q7: What should laboratories be doing? If anything is certain for the LDTs today it is that nothing is certain. Laboratories should take a conservative approach to ensure that they remain in compliance and do not phase any consequences of being ill-prepared should the final rule move forward. RQM+ recommends two specific activities for laboratories to complete in 2024, and can help support organizations in these efforts: Assess your test menu, understand how the final rule applies to your organization, and document your approach for compliance. Understand the changes that are required for phase 1. It is imperative that organizations do not wait until the lawsuit is concluded to start this process as there will not be enough time to implement all of the requirements ahead of the deadline. Still have questions? Connect with us on LinkedIn or contact us directly. Our RQM+ experts are developing more resources to support your LDT transition. Sign up for our IVD IntelHub Newsletter for quarterly updates on all things IVDs! Watch now ▶ MDR and IVDR Amendments: Strategies for Supply Interruption Compliance #### Latex and DEHP and BPA, Oh my! They’re just as frightening as Lions and Tigers and Bears, but how much do you know about them? Are they in your medical devices? Latex There are two different “flavors” of latex: natural rubber latex and synthetic latex. Natural rubber latex is manufactured from a milky fluid that is primarily obtained from the rubber tree (Heva brasiliensis). Natural rubber proteins are what are responsible for allergic reactions in some people. Synthetic latex is not usually associated with allergies. [1] Therefore, natural rubber latex is the one the FDA is generally concerned with. According to 21 CFR 801.437, any medical devices that contain natural rubber latex and come into contact with humans must be appropriately labeled to warn the user of possible allergic reactions. [2] This regulation does not forbid you from having latex in your products, but it is intended to protect the public health by providing adequate information to the users of possible risks of use. DEHP Di-(2-ethylexyl) phthalate (DEHP) is a placsticizer (softener) that is commonly added to plastics (such as polyvinyl chloride, PVC) to make them more flexible. Plastics are used throughout the medical device industry, and as you can imagine, so are plasticizers. Since plasticizers are not chemically linked to the plastic, over time they can leach out of the plastic into solutions. [3] DEHP exposure has shown negative effects in animal models, particularly on the male reproductive system. While human exposure levels and adverse effects have not been well defined, the industry recognizes DEHP as a risk that can be averted by limiting the exposure of patients to DEHP. Manufacturers can assist in mitigating risk of DEHP exposure by designing devices with alternative materials (such as ethylene vinyl acetate, silicone, polyethylene, or polyurethane). [3] BPA Bispheonol A (BPA) is a chemical that is used to manufacturer polymers, mainly polycarbonate polymers and epoxy-based enamels and coatings. Since polymeric reactions do not go entirely to completion, small residual amounts of BPA can remain in polymers and leach out over time. BPA can be found in hard plastic bottles and containers, and has mainly been of concern in food contacting products such as Tupperware, baby bottles, and linings of cans [4]. Much like DEHP, the there is no consensus on the health effects of BPA. There have been studies that suggest exposure to BPA can lead to reproductive and developmental issues, with fetuses, infants, and young children being the highest risk populations [4]. In the medical device industry, BPA exposure risk is probably highest in pediatric patients who undergo cardiopulmonary bypass, and dialysis patients [5]. For one reason or another, many manufacturers have chosen to eliminate these materials from their products. Some have done it to mitigate potential risks to public health, while others have done it to gain a marketing advantage over their competitors. There are a lot of important things to think about when choosing your materials. Despite the controversies, if you have the opportunity to eliminate a potential risk by choosing materials that do not contain natural rubber latex, DEHP, or BPA, then I would go for it! - Sherri [1] Latex Allergy; OSHA; 25 Sep 2008; http://www.osha.gov/SLTC/latexallergy/index.html [2] 21 CFR 821.437 User labeling for devices that contain natural rubber; 1 April 2012; http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=801.437 [3] FDA Public Health Notification: PVC Devices Containing the Plasticizer DEHP; 12 July 2002; http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062182.htm [4] Bisphenol A (BPA): Use in Food Contact Application; March 30, 2012; http://www.fda.gov/newsevents/publichealthfocus/ucm064437.htm [5] FDA to Test BPA Exposure from Medical Devices; E Walker; 26 Feb 2009; Washington Watch; http://www.medpagetoday.com/Washington-Watch/Washington-Watch/13022 #### Let's Talk About Women's Health: Diabetes Welcome to our blog series, "Let's Talk About Women's Health." This series is dedicated to sharing powerful patient impact stories, highlighting the real-life experiences of women navigating various health challenges. Our goal is to raise awareness, foster meaningful dialogue, and shine a light on the key challenges and opportunities in MedTech for women's health. In this first installment, Meghann Peters, Human Resources Manager at RQM+, shares her personal journey of type 1 diabetes and her appreciation for the MedTech industry and its transformative impact on healthcare. Stay tuned for more inspiring stories and insights in our ongoing series. Together, we can make women's health happen. Let's Talk About Women's Health: Diabetes Two years ago, my world shifted when I was diagnosed with type 1 diabetes. It came after I’d been experiencing several troubling symptoms that, though alarming, didn’t exactly take me by surprise. You see, my father had lived with type 1 diabetes since he was five years old, and his journey had taught me a lot about the realities of the disease. When my father was diagnosed back in the mid-60s, the tools available for managing type 1 diabetes were basic at best. He was given an insulin syringe and a manual glucose monitor, and the general advice was to cut out all carbs. It was a much more difficult, less informed time for diabetics, and without the technology and support we have today, he struggled to manage his condition. Sadly, my father passed away at the age of 41 due to complications from mismanaged diabetes. His story is one that reminds me of how much has changed—and how much more we still have to learn. Fast forward to 2023, and I find myself in the same boat. However, when I left the hospital, my experience was very different. Instead of just a syringe and a glucose monitor, I left with an automated insulin delivery system and a continuous glucose monitor (CGM). These tools have completely changed the game, making the management of my diabetes much easier and much more precise. With the advancements in technology, what once felt like an overwhelming challenge is now more manageable. The progression in diabetes care is a testament to how far we've come in just a few decades. What my father experienced compared to my own journey shows the growth and advancement of medical technology. Though our experiences are different, the underlying message is the same: living with type 1 diabetes is tough, but with the right tools and the right mindset, it's a challenge we can overcome. Through my personal journey with type 1 diabetes, I’ve gained a profound appreciation for the MedTech industry and its transformative impact on healthcare. Having witnessed my father’s struggles with limited resources and basic tools in the 60s through the early 2000s, and then experiencing advancements firsthand in 2023, I have a unique perspective on how far we've come. The automated insulin delivery system and continuous glucose monitor (CGM) I now rely on have made managing my diabetes significantly easier and more precise, something that would have been unimaginable in the past. These technological advancements not only improve my quality of life but also highlight the importance of innovation and research in the MedTech field. The ability to manage my condition with such sophisticated tools reflects the tireless work of engineers, scientists, and medical professionals dedicated to improving patient outcomes. What once was a challenging and sometimes dangerous condition is now more manageable, and this progress has given me hope for the future. My experience has shown me just how vital the MedTech industry is in shaping the lives of people living with chronic conditions, and I am deeply grateful for the innovations that have made my journey more manageable and empowered. Stay connected with us! Subscribe to our blog to receive the latest updates and insights from our "We Make Women's Health Happen" campaign. Don't miss out on inspiring stories and valuable information on women's health. For another in this series Let’s Talk About Women’s Health: Thyroid Dysfunction. #### Let's Talk About Women's Health: Thyroid Dysfunction Welcome back to our blog series, "Let's Talk About Women's Health." This series is dedicated to sharing powerful patient impact stories, highlighting the real-life experiences of women navigating various health challenges. Our goal is to raise awareness, foster meaningful dialogue, and shine a light on the key challenges and opportunities in MedTech for women's health. In this second installment, Victoria Chester Rose, Vice President, Marketing & Communications at RQM+, shares her personal journey with hypothyroidism. Stay tuned for more inspiring stories and insights in our ongoing series. Together, we can make women's health happen. When ‘Normal’ Isn’t Normal: Advocating for My Health. This is my personal journey. For as long as I can remember, I took pride in taking care of myself by staying active, eating well, and ensuring my overall health was a priority. But somewhere along the way, I started noticing that the little things that once came easily became increasingly difficult. The exhaustion was more than just tiredness after a long day - it was fatigue that persisted even after a full night of sleep. As I continued to struggle with my energy levels, I found myself unable to keep up with my active life. My mind felt foggy, my joints ached, and the weight gain felt unexplained and unstoppable. I knew something wasn’t right. It’s almost as if a light switch had been flipped off and the old me suddenly changed. A Two-Year Journey to Take Back My Health With a family history of thyroid disease, I knew I needed to have my thyroid tested. Each time, my TSH (thyroid-stimulating hormone) levels were at the high end of the “normal” range, but still within what was considered acceptable. This went on for two years—two years of feeling unlike myself, two years of advocating for my health while being told that I was still within normal limits. It wasn’t until my TSH spiked well into the high range that my doctor finally prescribed medication.But why did it have to get to that point? Why did I have to wait until my numbers were “bad enough” for treatment, despite experiencing all the hallmark symptoms of hypothyroidism? The Mental and Physical Toll Physically, I felt like I was trapped in someone else’s body. It slowed me down in ways I never expected, and the simplest tasks required an immense amount of energy. Perhaps the most challenging part was the mental toll. The frustration of knowing something was wrong yet not having it validated was exhausting. The constant battle of trying to push through my symptoms while hearing advice like, “eat more protein, move more, maybe you’re taking on too much,” was beyond defeating. Too often, women’s health symptoms are dismissed as stress-related, hormonal, or just part of aging. We are told to get more sleep, to exercise more, or to simply “manage our stress better.” What happens when we do all of that and still don’t feel right? The answer shouldn’t be to suffer in silence or wait for our condition to become severe enough to warrant intervention. The Importance of Advocacy in Women’s Health My entire career has been spent in healthcare and I know firsthand the gaps in women’s health. I have seen how often we are overlooked, our symptoms minimized, and our concerns dismissed. I also know I’m not alone in this experience. It’s why I will continue to shine a light on women’s health. Being your own advocate in healthcare can be frustrating and exhausting, yet very necessary. Remember, you are not just a number on a lab report, a symptom or a statistic. If something feels off, push for answers. Challenge your doctors, ask for further testing, and don’t settle for “it’s probably just stress.” You know your body better than anyone! The Role of MedTech in Advancing Thyroid Health Thankfully, advancements in MedTech are changing the way we diagnose and manage thyroid disease and RQM+ is at the forefront of laboratory-developed tests (LDTs), providing expert guidance to ensure these innovative diagnostic tools meet regulatory requirements while delivering precise and personalized results. LDTs are enabling earlier and more accurate detection of thyroid dysfunction, allowing patients to receive the right treatment before their symptoms become debilitating. I’m proud to be part of an organization that leads in this space. Why Believing in Yourself Matters I believe being a patient first makes me better at my job! I am proud to work for a company that prioritizes women’s health and embraces the latest innovations to improve care and outcomes. If you’re experiencing symptoms that don’t feel right, don’t let them be dismissed. Keep asking questions, keep pushing for answers, and most importantly, advocate for yourself. Your health is worth fighting for. Join us on Thursday the 20th of March, 2025  for our women's health panel, "Built for Her: Funding, fixing, and fueling the next era of MedTech." In this RQM+ Live! panel discussion, industry leaders and regulatory experts will share real-world strategies MedTech companies can use to navigate the landscape. For more on a similar topic - Addressing Unmet Needs in Women's Health: Devices for Mental Health Support #### Mastering the Transition: 5 Essential Tips for EU MDR Compliance Introduction Regulation 2023/607 removed the May 2024 transition deadline for medical devices transitioning from MDD/AIMDD to MDR 2017/745. The end of the transition period was pushed back to 2026, 2027 or 2028, depending on the classification of the device. The collective sigh of relief amongst many device manufacturers could be heard from Athens to Zaragosa! An extension of 3 ½ or 4 ½ years for the majority of transitioning legacy devices sounds great, but that time needs to be used wisely, and there are a couple of earlier deadlines that need to be met in order to make use of the extensions. We’ve picked out the key dates and considerations for legacy device manufacturers in this blog post. For even more insights and directly from notified body BSI, sign up for our RQM+ Live! show on 27 July 2023, where BSI’s Head of Clinical Compliance, Richard Holborow, will join us to provide a notified body’s view on the latest best practices for MDR compliance. Here's the link to register. View Webinar with BSI's Richard Holborow 1. Step back and reassess The amendments to the transitional period brought about by Regulation 2023/607 may have opened some doors that were previously thought shut. CE Certificates that were valid on 26 May 2021 but expired before 20 March 2023 have a new lease of life if there was a signed agreement with a Notified Body for a MDR conformity assessment. The introduction of the ‘substitute device’ concept may also reinvigorate plans for legacy devices that are due to be replaced by new design iterations. Remember... Plans are living documents that should be revisited and updated in light of new information. 2. Know your dates Whilst you may keep your Class IIa device on the EU market up until 31 Dec 2028 under these new transitional arrangements, it does not come for free. There are two key dates that form part of the conditions for the extended transitional arrangements. If the requirements have not been fulfilled by these two dates, MDD/AIMDD CE certificates (see also self-declarations for those devices up-classified under MDR 2017/745) will not be valid. Ensure that you: Assess your QMS against Annex ZA of EN ISO 13485:2016 / A11:2021. Incorporate the QMS requirements of MDR 2017/745 into your internal audit schedules and plans. Assess your procedures and infrastructure so that you can readily support hybrid audits to give you more flexibility with scheduling. Both the MDCG and Team NB have produced position papers on the use of hybrid audits. Liaise with your, existing or new, notified body to understand what you need to provide as part of their application process. 3. Certificates please! Knowing what the amendment to the regulation says is one thing, but proving your legacy device can legally remain on the market when your CE certificate appears to have expired is another. There will be no new certificates with new expiry dates issued by notified bodies under the MDD/AIMDD, as the extension of a certificate’s validity is done automatically by law as long as the conditions for extension are fulfilled. The simplest way to demonstrate the extended validity (e.g. to customers) is via a self-declaration; confirming that you fulfil the conditions and requirements of MDR 2017/745 Article 120(3) (as it was amended by Regulation 2023/607). Fortunately, MedTech Europe, COCIR and others have produced a template for legacy device manufacturers to use: Manufacturer’s declaration in relation to Regulation (EU) 2023/607. This self-declaration also acts like a checklist of what you, as a manufacturer of legacy devices, need to do in order to make use of the extended transitional period. Additionally, you can support your self-declaration with a confirmation letter from your notified body (i.e. the notified body who will be conducting your conformity assessment under MDR 2017/745). This confirmation letter covers the scope of your certificate(s) and the content needs to be verified by your notified body. Be advised: this confirmation letter takes time to prepare and is unlikely to be produced within days of your request. Ensure that you: Identify and include all of the relevant devices and codes in the scope of your self-declaration (and notified body confirmation letter). Accidental omissions from these documents may prevent efficient sales to new customers or registrations in other markets. 4. Get your documents in order Once your contract is in place with your notified body, you can schedule the assessment of your technical documentation. One new addition to the process is the notified body completeness check, performed by ~81% of the Team NB members (Team NB, Medical Device Survey 2022). The 2022 survey data presented by Team NB indicates that the submissions were significantly lacking in the required content (i.e. as per Annexes II and III of MDR 2017/745), i.e. 80% of those notified bodies performing the checks reported that technical documentation was only 50% complete or less. This tallies with the opening remarks in the Team NB best practice for MDR technical documentation. In that guidance, Team NB state the most common reasons for delays in the reviews are due to incomplete submissions (required evidence not provided) and/or the lack of a cohesive structure (evidence is provided, but is not easy for the reviewer to locate). Anecdotally, delays in reviews are being seen where manufacturers are unprepared for answering the reviewers questions, and so new evidence needs to be prepared rather than supplying existing objective evidence. Consider: Familiarizing yourself with the Team NB guidance and the applicable MDCG guidance. While these are not mandatory, they provide the insight into what the notified body reviewer(s) will be looking for in your evidence. Assessing your technical documentation thoroughly before submitting to your notified body; preferably use an independent reviewer, i.e. outside of the specific project team (either internal or external). The questions you may be asked by your reviewer and be ready to provide that information (e.g. up to date post market surveillance data, evidence of active risk management activities). 5. Time is on whose side? The 3 ½ or 4 ½ year extensions for the validity of legacy device CE certificates are intended to help notified bodies get through the required conformity assessments. It was not primarily intended to give device manufacturers more time to compile their evidence for compliance to MDR 2017/745. The contract with your notified body needs to be in place by 26 September 2024. By that point, you need to be clear with your notified body when your technical documentation and QMS will be ready and available for the conformity assessment. The data presented by Team NB indicates that notified body reviews of technical documentation under MDR 2017/745 are mostly taking up to 18 months. That does not necessarily mean that the review can safely take place in 2026 or 2027 in order to be complete before the 2027 or 2028 deadlines, respectively. Throughout the transition period and up until the CE certificate is issued under MDR 2017/745, your legacy device is restricted. There can be no significant changes in the design or intended purpose of the device, otherwise, it invalidates the extended validity of the MDD/AIMDD CE certificates. Manufacturers who successfully transition to CE marking under MDR 2017/745 earlier are in the position to make changes (still under the oversight of the notified body’s conformity assessment) to respond to changing market needs, customer requirements or technological advances when compared to manufacturers making full use of the extended validity of the MDD/AIMDD CE certificates. Ensure that: The criteria for significant changes, as per MDCG 2020-3 Rev.1, are embedded in your change management processes. Planned changes are evaluated alongside your regulatory strategy and the timeline for review provided by your notified body. Want to know more? View Webinar with BSI's Richard Holborow Sign up for our RQM+ Live! show on 27 July 2023 where BSI’s Head of Clinical Compliance, Richard Holborow, will be joining us to provide a notified body’s view on best practices for MDR compliance, including tips for manufacturers of legacy devices transitioning to the MDR. If you're reading this and the date of the show has passed, please know it's available on demand at the link. If this post has helped you realized or otherwise inspired you to seek support at your organization, please contact RQM+ for any needs related to QMS implementation, independent QMS audits, compilation and/or remediation of technical documentation, pre-submission assessments of technical documentation, responding to notified body review questions and/or planning of post-market activities to gather more evidence. #### Med Device Monday - Luminopia One, A Digital Therapeutic to Help Treat Amblyopia In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  Last week, FDA’s announcement of the most recently granted De Novo Request landed in our inbox thanks to the CDRH free email alerts (don’t get these yet? sign up HERE!). We were excited to see that on October 20, 2021, FDA concluded that Luminopia One is a Class II medical device for which class II (special) controls provide reasonable assurance of the new device’s safety and effectiveness.As part of the De Novo process for Luminopia One, FDA generated a new regulation (21 CFR 886.5500) and defined the generic name for the regulation as “digital therapy device for amblyopia”. Amblyopi-wha? Let us explain…Amblyopia is commonly known as lazy eye, and it is a disorder in which the brain fails to process inputs from one eye. As a result, the part of the brain receiving images from the affected eye is not stimulated properly and does not develop to its full potential. If amblyopia is not detected and treated early in children, the decreased vision can become permanent.People will often misuse the term ‘lazy eye’ when referring to an eye that crosses or turns outward, but this is actually strabismus, a neuromuscular condition where one eye is turned in a direction that is different from the other eye. While strabismus can be a cause of amblyopia, strabismus is just one of several conditions that can lead to a lazy eye and the visual centers in the brain being underdeveloped.Amblyopia can be difficult to detect because children are often unaware that their visual experience is unlike that of others. A lazy eye is often diagnosed during a routine eye test before parents even realize there is an issue. Once detected, treatment of amblyopia depends on the condition’s cause. If there's a problem with the amount of light entering the eye, such as a cataract blocking the pathway of light, treatment will be needed to remove the blockage. If there's an eyesight problem such as near-sightedness, glasses may be used to correct the focus of the eye. At this point, the child is encouraged to use the affected eye, either through the use of an eye patch to cover the stronger eye, or the use of eye drops to temporarily blur the vision in the stronger eye.The introduction of Luminopia One provides a new treatment option for children 4-7 years old with amblyopia. The device is a software-only digital therapeutic designed to be used with commercially available Head-Mounted Displays…think virtual reality goggles. Rather than having to wear an eye patch every day for years, kids watch TV and movie content that is presented to each eye differently via a kid-friendly headset. On their website, Luminopia Inc. states, “Thanks to powerful neural plasticity, this rebalancing approach strengthens visual processing, promotes weaker eye usage, and encourages both eyes to work together properly!”We at AcKnowledge RS are particularly excited about this new device. Not only will Luminopia One be a welcome alternative for families who struggle to get their child to wear their eye patch, we anticipate patient compliance is going to be excellent! We’re pretty sure most kids will happily endure an hour of screen time every day in the name of improved eyesight! Technology for the win!Further Reading Luminopia Inc. Luminopia One Classification Order De Novo Classification Request CDRH Mailing Lists Learn More About Amblyopia Med Device Monday: Bone Anchors Med Device Monday: Nonabsorbent Dressing #### Med Device Monday: Bone Anchors In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  FDA has just released a draft guidance for bone anchors. This new draft guidance document, dated January 3, 2017, is a reissuance of the previous version from April, 1996: "Specifically, this guidance reflects the most current thinking on relevant bench testing methods for bone anchor devices including nitinol and absorbable polymeric bone anchors."  Bone anchors! These cool medical devices help attach soft tissue to bone. Partial or full detachment from the bone of ligaments, tendons and other tissues, are common injuries. Think achilles tendons, rotator cuff tears and other shoulder injuries, ACL tears and other knee injuries, and countless other ailments. While these tissues can re-attach without intervention, in some cases, especially with complete detachment, surgery may be necessary to help the process along. Bone anchors assist with these surgeries by, literally, anchoring a suture to the bone from the tissue. The injury will then heal as the as the connection between bone and tissue is reestablished. Have a look: This video provides a pretty cool illustration of how it works: //www.youtube.com/embed/CGAySiMqu_Q?wmode=opaque&enablejsapi=1 And this video provides a different angle and shows a different type of anchor: //www.youtube.com/embed/dHkEqmEC-2A?wmode=opaque&enablejsapi=1 Some of these anchors, like some of the sutures they help affix, are dissolvable. It's always impressive to encounter a device that can do its job and then quietly disappear. The new draft guidance focuses on this area, and the Office of the Federal Register explains, "The guidance provides recommendations for the information and testing that should be included in premarket submissions for bone anchor (suture anchor) devices used in the appendicular skeleton for attachment of soft tissue to bone. This draft guidance is not final nor is it in effect at this time."  Comments are being accepted through March 6, 2017, and the link above to the Federal Register explains how they can be submitted. Further reading: Code of Federal Regulations for single/multiple component metallic bone fixation appliances and accessories Corresponding MAI product code Code of Federal Regulations for smooth or threaded metallic bone fixation fastener Corresponding MBI product code #### Med Device Monday: Briteseed and SafeSnips In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  In September, Med Device Monday featured cool medical devices that have not yet been FDA approved. I want to squeeze in one last one as we move into October! I've written before about why I do what I do and why it's important to me to get innovative devices like these to market. Products like this are integral to my work, but moreover, they are interesting, innovative, and fill a need. Join me in exploring some exciting new devices that I hope to see on the market soon. Feel free to share more innovative devices in the comments! Briteseed's product is SafeSnips, a device that helps surgeons detect blood vessels before they can accidentally be cut.  In laproscopic surgeries, tools are all the surgeon has. They aren't able to use their tactile senses to detect a blood vessel, and bleeding is a real concern. While estimates are that only 2% of surgical patients have a blood vessel cut accidentally, the founders of Briteseed say that 20% of those who do will die. The SafeSnips Twitter bio says its "technology adds real-time vessel detection to existing surgical tools to improve patients' lives and reduce hospital costs". The Briteseed/SafeSnips website elaborates on the need for this device, saying "Surgeries are inherently dangerous procedures. Regardless of the expertise of the surgeon, a patient who undergoes a surgical procedure is subject to unintended complications that could result in a long recovery time, serious injury, or worse. Despite improvements in surgical technique, unintended cuts followed by bleeding remains a significant risk. In the United States alone, up to 32% of all unintended bleeding incidents are fatal. Patients who do survive face long-term complications that include lengthy hospital stays and decreased quality of life. SafeSnips addresses the need for improved patient safety and better surgical outcomes by working to stop accidental cuts before they happen." So what exactly does SafeSnips do to help? SafeSnips is infrared technology that's intended to be added to surgical tools, and uses infrared technology to detect hemoglobin. This article from Techli sums it up nicely: "How do near-infrared rays come into play? The key lies in hemoglobin, an iron-containing and oxygen-transporting protein in our red blood cells. Incidentally, according to Fehrenbacher, “this hemoglobin absorbs near-infrared rays more than surrounding tissue. Using a novel algorithm, this absorption difference can be used to provide surgeons with the location of blood vessels while using surgical cutting instruments.” And because hemoglobin flows freely throughout the blood vessel, detecting its presence allows for diameter and orientation measurements of the blood vessels, too, as well as how fast the blood flows. According to the SafeSnips website, the detection system is fully automatic and continous, thus adding to the surgeon’s (and patient’s) peace of mind." MedTech Innovator has another video and more information here. More Med Device Monday - Med Device Monday: C-Section Retractor #### Med Device Monday: C-Section Retractor In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  When operating in the abdomen via direct incision (as opposed to laparoscopically), it can be a challenge to get adequate and clear access to the area being worked on. For C-sections in particular, the challenges of getting direct and clear access to the uterus are several.  Some physicians prefer to move the uterus outside the incision to work on it exteriorly to ensure accessibility. Babies are often born this way, and the uterus is then sutured and returned into the abdominal cavity. This presents it's own challenges, such as nausea and vomiting in the patient. For physicians who may want some additional help with in situ (within the abdominal cavity) repair—or even because they want to avoid extra-abdominal uterine work—the Alexis C-section Retractor may be a useful tool. Approved by FDA in 2006, the Alexis C-Section Retractor is a disposable, single-use medical device that helps facilitate in situ uterine procedures—specifically C-sections—by allowing the uterus to remain in the body and providing clear access to it by aiding in retraction. It comes in two sizes to accommodate different anatomies and incisions. One ring is inserted into the incision and placed around the uterus. The external ring is then rolled down to increase tension, retract the wound, and open up the area for surgical access. This video illustrates it well (it does show a full C-section birth, so fair warning): Click to watch video. (WARNING: This video may be inappropriate for some users.) It's worth noting that there are conflicting opinions about whether it is best to operate on the uterus in situ or extra-abdonminally (exteriorly). To that end, a 2008 NCBI randomized controlled trial determined that "there is no significant difference between extra-abdominal and intra-abdominal repair of the uterine incision at cesarean delivery, but the number of sutures is lower and surgical time is shorter with extra-abdominal repair, although moderate and severe pain at 6 hours is less frequent with in situ uterine repair". Ultimately, the Alexis Retractor is a device that provides options. I imagine some surgeons will have their procedures comfortably down pat and don't feel they need an extra set of (proverbial) hands, while some will embrace the opportunity for the extra help. Further reading: Alexis wound retractor 510(k) summary NCBI evaluation of the Alexis Retractor (An interesting read.) Med Device Monday – Luminopia One, A Digital Therapeutic to Help Treat Amblyopia #### Med Device Monday: Nonabsorbent Dressing In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  Nonabsorbent dressing! No, that's not the name of a band or a gravy-resistant Thanksgiving side dish. In the medical field, the term is usually "adsorbent", and that's exactly what D2 QuikClot internal bandages are.  QuikClot bandages from Z-Medica have been on the market for some time. They look like regular gauze bandages in various sizes, shapes, and packages, but they are "coated or impregnated" with kaolin, a clay (natural or made in a lab) that can help induce clotting. The bandages are meant not to soak up blood (though they will do that too), but to actively stimulate clotting. Once the patient has been stabilized, the bandage is to be removed.  The implications for a product like this are far-reaching. Field sites, remote and rural places, military operations, and even for injuries that happen close to medical facilities but which might be severe. Z-Medica recently gained de novo approval for what is essentially a new version of this device. Dubbed QuikClot Control+, these bandages are, per Z-Medica  "...the first and only non-absorbable hemostatic dressing cleared for internal organ space use in severely bleeding patients. QuikClot Control+ is indicated for temporary control of internal organ space bleeding for patients displaying class III or class IV bleeding. It may also be used for control of severely bleeding wounds such as surgical wounds and traumatic injuries." These bandages are a version of the regular QuikClot that are approved to be used internally. Some might even say they are substantially equivalent! (That's a de novo joke, and not a very good one.). Like their original counterpart, they also look like guaze bandages, and have that same clot-inducing material in them to help stop bleeding with a quickness. The difference here is that they are approved for major bleeding, trauma, and to help with internal injuries. Class III and Class IV bleeding are classifications of hemorrhage-level bleeding. Class III indicates a loss of 30-40% of circulating blood, while Class IV is 40% or more. A bandage that can stop that type of severe blood loss is pretty impressive. What's also interesting about this de novo approval is the testing that was required. First, this product was tested only on animals. That might not be the most pleasant thing to think about, but you don't exactly want to wait and test it out on a human patient who's bleeding out in front of you.  Second, check out this list of considerations and factors to prove when getting FDA approval for a device that, on its face, seems relatively simple: In other words: is this product going to work? Will it cause infection if the sterility isn't maintained? Will it have a negative impact on the surrounding tissues? Will it create complications down the road? Will the patient get an embolism or bleed out later anyway? FDA wants to know what the risks are for your device and then understand how you have mitigated these risks to make it safe and effective.   This is another good example of a medical device that seems so simple and straightforward—and to some degree it is, as it was granted de novo approval—but which showcases the rigor and thorough thoughtfulness required to get a medical device through FDA! Further Reading: de novo approval Device classification Devices for the Military Med Device Monday: Briteseed and SafeSnips Med Device Monday: Restless Leg Relaxer #### Med Device Monday: Restless Leg Relaxer In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  Restless Leg Syndrome (RLS) is a neurological sensorimotor condition that affects around 1 in 10 Americans. Also known as Willis-Ekbom Disease, symptoms largely include an uncontrollable urge to move the legs, which can disrupt sleep for sufferers.  According to the National Sleep Foundation, the disorder is "characterized by an overwhelming urge to move the legs when they are at rest. The urge to move the legs is usually, but not always, accompanied by unpleasant sensations. It is less common but possible to have RLS symptoms in the arms, face, torso, and genital region. RLS symptoms occur during inactivity and they are temporarily relieved by movement or pressure. Symptoms of RLS are most severe in the evening and nighttime hours and can profoundly disrupt a patient's sleep and daily life." There is no cure for RLS, but thanks to Relaxis, there is now a non-medical treatment that eases discomfort and helps patients sleep. According to the Relaxis website (formerly Symphony, as you will see in the FDA clearance docs), their founder suffers from RLS: "He found relief from his RLS symptoms by getting out of bed, standing and walking. Although his symptoms were gone, the physical act of standing or walking left him wide awake. Dr. Burbank postulated that a device providing counterstimulation, while in bed, would relieve his symptoms and allow him to quickly return to sleep. As a result, our team developed a series of test devices and found that these devices allowed him to remain in bed while relieving his symptoms." They go on to explain that Relaxis is a "Vibratory counter-stimulation device. A vibratory counter-stimulation device is a prescription device that provides electrically powered mechanical vibration to improve the quality of sleep in patients with primary Restless Legs Syndrome."  Sleep deprivation isn't just tiring: it can be life-threatening. Chronic sleep deprivation can lead to accidents & injury, obesity, heart disease, depression, suicide, kidney disease, diabetes, stroke, and more. (Also discussed this in a previous post about an insomnia device.) Any device that provides relief to patients and leads to more and improved sleep is certainly a win. Further reading: Relaxis/Symphony Classification Order Relaxis/Symphony Decision Summary #### Medical Devices, IVDs and Other EU Laws By Chris A. Parr - Principal, CRO As a follow up to the “Recent developments in EU Horizontal Legislation” blog, we will now take a deeper dive into the multi-legislative compliance process for medical devices and in-vitro diagnostic medical devices (IVDs). Building on what we learned in the first instalment about product safety legislation and horizontal legislation, we will look at what it takes manufacturers to comply with sectorial, horizontal and national regulations. Applicable Harmonisation (Sectorial) Legislation   Since the publication of the medical device regulation (MDR) and the IVD regulation (IVDR) in 2017 there has been a profound change in how medical devices and IVDs are regulated in the EU. Manufacturers are now well versed in the application of both regulations and their alignment with the new legislative framework and the market surveillance regulations1-3. Concepts such as economic operators, market surveillance, customs controls, and enforcement are significantly reinforced in the sectorial legislation and far better understood by industry. In addition to the primary legislation, MDR and IVDR also introduced of a number of pieces of secondary legislation (implementing acts and delegated acts) that manufacturers should be aware of. Examples include the following: Regulation (EU) 2021/2226 on electronic instructions for use of medical devices Regulation (EU) 2022/2347 regards reclassification of groups of certain active products without an intended medical purpose Regulation (EU) 2023/2197 regards the assignment of Unique Device Identifiers for contact lenses These implementing acts and delegated acts provide procedural and technical details to support the implementation of the MDR and IVDR. They should be used in conformity assessments whenever they are relevant. Nationtal Legislation   While the MDR and IVDR are EU regulations and are directly applicable in all EU Member States, certain aspects require or allow for national implementation or additional national rules. National legislation can include provisions for the following: Clinical investigations Market Surveillance and Enforcement/fines Registration of Economic Operators Language and Labelling Requirements Manufacturers must familiarise themselves with applicable national legislation and incorporate this into their market access strategies. Relevant Horizontal Legislation Manufacturers can however be misled into a false sense of security because of the underlying complexity associated with the application of EU legislation. CE marking a medical device or IVD often requires a hybrid approach which considers both the sector-specific harmonisation legislation and other horizontal legislation.  Analogy can be drawn with standards where both sectorial (product standards) and horizontal standards (e.g. ISO 14971) may apply. Generally speaking, the CE mark is required for products that address health, safety, environmental, and consumer protection requirements. In the EU there are currently thirty individual types of harmonisation legislation (sectorial) that are aligned with the new legislative framework approach. CE marking is mandatory for products covered by harmonisation legislation that explicitly require it. Some notable examples that have the potential to apply to medical devices include: RoHS - Directive 2011/65/EU Electromagnetic Compatibility - Directive 2014/30/EU Radio equipment - Directive 2014/53/EU Low Voltage - Directive 2014/35/EU Batteries - Regulation (EU) 2023/1542 Machinery - Regulation (EU) 2023/1230 Artificial Intelligence Act - Regulation (EU) 2024/1689 Packaging and Packaging Waste - Regulation (EU) 2025/40 The are other EU regulations that are not harmonisation legislation per se but interact with harmonisation legislation. In other words, they do not require a CE mark in and of themselves in isolation. These are best understood as horizontal legislation that underpins and complements sectorial legislation. Horizontal rules refer to cross-sectorial regulations or guidelines that apply across multiple industries or policy areas, rather than being limited to a specific product or sector. These rules are designed to ensure consistency, coherence, and fairness in the application of EU law. Some notable examples that have the potential to apply to medical devices include: REACH Regulation – Regulation (EC) No 1907/2006 CLP Regulation (EC) No 1272/2008 Product Liability Directive – Directive 85/374/EEC / Directive (EU) 2024/2853 General Data Protection Regulation (GDPR) – Regulation (EU) 2016/679 In most cases, it is almost impossible for a medical device to be CE marked solely based on compliance with the medical device or IVD sectorial legislation alone. There are multiple other sectorial regulations and horizontal regulations that may apply in addition to the MDR or the IVDR. All applicable EU legislation should be applied to a device when it is CE marked and captured in a single declaration of conformity. Therefore, CE marking is more than just an exercise in complying with the MDR or IVDR. Medical device software is one possible exception because it can be delivered and consumed electronically and is essentially a digital asset. Therefore, there is a lower potential for other regulations to apply compared to physical devices. However, even software is subject to the product liability directive as far as defective products and financial coverage are concerned. Other EU rules related to artificial intelligence and cybersecurity may also apply to software. Implications for QMS Design Manufacturers need to take proactive steps to ensure that their quality management systems are designed to comply with all applicable regulations relating to products. In the past manufacturers have typically designed their QMSs specifically to comply with the requirements of ISO 13485, MDSAP and the medical device regulations in the EU and USA. However, increasingly it is necessary to design the QMS more broadly so that it considers aspects for all applicable regulations. For example, does the QMS require the consideration of other regulations as sources of design input or labelling. Example: Active Implantable Device Let us look at this through an example: A manufacturer of a fictitious active implantable device. The device contains a battery, electrical circuits/components, software/firmware and can use radio frequency communications to communicate with a controller or programmer. In this example the medical device sectorial legislation is the primary legislation governing the CE marking of the device. And in this case a Notified Body designated under the MDR will complete the conformity assessment. However, the device will also fall under the requirements of the RoHS directive (for the materials used in the electrical circuits/components), the radio equipment directive (for the communications), the NIS 2 Directive (for cybersecurity), the batteries regulation (for the battery) and the packaging regulation (for the packaging). In addition, the materials will need to be assessed in line with the REACH and CLP regulations. If the device collects, stores, transmits, or otherwise processes personal data GDPR applies. In this case the device can only be CE marked when the applicable requirements of all the aforementioned directives and regulations have been fulfilled, and a single declaration of conformity drawn up. This may necessitate additional technical documentation and objective evidence for compliance. While the Notified Body is primarily focused on the review of the objective evidence related to compliance with the MDR, they can equally ask about the evidence to support other regulations. New and Changing Regulations There remains an ever-increasing production line of new and changing regulations in the EU that have the potential to affect medical devices. Often these are outside the core competencies of traditional medical device companies and their R&D, QA, and RA departments. Companies who can adapt, upskill, and move with the times will undoubtedly have the competitive advantage in the future when it comes to compliance and market access. The key enabler is building a management system that is constructed based on all applicable regulations and not just the narrow sectorial legislation for medical devices which has historically been the case. Also, manufacturers who can develop a holistic view of EU regulations and make it part of their regulatory intelligence process will be set up for future success. See our related blog on this topic. Summary The process to CE mark a medical device  or IVD requires a comprehensive evaluation of all applicable harmonisation legislation, horizontal regulations and member state national legislation. CE marking based on the medical device regulation or IVD regulation alone is seldom sufficient to achieve a fully compliant and marketable device. Manufacturers must develop comprehensive and complete market access strategies to address all applicable requirements. In the context of the broader EU legal framework, the MDR and IVDR present several complexities and pain points that go beyond the regulations themselves. These challenges stem from how MDR and IVDR interact with other EU laws, institutions, and market dynamics. This multi-layered compliance increases complexity, especially for SMEs that lack regulatory resources. Related next steps If you’re having difficulty navigating the EU regulatory landscape and struggling to comply with horizontal EU regulations, our experts specialise in helping manufacturers develop comprehensive regulatory strategies designed to ensure that medical devices and IVDs comply with all applicable EU legislation. Contact us to discuss how we can support your efforts and stay tuned for more updates related to the European Medical Device landscape in our upcoming blog posts. Regulation (EC) 765/2008 setting out the requirements for accreditation and the market surveillance of products Decision 768/2008 on a common framework for the marketing of products, which includes reference provisions to incorporate in product legislation revisions. In effect, it is a template for future product harmonisation legislation Regulation (EU) 2019/1020 on market surveillance and compliance of products Further reading - Opportunity & Risk: Why we should open our minds to off-label use #### MitraClip and the Business of American Healthcare: Innovation, Inefficiency, and the Cost of Care Clipped Hopes and Golden Profits: Innovation or Ingenious Marketing? The MitraClip, a tiny device that patches leaky heart valves without the need to crack open a chest, has been hailed as a medical marvel. But is it a game-changer or a high-priced Band-Aid? With clinical truths fresh from RESHAPE-HF2 and an unflinching look at the forces shaping medical innovation, here we dissect the real winners, the hidden losers, and whether the MitraClip is a lifesaver or a profit-making illusion. The human heart beats for survival, but the healthcare industry? It beats for returns on investment. Why Everyone’s Fighting Over This Tiny Clip Okay, let’s settle this feud first: Why can’t we all just get along? Same Device, Different Patients: The COAPT, MITRA-FR, and RESHAPE-HF2 Conundrum Lately, the MitraClip has been tested in three major trials namely, COAPT, MITRA-FR, and RESHAPE-HF2. However, each of their conclusions (apart from being hypothesis generating…which is a missed opportunity) seem like they’re describing three different devices. Why? Because the patients weren’t the same, and in medicine, that changes everything. COAPT (2018) [1]: The Headliner Patients had severe mitral regurgitation (MR) but hearts that weren’t too far gone. Think of a car with a fuel leak but an otherwise decent engine. The Clip worked like magic here; it chopped hospital trips by 47% and kept folks alive. It looked like a blockbuster. Confetti cannons! MITRA-FR (2018) [2]: The Buzzkill Same clip but these patients had severe MR, and their hearts were already stretched like an overinflated balloon. The Clip did nothing. It fizzled harder than my attempt at keto. Why? Because fixing the leak couldn’t save an engine already breaking down. RESHAPE-HF2 (2023) [3]: The Solid Meh The “let’s meet halfway” trial. Moderate leaks + advanced heart failure. The Clip cut hospital visits but didn’t necessarily keep patients alive longer. A solid “Cool, but where’s the meat?” outcome. The Perils of Apples-to-Oranges-to-Grapefruit Comparisons These trials didn’t contradict each other; they studied different patient populations. COAPT picked the “ideal” patients, MITRA-FR studied sicker real-world cases (with more dilated left ventricles), and RESHAPE-HF2 landed somewhere in the middle, reminding us that medicine (and medical device) aren’t a one-size-fits-all hat. But here’s the problem: clinicians and insurers often generalize COAPT’s success with all heart failure patients, leading to overuse (40% off-label) and disappointment. Why This Matters? Heterogeneity = Confusion: Each trial tested different “flavors” of heart failure, but their results get lumped together. The Clip Isn’t a Magic Bullet: It works for certain leaks in specific hearts but not all. So, before we crown the Clip a miracle or call it a medical mirage, let’s follow the money and see what happens outside the clinical trials. Payers: “Save 8K Now, Cry Over 50K Later” Let’s talk cash, because someone’s got to foot the bill. The MitraClip costs around $30K per device, and some patients get more than one Clip in a single procedure [1]. Payers grit their teeth but save $8K upfront by dodging ICU stays and repeat hospitalizations, so far, so good [2]. Cha-ching! But here’s the plot twist: 24% of (functional leaks) patients need a repeat fix within five years [3]. Whether it’s another Clip, surgery, or a bailout strategy, the costs keep climbing. Total bill? $50K+ per patient over five years [4]. That’s like buying a Tesla that keeps stalling at stoplights and the dealership tells you to just buy another one. Payers are trapped in a “save now, pay later” loop, the financial equivalent of Groundhog Day meets The Wolf of Wall Street. Except instead of Leonardo DiCaprio, it’s insurers pacing their boardrooms wondering how they got here. Doctors & Researchers: “Hold My Scalpel, I’m Clipping Anyway!” Here’s the scoop: 40% of U.S. Clip use is not per the “rules” [5]. MITRA-FR screamed “It doesn’t work for stretched-out hearts!” [2] and RESHAPE-2 proved surgery’s better for those cases [1]. So why do hospitals keep clipping? Well, it’s quick, profitable, and physicians get paid either way. It’s the medical version of DoorDash; convenient, but you might end up with cold fries. The Fix: Lock the Clip in a vault for “broken valve” patients only (where it works best: 10% failure rate) [1]. Everyone else? Maybe try not using a dessert spoon for open-heart surgery. Big MedTech: “Why Fix It When It’s a Cash Cow?” MitraClip owns 85% of the $2B mitral valve market [4]. Competitors like Pascal, Cardioband, etc.? They’re playing solitaire in the waiting room. Newer Clips (looking at you, G4) promise easier use…but there’s zero proof they’re better long-term. It’s like iPhone updates: “Ooh, new emojis and a cooler camera!” but your battery still dies at 3 PM. Perhaps real innovation has stalled because why fix what’s printing money? The Big Fight: “Innovation vs. the 24% Time Bomb” The Clip’s Dirty Secret: It’s gold for “broken valves” (mostly in rich countries) but has a 24% failure rate in “functional leaks” (which is the more widely occurring condition) [1]. Trial Wars: COAPT (pro-Clip) vs. MITRA-FR (anti-Clip): Same device, opposite results. Why? COAPT picked healthier hearts; MITRA-FR included sicker (more real-world) patients [1,2]. RESHAPE-2’s Verdict: Surgery beats the Clip in functional leaks. Take that, optimism! The Fix: Regulators should force companies to prove devices work AND reach those who need them most. No more “innovate first, ask questions never.” Regulators: “Approve First, Pray Later” The FDA greenlit Clip use for “functional leaks” in 2021 [6], even though 1.2% of Clips come off and yeet themselves into the bloodstream [6]. Europe came through with a, “Hold my espresso,” and demanded long-term data [3]. All the while, patients get risky care faster. Safety, effectiveness, cost-effectiveness? That’s Future Us’s problem. The Future: “Beyond the Clip or Bust” New contenders? Game-changing implants that remodel hearts, AI wizards like EchoGo Core. The snag? They’re trapped in R&D purgatory while the Clip soaks up all the limelight…and every eligible patient. The dream? A power duo: Clip + heart-fortifying tech. The reality? Trials crawl at a glacial pace, thanks to sluggish enrolment because, surprise, surprise, everyone’s already clipped! It’s like trying to start a band when the only drummer in town just signed an exclusive deal. The Unseen Forces Fueling the Crisis A. The Training Trap: Industry-Taught Tunnel Vision Manufacturers subsidize physician training programs, teaching how to use the Clip but not when to avoid it [7].  All cooking comes down to, let’s Deep-fry ALL THE THINGS! This turns physicians into “Clip-first” operators, even when meds or surgery might work better. B. The Vanishing Surgeon: Skills Lost to the Clip Surgical mitral valve repairs in the U.S. dropped 35% (2015–2023) as Clip use soared [8]. Fewer surgeons train in open-heart repair. Long-term risk? No backup plan for Clip failures. C. Innovation Lock-In: Protecting Profits Over Patients Hospitals invest millions in Clip-friendly cath labs. Once locked in, they block out competitors to protect investments [9]. The result? Prioritizing Clip volume over outcomes. D. The Demographic Mismatch: Solving the Wrong Problem Low- and middle-income countries (LMICs) are stuck in a paradox: bursting with young patients who need solutions for rheumatic fever-ravaged valves (courtesy of untreated strep and scarlet fever), yet the Clip is tailor-made for age-related leaks. It’s like showing up to a famine with a wine tasting; elegant, sophisticated, and utterly useless for those who need it most. The Path Forward Precision Over Panic: Use AI-guided echocardiography to identify COAPT-eligible patients: severe MR + salvageable myocardium. Avoid Clipping in MITRA-FR-like patients (severe LV dilation, advanced remodeling). Better Trial Design: Stratify by LV size (phenotype trials), fibrosis biomarkers, and track quality-of-life metrics alongside survival for a more nuanced picture. Global Guidelines: Ditch one-size-fits-all MR thresholds with graded recommendations. Say: “Clip only if LVEDD <65mm” (translation: only if the heart isn’t too stretched out) [1]. The Final Cut: Who’s Really Winning? The MitraClip isn’t just a device, it’s a mirror reflecting healthcare’s broken priorities. If we want to fix this mess: Clip the Hype: Save the Clip for the right patients and stop the 40% off-label use [3]. Demand Real Proof: No more approvals without proving the device works AND doesn’t bankrupt the system. Bridge the Chasm: Cut costs for poor countries where a majority of cases could actually benefit [6]. The Heart of the Matter The Clip’s rollercoaster results scream: Context is king. Ask not “Does it work?” but “For whom?” The future? Going with precision, not panaceas. More from this author: White paper: Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation Technical brief: Bridging Treatment Gaps in Heart Failure with Reduced Ejection Fraction: Advancing Evidence for Device-Based Therapies Technical brief: Beyond Inclusion: Reimagining Equity and Real-World Impact in Heart Failure Trials On-demand panel discussion: Medical Device Cybersecurity: Proven Strategies for Connected Devices and SaMD Global Perspectives: Comparing Regulations for Point of Care Tests in the U.S. and EU References 1.    Stone GW, et al. RESHAPE-2 Trial. N Engl J Med. 2023;388(12):1123-1135.2.    Obadia JF, et al. MITRA-FR Trial. N Engl J Med. 2018;379(24):2307-2318.3.    Chhatriwalla AK, et al. Off-label MitraClip Use. JAMA Cardiol. 2022;7(3):247-255.4.    Abbott Laboratories. MitraClip Market Report. 2023.5.    FDA MAUDE Database. Device Embolization Reports. 2021.6.    Zühlke LJ, et al. Rheumatic Heart Disease in LMICs. Lancet Glob Health. 2020;8(6):e711-e723.7.    Ettinger KM, et al. Industry Influence on Physician Training. Circ Cardiovasc Qual Outcomes. 2021;14(8):e007854.8.    STS Adult Cardiac Surgery Database. Mitral Valve Repair Trends. 2023.9.    Smith CR, et al. Hospital Device Adoption Bias. Health Aff. 2022;41(4):567-575.10.    Watkins DA, et al. Global Burden of Rheumatic Heart Disease. N Engl J Med. 2017;377(8):713-722. #### Molecular Weight Analysis: How to Measure MW? Analyzing the molecular weight of both natural and synthetic polymers is extremely complex, and almost impossible to carry out with exactness. Unlike elemental analysis – which focuses on the chemical composition of samples under test – molecular weight analysis considers the number of small molecules present in a polymeric chain. This number can vary significantly, even within specific polymer groups. Yet accurate molecular weight analysis is an important part of quality assurance and control (QA/QC), providing the means for process engineers to assess various product performance parameters. The molecular weight – or MW – of plastics is a good indicator of important mechanical properties such as durability, strength, and toughness. In bioactive polymers, such as those found in drug delivery systems, MW can determine the release rate of pharmaceutical compounds in vitro. So, it is often vital to perform robust molecular weight analysis to get the greatest results from polymeric goods and systems. At RQM+ Lab Services, we are experts in molecular weight determination, with an excellent grasp of the underlying theory of MW measurements and the necessary tools to complete any analytical run. This is how we perform molecular weight analysis. Molecular Weight Analysis: The Basics First, we should revisit the idea that molecular weight is not a definitive number but is instead based on a series of values that form a bell curve distribution that indicates an average MW value. Calculating this distribution is carried out by multiplying the mass of each repeating monomer in the polymeric chain then adding the mass of either end group. In the resulting bell curve, the lowest portion of the curve is the number average MW (Mn) while the highest portion is known as the Z average (Mz). That which is closest to the middle of the curve is the weight average (Mw). Molecular Weight Analysis, the RQM+ Way At RQM+ Lab Services, we rely on our demonstrable expertise in gel permeation chromatography (GPC) to measure the molecular weights of various polymers with absolute precision. This is the industry-standard technique used to separate compounds into their composite parts by various molecular properties, including weight. Using a host of accurate detection technologies (multi-angle light scattering, refractive index, viscometry, etc.) we can determine the entire MW distribution of samples separated via a choice of GPC columns. Our background in GPC column design and engineering makes RQM+ Lab Services the go-to provider of GPC-related services and studies. Or, for any questions regarding molecular weight analysis for specific polymer grades and types, simply contact a member of the RQM+ Lab Services team today. #### Musical Chairs MDR-Style: Keep Dancing Even Though the Music Has Stopped Introduction We have previously talked about the upcoming 2024 EU deadlines for QMS compliance and notified body applications for the EU MDR 2017/745 (5 Essential Tips for EU MDR Compliance and How to Meet the EU's 2024 MDR Deadlines), but what is needed beyond that? What if you have your contract in place with a notified body and your technical documentation is ready for assessment now? There are varying lead times at each of the notified bodies; these times depend on the notified body and the applicable codes for your product. Realistically, the actual conformity assessment may not start for another 18 months, but your technical documentation has sat in a queue for some time waiting for the review to start. What should you do in the interim?  When you submitted your technical documentation, all the documents were shiny and new, but by the time the conformity assessment has started – a year or two may have passed – and suddenly your notified body is asking for updated risk documents, the latest post-market surveillance (PMS) reports, updated clinical evaluation reports (CER), reviews of updates to the latest standards, and so on. What should you do?  Here are 5 tips on how to be effective while waiting. 1. Don't stand still Act like you already have your CE certificate.   Run your processes to generate the evidence to demonstrate that your process outputs support your MDR compliance efforts (e.g. evidence that shows how your PRRC is actively fulfilling their duties as described in Article 15 of MDR 2017/745 and MDCG 2019-7, such as ensuring that the technical documentation is kept up-to-date and that post-market surveillance activities are implemented effectively).   Execute your PMS and post-market clinical follow-up (PMCF) plans, including keeping your finger on the pulse of the changes in the generally acknowledged state of the art. This includes ensuring that new MDCG guidance is not overlooked; assessing changes to regulatory and/or product requirements; ensuring that new and updated standards are considered and reviewed for applicability, and where applicable their impact on your product, processes or data is understood. Produce your Periodic Safety Update Reports (PSURs) as defined in your PMS plans, at the required frequency for the device classification.  Ensure that your feedback loops for post-market data are working; remember, the post-market surveillance requirements have been applicable since May 2021., Use the outputs from your PMS process to update your Clinical Evaluation Reports (CERs) and risk management files as necessary to ensure that your benefit-risk determination is being reviewed and updated.   Update your technical documentation and all supporting documents as is needed to demonstrate conformity with the requirements of the MDR.  If you are making non-significant changes to your legacy device and your legacy device is transitioning to MDR CE certification, you will need to reflect those changes in your Technical Documentation to ensure that the MDR certification review is conducted on contemporaneous evidence.  2. Evidence of validity As discussed in our 5 Essential Tips for EU MDR Compliance, don’t forget to utilize the self-declarations and notified body declarations to confirm that your certificates and legacy devices meet the conditions laid out in Regulation (EU) 2023/607 so that you can demonstrate to your customers that your legacy devices can still be placed on the market legally. These declarations may need to be maintained as key information and statements contained within changes. 3. Keep your eyes and ears open As more and more devices go through certification, more feedback is available. This includes insights on the types of questions being asked, the depth of analysis or justification that is being deemed acceptable by the Notified Body reviewers and the expected (and accepted) content for documents such as the Summary of Safety and Performance (SSCP). Keep tabs on webinars, bulletins and whitepapers from the Notified Bodies, and updated guidance or papers from Team-NB. These will all help you gauge the current expectation levels and be ready to answer questions/requests once the review starts.  4. Have data, will upload Further delays to the dates for mandatory use of EUDAMED have just been announced, with 2027 now looking like the new date for mandatory use of most modules. Ignore EUDAMED uploads at your peril; do not wait until the announcement of EUDAMED readiness is published in the Official Journal of the EU before acting. Those watching all things EUDAMED have highlighted situations, including Olga van Grol-Lawlor in our recent Live! show, where competent authorities and economic operators are pushing hard for all data to be uploaded into EUDAMED now. If you have the data ready, it may be prudent to ignore the delayed implementation dates and upload the data to EUDAMED now. Take this time to rigorously check its accuracy to avoid problems further down the road 5. Be transparent Be clear with your notified body that you are maintaining your technical documentation. Confirm with your notified body whether they want you to submit updated documentation as it is available, or only once the review starts in earnest. Clarify with your notified body what they will be looking for in terms of PSUR timeframes, as your reporting frequency may fall out of sync with when the notified body wants an updated PSUR. In the absence of any agreement, once you get confirmation that the review is to begin, ensure that your reviewer knows that documentation has been updated and make it available for inclusion in their review. Do not be shy about it. You do not want to waste any of your permitted review questions on basic requests for the latest versions of documents.  Ensure that internal communications are also as transparent; keeping relevant internal stakeholders appraised of the situation, likely timelines and any expected changes to plans etc.  Want to Know more? For next steps and more information, here are some fantastic options from our team and special guests:  Read our two recent guides: Mastering the Transition: 5 Essential Tips for EU MDR Compliance  Don’t Get Caught Off Guard: How to Meet the EU’s 2024 MDR Deadlines  Watch BSI's Richard Holborow and RQM+'s Amie Smirthwaite talk EU compliance in RQM+ Live! #69  Watch Boston Scientific’s Olga van Grol-Lawlor and RQM+’s panel review the news and insights coming from autumn 2023’s long run of MedTech conferences in RQM+ Live! #73  Follow #MedTechVoices on LinkedIn and get insights from our team as they analyze each of the opinions published by the Expert Panels as part of the Clinical Evaluation Consultation Process.  Follow RQM+ on LinkedIn for all of our updates! #### Nancy Morrison's Keys to Thriving in Regulatory Affairs: Lessons Learned from a 30+ Year Career In this heartfelt and insightful video presentation, Nancy Morrison – as highly a respected professional as you'll ever find in regulatory affairs – shares her journey and the lessons she's learned along the way. As she embarks on her well-deserved retirement, Nancy generously takes the time to impart her wisdom and provide guidance to those aspiring to build a successful career in regulatory affairs. Throughout her career, Nancy has made significant contributions across many roles, from quality assurance to regulatory affairs, and finally as a consultant. Her unique perspective, shaped by personal experiences and an encyclopedic understanding of the industry, offers actionable insights into what it takes to excel in this field. In her presentation, which features a brief introduction from RQM+ VP of Global Regulatory Affairs, Jaishankar Kutty, Nancy discusses the importance of embracing challenges, building credibility, and fostering positive relationships with colleagues and regulatory bodies. She emphasizes the significance of understanding the "why" behind regulations and encourages viewers to seek out new opportunities and innovative approaches. Drawing from her own life, Nancy shares the story of her son Matthew, who relies on numerous medical devices daily. This personal connection underscores the crucial role regulatory affairs professionals play in ensuring the safety and effectiveness of products that directly impact patients' lives. As you watch this video, you'll gain a deeper appreciation for the dedication and expertise required to succeed in regulatory affairs. We believe Nancy's insights and personal story will definitely inspire and guide you on your own career path, helping you successfully navigate the complexities of the regulated industry with confidence and purpose. And from RQM+, Nancy... we couldn't possibly put into words how much we appreciate you and the positive contributions you've made to our clients over the years. You've changed the MedTech industry for the better in immeasurable ways. Thank you. On Tuesday, 16 April (next week) and prior to her retirement, Nancy will be presenting a live webinar: Aligning Your QMS with the FDA's QMSR Updates. Register here. #### Navigating PFAS Regulations: Lab Analysis for Medical Device Material Changes Regulations in both the EU and US are rapidly changing in order to address the health and environmental risks posed by per- and poly-fluoroalkyl substances (PFAS). Through the EU REACH regulation, it has been proposed to restrict PFAS which will preclude manufacturers from placing PFAS-containing devices on the EU market 2030 onwards. Similarly, in the US the states of Maine and Minnesota have enacted restrictions and registration requirements on products known to contain PFAS. These regulations, as well as those likely to come in the future, will cause medical device manufacturers to assess and possibly remove PFAS containing materials from their devices. In turn, new materials will be added to the devices as replacements. The expectation from regulators when this type of change occurs is to reassess the biocompatibility and toxicological risk posed of new leachable chemicals for the device with these new materials. We will discuss here the steps that can be taken to efficiently perform this type of assessment for on-the-market devices undergoing material change. What are per- and poly-fluoroalkyl substances (PFAS)? In order to determine if a device might need to be considered for a material change, it’s important to understand what PFAS are and how they are used in medical devices. PFAS represent a large series of related chemicals (with more than 15,000 known) with alkyl functionality, but where some (polyfluoroalkyl) or all (perfloroalkyl) hydrogen atoms are replaced with fluorine. The most common of these materials is polytetrafluoroethylene (PTFE), often referred to by the trade name Teflon. This material has a number of advantageous properties, including high thermal and chemical resistance as well as high lubricity. Other materials common for medical devices that may contain PFAS include processing and manufacturing aids, lubricants, and coatings. A thorough examination of the bill of materials for a device may be sufficient to determine the presence or absence of these materials. However, there are laboratory methods that can be used to screen for PFAS to confirm. Navigating Material Changes in Medical Devices If a material change is found to be the best course of action to avoid potential regulatory problems associated with PFAS, regulators will expect a reassessment per the ISO 10993 series of recommendations. The general guidance section of ISO 10993-1:2018 states: “It is important to understand that although material changes do trigger the need for re-evaluation, the scope of that re-evaluation should be appropriate to the nature of the change and should focus on the specific materials changed, the nature and use of the medical device and the potential interactions.”   One of the more complex aspects of such re-evaluation is the chemical characterization performed with recommendations in ISO 10993-18.  In this context the standard states “The purpose of such a comparison would be to establish whether the new or modified medical device is biologically equivalent to the existing medical device since if biological equivalence can be established then the existing medical device’s biocompatibility can be extended to the new or modified medical device.” This type of comparison, between a current (predicate) device and a device with modified materials (proposed), can be challenging. This is especially true for more complex devices (resorbable, those containing biological materials) or permanently contacting devices. In these cases, it is common for there to be a larger overall number of extractables that may need risk assessment. For all studies attempting to support the equivalence of predicate and proposed devices, it is critical that a robust process is in place allowing efficient comparison of observed extractables. Jordi Labs employs a process by which statistical evaluation of mass spectral data is used to accurately and quickly differentiate those compounds that are common (within the expected error of the analytical methods applied) and those that are new or changed for the new, PFAS-free, device. Focusing downstream toxicological risk assessment on these compounds allows a study sponsor to save precious time in getting the new PFAS-free device on the market ensuring patients are not exposed to PFAS or new potentially toxic chemicals from replacement materials. RQM+ and Jordi Labs team of experts are eager to guide you through the complexities of PFAS regulations and their impact on your products. If you have already made material changes to your device, we can immediately help by providing testing to support equivalence with current devices. To find out more about how we can help with extractables and leachables, contact us today. For more information on emerging concerns with PFAS materials you can download our white paper: Are We Equipped to Handle a PFAS-Free Future? #### New FDA Dataset Marks a Transformative Leap for Chemical Characterization We're thrilled to announce a significant development from the FDA’s Center for Devices and Radiological Health (CDRH) that introduces a new regulatory science tool for chemical characterization. This groundbreaking tool is a huge step moving toward improved chemical characterization methods that fits well with Jordi Labs current procedures.   A Step Towards Enhanced Safety and Efficacy in Medical Devices The FDA's latest initiative marks a crucial milestone for the chemical characterization field. The launch of the Chemicals List for Analytical Performance (CLAP) tool by the CDRH is a significant step towards enhancing the safety and efficacy of medical devices. This tool will provide labs with a benchmark for assessing analytical method adequacy through an initial set of chemicals and their associated relative response factors (RRF), which have been selected based on a broad spectrum of physicochemical properties. Jordi Labs by RQM+ at the Forefront It’s a proud moment for us at Jordi Labs, as our longstanding commitment and advocacy for rigorous chemical characterization approaches have helped to lay the groundwork for this initiative. Our team’s proactive approach in establishing a broadly constituted relative response factor database and deriving appropriate uncertainty factors has been industry-leading, and the publication of FDA’s CLAP tool represents a paradigm shift towards alignment with this approach. Industry Implications Specific guidance regarding analytical method adequacy for device chemical characterization studies is currently lacking in the ISO 10993-18:2020 standard. Furthermore, the accepted practices for characterizing the uncertainty of analytical methods and deriving uncertainty factors for analytical evaluation threshold (AET) application are based either on arbitrary values or on statistical calculations which are unsuitable for the methods commonly used for this testing. The FDA's endorsement of approaches that align with our practices signifies a pivotal change in the industry. It encourages other labs and organizations to adopt more robust testing approaches, ensuring better patient outcomes. As the FDA continues to expand this database to include additional gas chromatography data and additional methods, such as liquid chromatography, Jordi Labs remains committed to transparency with the FDA regarding our approaches. Our Continuous Advocacy for Excellence Several years ago, Jordi Labs recognized the need for more comprehensive standards in dealing with uncertainty in analytical instrument responses. Unlike many others content with the status quo, our lab embarked on a rigorous effort to challenge and change the existing norms. Our work in this area has not only been about advancing our capabilities but also about setting new benchmarks for the industry. The publication of our findings and the implementation of these standards in our lab back in 2020 were just the beginning. Together, let’s continue to set new standards and ensure that our advancements in chemical characterization not only meet but exceed regulatory expectations, paving the way for safer medical devices around the globe. Contact our team today to learn more about how Jordi Labs by RQM+ can support your full lifecycle materials science and chemical characterization needs. #### New Guidance: FDA Safer Technologies Program (STeP) for Medical Devices U.S. Food & Drug Administration (FDA) released the highly anticipated Safer Technologies Program (STeP) Guidance Document. By: Nancy Morrison, RQM+ Executive Director, Regulatory and Quality Consulting Services and Kevin Go, RQM+ Project EngineerKicking off the year on a high note, the U.S. Food & Drug Administration (FDA) released the highly anticipated Safer Technologies Program (STeP) Guidance Document earlier this month. The final guidance document comes just a little over a year after the draft was first released, which is especially impressive timing given the Center for Devices and Radiological Health's (CDRH) workload with all the COVID-related submissions. Per the Guidance Document, the STeP is a: “new, voluntary program for certain medical devices and device-led combination products that are reasonably expected to significantly improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and mortalities less serious than those eligible for the Breakthrough Devices Program; for example, this may include devices treating or diagnosing non-life-threatening or reasonably reversible conditions.” FDA’s SteP is based off the Breakthrough Devices Program and share many similarities between their processes, timelines, mechanism of feedback, and level of interaction with FDA. Like the Breakthrough Devices Program, PMA, De Novo, and 510(k) products are all eligible for STeP. The major difference between the programs is in the eligibility criteria. The criteria for a medical device or combination device to participate in the STeP is: Device is for less serious diseases or conditions and, consequently, is not eligible for the Breakthrough Devices Program Device meets one of the following: Reduction in known serious adverse events Reductions in known device failure mode Reduction in known use related hazard or use error Improvement in safety of another device or intervention There are a few important points to note regarding eligibility for the STeP designation. First, the eligibility for the second criteria should not be based on hypothetical adverse events/failure modes. To be able to demonstrate a significant safety improvement, the device must show a reduction in an “known” safety event. It is also important to note that inclusion in STeP does not change the statutory and regulatory requirements of your devices. While being able to demonstrate reduction in a “known” safety risk would improve the benefit-risk determination, it would not change the devices overall risk classification (i.e. a PMA would still be a PMA). The SE evaluation for 510(k)s will also not be impacted by inclusion of the device in STeP, meaning that “substantial safety innovations” may still raise different questions of safety and effectiveness and be kicked off the flowchart. To submit a request for your medical device or device-led combination product for the SteP designation you must do so in a Q-Submission, with the request being the only item in the Q-Submission. FDA expects to request any additional information within 30 days of the request and a final decision made within 60 days. An example of the type of information which should be included can be found in Appendix 1 of the Guidance Document. To expedite timely reviews, device manufacturers can expect faster feedback from FDA via “Sprints”, meaning single topic pre-submission meetings and 45-day timeline per topic. Additional benefits of the program include: Flexibility in clinical study design Expedited pre-approval inspection for PMA submissions Opportunity for more interaction with FDA via regular status updates outside formal submissions Just like the FDA Breakthrough Devices Program, there is a commitment on the part of the sponsor to respond quickly to interactive review questions to take full advantage of this expedited program. This increased communication is especially beneficial for those complex submissions where clinical data is needed or where multiple interactions with the Agency are common. FDA also notes that multiple regulatory submissions for devices intending to address the same safety issue may be pending simultaneously. Interestingly though, the guidance does not provide examples for what happens if one device addressing the same safety issue gets cleared before another. They provide similar examples in the Breakthrough Guidance, so it is possible that something similar will happen where the benefit-risk for the devices still under review will have to be adjusted after the first one is cleared, or they may end up being disqualified. >> Read now: FDA’s Tool for Assessing Medical Device Cybersecurity Vulnerabilities The RQM+ team is very excited about this new program! STeP fills in the gaps for devices that target important conditions that are not covered by the Breakthrough Devices Program and provides another mechanism to get safer treatments more quickly to the patients who need them. While the Guidance Document has been finalized, however, it is important to note that FDA is not accepting any requests at this time. FDA anticipates that the “Agency may need up to 60 days to perform activities to operationalize this Safer Technologies Program following issuance of this guidance”, meaning they still need additional time to be able to train the CDRH review and policy staff on how to interpret and implement the new program appropriately. FDA is hosting a webinar on February 1, 2021, where we will hopefully learn more information about their progress and when the program will go live. Announcing RQM+R&Q and Maetrics have merged to form the world's leading medical device and diagnostics consultancy, and we're ready to help with your FDA Regulatory needs! Check out our Regulatory services for more information and learn more about RQM+ More resources at your fingertips.Subscribe to our Resources blog for all upcoming and on-demand education available from RQM+, including industry-leading webinars, biweekly RQM+ Live! shows, commentary from our thought leaders, Q&A features, and more. Sources:[1] U .S. Food & Drug Administration (FDA). Safer Technologies Program for Medical Devices: Guidance for Industry and Food and Drug Administration Staff. Published 6 January 2021. Accessed 6 January 2021. https://www.fda.gov/media/130815/download[2] U.S. Food & Drug Administration (FDA). Safer Technologies Program (SteP) for Medical Devices. Published 6 January 2021. Accessed 6 January 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologies-program-medical-devices[3] U.S. Food & Drug Administration (FDA). Breakthrough Devices Program. Published December 2018. Accessed 6 January 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-devices-program #### One Year Countdown: Preparing for the FDA's QMSR Implementation As we mark the one-year anniversary of the FDA's final rule on the Quality Management System Regulation (QMSR), we wanted to post a friendly reminder that we now have only one year left until the rule is fully in effect. The QMSR, which aligns with ISO 13485:2016, will be enforced starting February 2, 2026. This transition represents a shift in QMS requirements for medical device manufacturers in the U.S., and it's essential for manufacturers who don't have an ISO 13485:2016 certified QMS to start working on implementation if you haven't already. Why the QMSR Matters The QMSR aims to harmonize and modernize the current good manufacturing practice (CGMP) requirements for medical devices (and combination products), promoting consistency and ensuring the timely introduction of safe, effective, and high-quality devices. By aligning with ISO 13485:2016, the QMSR brings U.S. regulations in line with international standards, facilitating global market access and improving overall quality management practices. Key Steps for Implementation If your organization hasn't started the transition process yet, now is the time to act. Here are some critical steps to ensure compliance by February 2026: 1. Assess Your Current QMS Evaluate your existing Quality Management System to identify gaps and areas that need updating to meet the new QMSR requirements. 2. Update Documentation Ensure all documentation, including procedures, work instructions, and records, align with the QMSR and ISO 13485:2016 standards. 3. Training and Education Provide comprehensive training for your team on the new requirements and their implications for daily operations. 4. Risk Management Incorporate risk management principles throughout your product lifecycle, as emphasized by the QMSR. 5. Internal Audits Conduct internal audits to verify compliance and identify any areas needing improvement before the FDA's enforcement date. Additional Information: The FDA is working to update its guidance documents to be consistent with the QMSR. The FDA intends to develop a new inspection process to align with the requirements of the QMSR. The FDA considers the QMSR to be substantially similar to the QS regulation and does not expect there to be many differences in interpretation of the regulations or application of relevant policies. Final Thoughts and Call to Action The countdown to February 2026 is on and the time to prepare is now. By taking proactive steps to align your QMS with the QMSR, you'll not only ensure compliance but also enhance the quality and safety of your medical devices. If you need assistance with the transition, our team at RQM+ is here to help. Contact us today to learn more about our services and how we can support your journey to compliance. ISO 13485 is a critical part of the regulatory framework for medical devices globally. This status is reflected in its title, “Medical devices — Quality management systems — Requirements for regulatory purposes”, where it is not only a sector-specific (i.e. the medical devices bit) quality management system (QMS) standard, but it is also directed towards the regulatory requirements related to a QMS (i.e. requirements for regulatory purposes and the numerous “applicable regulatory requirements” dotted throughout the normative text). This focus means that conformity to ISO 13485 supports market access across many different countries and regions, and provides customers and other stakeholders with some assurance that the respective organization is adhering to specific requirements and best practices related to their role in the medical device industry. The scope of ISO 13485 applies to all types of medical devices (and I include in vitro diagnostic medical devices and software as a medical device in that, too) and all organizations involved in the lifecycle of a medical device. This broad application and crucial position in the foundations of many medical device regulatory frameworks around the world make the future of ISO 13485 of strategic importance to the majority of the industry. Published in 2016, ISO 13485:2016 is the third edition of ISO 13485. It was given a 3-year review period initially and went through a systematic review in 2020 when it was confirmed (i.e. the published 2016 version remains valid and is not updated to a new edition). The review period was then set at the more traditional 5-year period, and thus ISO 13485:2016 is due for another systematic review in 2025. What is the systematic review? Standards are only worthwhile if they are kept up to date, still valid, being used (globally in the case of ISO standards), and still useful. The systematic review of ISO standards is the periodic mechanism for the national standards organizations to review published standards. In this instance, the national standards organizations will be asked whether ISO 13485:2016 is still valid, whether it needs to be updated or if it should be withdrawn. To do this, the national standards organizations should solicit feedback from their national stakeholders in order to make an informed decision in the systematic review. The Survey As preparation for the systematic review of ISO 13485:2016 in 2025, the ISO technical committee responsible for ISO 13485, ISO TC 210 WG1, opened a public survey for users of ISO 13485:2016 to provide feedback to the working group. The questions in the survey aimed to gather information on how ISO 13485:2016 is used, and perceived, by stakeholders in the medical device industry, and how the standard is valued. The survey ran during late 2023 and closed in January 2024. ISO TC 210/WG 1 published a paper, "ISO 13485-2016 Users survey - White paper on the results", outlining some of the results from that global survey. There were over 1600 responses to the survey, with approximately ⅔ of the respondents coming from organizations identifying themselves as the legal manufacturer. The survey allowed the respondents to provide feedback on ISO 13485:2016 either by selecting predefined choices, or by using free text fields. Some of the key highlights from the survey were: ~90% of respondents were very, or somewhat, satisfied with the content and use of ISO 13485:2016; Respondents indicated that their use of ISO 13485:2016 still enabled them to conform, and align, with other management system standards (e.g. ISO 9001, ISO 14001) as required; The stability of ISO 13485:2016 and its compatibility with global medical device regulations were of greater importance to the respondents than ISO 13485 following the harmonized approach for management system standards. Independent of their answers on how satisfied they were with ISO 13485:2016, survey respondents were also able to provide specific comments on each clause of the standard. Over 600 comments were submitted, which ISO TC 210/WG1 have reviewed to determine whether there is a need for technical changes to ISO 13485:2016. There were many requests for ISO 13485 to be updated to reflect the specific requirements of specific national or regional legislation (e.g. the EU MDR), but these kinds of changes would be out of the scope for an ISO management system standard. There were a lot of requests for more specific requirements for certain technologies (e.g. software as a medical device) or certain organization types (e.g. those with virtual offices), as well as calls for further guidance on how to implement the existing requirements. It was clear from the responses that awareness of the existing guidance on the implementation of ISO 13485:2016 was low (see ISO 13485:2016 - Medical devices - A practical guide), in part due to it not being a typical ISO standard format. ISO TC210/WG1 has recognised that further guidance on specific areas would be beneficial, and it should be in a format that is more visible and accessible for organizations (than the current practical guide). Therefore a New Work Item Proposal (NWIP) is underway, which if/when approved will eventually lead to updated guidance in an ISO standard format (e.g. Technical Specification or a Technical Report).  Key stakeholder considerations One of the factors at play in the systematic review decision, will be a desire to transfer ISO 13485 to the harmonised approach used in other ISO management system standards (see Annex SL and Annex SL Appendix 2 REV 4 of ISO/IEC Directives, Part 1 Procedures for the technical work Consolidated ISO Supplement — Procedures specific to ISO). Moving ISO 13485:2016 to the harmonised approach is achievable. A move to the harmonised approach would leave ISO 13485 closely aligned with the structure and content of other management system standards such as ISO 9001 and ISO 14001, a move that could be beneficial for organisations maintaining conformity to multiple management system standards. It would also make combined certification audits (by a certification body) feasible and/or easier. In order for ISO 13485 to remain valid ‘for regulatory purposes’ (e.g. ensure requirements are clear, specific, and require objective evidence to demonstrate conformity), it is likely that modifications to the standard text (of the Annex SL) would be required; the question is whether that would still be acceptable for all stakeholders? The likely number of modifications to the standard text of Annex SL could also increase the development time of the revised standard. At the time of the last systematic review in 2020, several key stakeholders expressed their concerns about the move towards the harmonised approach and called for time to allow ISO 13485:2016 to bed-in whilst other aspects of the medical device industry were still in a state of change. There was also a concern about maintaining alignment with an approach for which the medical device industry has no direct influence over the frequency of updates (e.g. updates to the ISO harmonised approach would be a trigger to revise ISO 13485 at the next review point). As already mentioned, ISO 13485:2016 holds a special place in the foundations of many medical device regulatory frameworks around the world. For example: EN ISO 13485:2016 / A11:2021 is harmonised for the EU MDR 2017/745 and IVDR 2017/746; ISO 13485:2016 is the basis for the Medical Device Single Audit Program (MDSAP) used by participating members Therapeutic Goods Administration (TGA) of Australia, Brazil’s Agência Nacional de Vigilância Sanitária (ANVISA), Health Canada, Japan’s Ministry of Health, Labour and Welfare (MHLW), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), and the U.S. Food and Drug Administration (FDA); ISO 13485:2016 is to be incorporated by reference by the US FDA in February 2026 as part of the amendments to 21 CFR 820; ISO 13485:2016 is leveraged for many guidance documents published by the Global Harmonization Working Party (GHWP) for use by its many members; EN ISO 13485:2016 is a designated standard in the UK for medical devices, active implantable medical devices and in vitro diagnostic medical devices. There are numerous other national regulatory frameworks that are founded on either the principles or requirements of ISO 13485:2003 and/or ISO 13485:2016. Several of the above (and more) were cited as part of the stakeholder feedback for the 2020 systematic review (e.g. from national committees, IMDRF, trade associations and the MDSAP RAC Chair). The US FDA’s incorporation of ISO 13485:2016 as part of the amendments to 21 CFR 820 is now official (it was still a ‘plan’ back in 2019) and other regulatory authorities may have plans involving ISO 13485 too. For example, we know that the European Union and the UK’s MHRA are both official observers to the MDSAP and Singapore’s Health Sciences Authority (HAS) have just recently been added to that list. The MHRA have openly been discussing the idea of utilising MDSAP certification as part of changes to the UK regulatory framework and amongst the recent calls for the urgent revisions to the EU MDR and IVDR there have been requests from industry for the inclusion of MDSAP within the EU framework. The three possible outcomes of the systematic review are confirm, revise or withdraw. At this stage, given the nature of ISO 13485 as summarized above, it is highly unlikely that there would be a vote to withdraw the standard, so I shall not dwell on that further. It comes down to confirm (i.e. retain with no changes) or revise (i.e. a new work item to review and rewrite ISO 13485:2016). Confirmation would leave the 2016 version untouched for the next five years. That is five more years for regulatory frameworks to align with, or get closer to, the requirements of ISO 13485:2016. This would support the aim of getting closer to global regulatory harmonization desired by the IMDRF and many national competent authorities, including a more robust foundation for the efforts around regulatory recognition and reliance. A potential downside to confirmation is that it would be another five years for ISO 13845:2016 to feel more out of touch with the industry, especially when it comes to technology related challenges as the use of artificial intelligence (AI), including machine learning (ML), in both medical devices and in software used within the quality management systems continues to grow. And if the harmonized approach changes further in that time, that is potentially another degree of separation between ISO 13485:2016 and its alignment with other management system standards, which could make it more challenging for organizations claiming conformity to ISO 13485 and other standards such as ISO 9001 or ISO 14001. Aside from switching to the harmonized approach, is there a need to revise the content of ISO 13485:2016? Perhaps. But whilst individually we all may wish for minor revisions to certain clauses of ISO 13485:2016 or the addition of a new requirement, or even the removal of a particularly troubling requirement, the consequences of a revision do need to be considered. Consequences such as: the time it would take to produce the revised edition, during which further changes in the industry may occur and the harmonized approach may change again, the need for organizations to direct resources to QMS updates, training and transition rather than developing new products and monitoring existing products on the market, the cost and duration of implementation for device manufacturers, service providers and conformity assessment bodies, the impact on regulations that are directly or indirectly linked to ISO 13485:2016, the uncertainty that occurs during transition periods, especially where conformity to ISO 13485 is a customer requirement or is leveraged as part of a regulatory reliance scheme. An important question in the confirm vs. revise decision, is “what is the overall benefit for making the changes if the standard is revised?” Would the improvements outweigh the pain and cost of the (non-exhaustive) consequences mentioned above? That is not for me to answer here, the purpose of this blog is to simply raise awareness of the systematic review and the considerations involved. Why is all of this relevant to you? Let’s start with an assumption, if you are reading this blog then you are involved directly or indirectly in the medical device industry. And if that is the case, then ISO 13485:2016 probably plays an important role in what you do, what your customers do, or what your clients or your suppliers do. Therefore, the future of ISO 13485 will have an impact on you or your organization at some level. Which factors are important for you and your organization? Regardless of whether you participated in the public survey, the systematic review is an opportunity to communicate with your national standards organization, either directly, via members of the relevant national mirror committee for ISO TC 210 or via other stakeholders such as trade associations. Here are some of the ways you can get involved and express your views on whether ISO 13485:2016 should be confirmed or revised: Identify the applicable national mirror committee for ISO TC210/WG 1 (e.g. NA 176-01-02 AA in Germany and CH210/01 in the UK) for your location and start a conversation on the topic. Ensure that those voting in the systematic review of ISO 13485:2016 on your behalf (e.g. your applicable national standards organization) are aware of your preferences and concerns related to the possible outcomes of the review (i.e. confirm/no changes, revise or withdraw). Engage with colleagues within your organization and peers within your networks to make them aware of the systematic review and their opportunity to express their views on the review of ISO 13485:2016. Engage with any trade associations or professional bodies with which you or your organization are affiliated and determine if they are establishing a position on the systematic review of ISO 13845:2016. #### Opportunity & Risk: Why we should open our minds to off-label use By Ed Ball, CEng, MIPEM, MIMMM – Manager, Intelligence & Strategic Execution Introduction   This blog on off-label use is the second part, following a blog where I discussed the ins and outs of intended use. I looked at the various definitions for intended use in widely applied regulations and standards, decomposed the intended use into its various structural components, described the critical role that the intended use has within all things medical device and discussed how the intended use will likely evolve and change over time. I warned that we should not think of the intended use as a single statement but rather a more complex specification for how we intend a specific medical device to be used. In April I presented at the 2nd International Conference on Medical Device Safety Risk Management in Amsterdam. My talk was about intended use, reasonably foreseeable misuse and off-label use. Why did I choose this topic? Firstly, because understanding and characterising the intended use of a medical device is so critical that I don’t think we can talk about it enough. Secondly, because I have noticed an increase in the discussions around off-label use, especially in the context of real-world data and EU requirements for post-market clinical follow-up (PMCF). So, What Is "Off-Label Use"?   To discuss off-label use, you first need to know what is ‘on-label use’ (that is not a phrase I want to stick). This is the intended use. Therefore if the intended use is the path, laid out in the device’s labelling and instructions for use, then off-label use is the deviation from that path. Now you would think there would be an official definition for off-label use. Of course there is. Where?  In at least one of our favourite standards? Nope. Obviously by the IMDRF? No, afraid not. In our most widely used medical device regulations? Third time lucky? No, again. The only ‘official’ place I could find an actual definition of off-label use was in the US regulation 32 CFR 199.2 which provides the definitions for the guidelines and policies for the administration of the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) for the Army, the Navy, the Air Force, the Marine Corps, the Coast Guard, the Commissioned Corps of the U.S. Public Health Service (USPHS) and the Commissioned Corps of the National Oceanic and Atmospheric Administration (NOAA). Just what you were expecting right? How Is It Defined?   This well-known US regulation defines off-label use (of a drug or device) as: A use other than an intended use for which the prescription drug, biologic or device is legally marketed under the Federal Food, Drug, and Cosmetic Act or the Public Health Services Act. This includes any use that is not included in the approved labeling for an approved drug, licensed biologic, approved device or combination product; any use that is not included in the cleared statement of intended use for a device that has been determined by the Food and Drug Administration (FDA) to be substantially equivalent to a legally marketed predicate device and cleared for marketing; and any use of a device for which a manufacturer or distributor would be required to seek pre-market review by the FDA in order to legally include that use in the device's labeling. The UK’s MHRA talk about off-label use in the context of advice for healthcare institutions and clinicians, warning of the safety risks and liability that come with such use. The MHRA do not however provide an official definition. Australia’s TGA provide their own online guidance on off-label use and it includes a simple definition as follows: 'Off-label use' is using a product for a reason not listed as one of the indications for use in the Australian Register of Therapeutic Goods (ARTG). Whilst this TGA definition is simple it is also misplaced in my opinion. For those paying attention to my last blog, indications is but one part of the intended use. Therefore off-label use can occur on other elements of the intended use other than the indications. Perhaps it is down to how TGA define intended use and indications? That is a rabbit hole for another day. In conclusion, my simplistic definition is “a use for which the device is not legally marketed, based upon the intentions communicated by the manufacturer”. Perceptions of Off-Label Use Off-label use is often seen as a negative thing. It is not uncommon for ‘off-label use’ and ‘user error’ (deliberate choice of ‘user’ there before anyone calls me out on it) to be used as defensive responses to incoming complaints about device failures or poor performance. Why do we see it in such a negative context? Just like the advice in the MHRA’s guidance, many hear off-label use and are immediately concerned with increased risks to patients and users, or about unproven effectiveness of the device, or even about increased product liability for the manufacturer (or for the healthcare professional, or their institution). Those with a more open, positive mindset may hear off-label use and think about opportunities to meet unmet clinical needs, to provide improved care options for patients, to improve user experiences and opportunities for future device development. It's crucial to consider both sides of this issue to manage this complex topic effectively. The Spark That Lit the Fire The trigger that made me think about off-label use more closely was the Team-NB position paper from 2022 “Data generated from ‘Off-Label’ Use of a device under the EU Medical Device Regulation 2017/745”. What was it that caused the spark? The logical narrative? The tidy formatting? The pretty logo in the header? All good guesses, but no it was this statement that really got me thinking: “Foreseeable misuse may be identified through usability studies or pre-market clinical investigation reports but it is often difficult for manufacturers to predict areas of future misuse…” The first part of that sentence suggests that we can identify ‘foreseeable misuse’ through usability studies or pre-market clinical investigations. This is true, but they are not the only weapons in our armoury. The second part of that sentence states that it is hard to predict reasonably foreseeable misuse. My stance is that in many cases, off-label use can be readily foreseeable, even in the pre-market development stages. To achieve this I don’t believe that we need fancy AI-enabled predictive models; we should be able to utilise the tools and methods that we currently have available, as well as channelling our inner 3-year-old and keep asking questions. Identifying Off-Label Use This will not come as a shock, but I am obviously going to come at this from a risk management perspective. Following ISO 14971:2019, one of our key steps in the risk management process is the risk analysis. To start this analysis, we document both intended use and reasonably foreseeable misuse of the device. But that’s not off-label use I hear you say! Wait for it. Figure 1 indicates the difference in scope of ISO 14971 and IEC 62366-1. Figure 2, also from IEC 62366-1, illustrates the links between the different types of use for a medical device. Neither mention off-label use, but both indicate that abnormal use is in scope of ISO 14971 and can thus either be part of the intended use or the reasonably foreseeable misuse. IEC 62366-1 provides some examples of abnormal use including the ‘conscious disregard for the contraindications’, which based on our previously identified definitions fits the bill for off-label use. MDCG 2023-3 Rev. 2 also states that abnormal use would include off-label use of a device. Figure 1. Illustration of the respective scopes of ISO 14971 and IEC 62366-1. Adapted from IEC 62366-1:2015 Figure D.1. Figure 2. Illustration of relationships between different types of use. Adapted from IEC 62366-1:2015+A1:2020 Figure A.4. By definition, reasonably foreseeable misuse can be foreseeable, meaning we can predict it based on human behaviour. It does not take a rocket scientist to look at the layout of the paths in Figure 3 to identify the potential for users of those paths to create the desire path that cuts the corner because the intended path directions are not optimal for the routine direction of travel. Figure 3. A desire path between concrete sidewalks at the Ohio State University (Image from https://en.wikipedia.org/wiki/Desire_path, By dankeck - https://www.flickr.com/photos/140641142@N05/52849400711/, CC0, https://commons.wikimedia.org/w/index.php?curid=131970058) We would typically start identifying reasonably foreseeable misuse before any usability studies or clinical investigations are commenced. Tools and methods for this prediction can include: Key Opinion Leader feedback: What do your expert users think? Customer feedback: Listening to what the customers really need, or what is missing from their treatment options. Brainstorming: Unstructured thinking through of the intended use and potential misuse scenarios. State of the art (SOTA) analysis: Analysing other treatment options for the intended use, analysing the intended use and contraindications of similar devices, consideration of the clinical context of the device and what other treatments and activities would be occurring in parallel or close proximity. PMS Data Analysis: Analyzing post-market surveillance data for instances of use error, reasonably foreseeable misuse and off-label use. Clinical Literature Analysis: Reviewing existing clinical studies and literature for reported cases of use error, reasonably foreseeable misuse, off-label use or indications of an unmet clinical need. Analytical techniques (e.g. task analysis): Logical step-by-step analysis of the discrete tasks involved with the use of the device and consider what could happen, e.g. considering the perception, cognition and action framing. Competitor analysis: Analysing the intended use and contraindications of their devices. If they have broader indications than your device, that is a sure-fire indicator that your device could also be used in those broader indications if they are seen by clinicians as equivalent devices. Usability Studies: Conducting formative and summative studies to identify potential errors. Exploratory clinical investigations: Conducting exploratory investigations may identify situations not anticipated by the designers and may highlight user needs or questions that were not previously anticipated. After you’ve gone through at least one of these methods, what do those results look like? Table 1 below provides some examples of the kind of situations the above methods can help identify before the product is launched to market. Element of intended useWhat we intend…But what if it is used like this?Intended medical indication(s)For repair of weak soft tissue in the abdominal wallProphylactically used to strengthen tissue around surgical incisionsIntended patient population(s)Adults (unspecified)- Paediatrics, neonates- Pregnant women- >70 years old- Different ethnicities- ComorbiditiesIntended part of the body or type of tissue applied to or interacted withIntact skin- Breached or broken skin- Nasal or oral mucosal surfacesIntended duration of use14 days- 25 days- 7 daysintended user profile(s)Unsaid <fit and healthy adult>- User with a prosthetic leg- Short / tall usersHealthcare professional- Lay personuse environment(s)A State-of-the-art clinic- Rural clinics- Domestic homesIntended lifetime of the device10 years- 14 years*Intended accessoriesOnly used with our accessory- Used with any accessory to handadjunctive devices &/or therapiesImmediate recovery period involves daily administration of medicine X- Used with medicine Y- Lower dose of medicine X- Less frequent doses of medicine XTable 1. Examples of off-label use (* See the MHRA’s post-market surveillance guidance where they discuss reasonably foreseeable use beyond the lifetime of the device, but have stopped short in giving the previous proposed term of ‘lifespan of the device’). By understanding these potential scenarios, manufacturers can better prepare for off-label use by making some important decisions. Pre-Market Decisions  With each of these instances of reasonably foreseeable misuse identified, product development teams have a decision to make. Adopt this likely use into the intended use, or keep it very much in the misuse category. If adopted, this aspect of the use needs to be added to the intended use (e.g. the use specification as per IEC 62366-1) and managed as a design change in the development project. Management of that change should include identification of any additional design input requirements to accommodate this aspect of use, any changes to existing design specifications (including information for use), any new hazards, hazardous situations, harms etc. to be considered in the risk analysis and any additional design verification and/or design validation work to generate the applicable objective evidence (e.g. laboratory testing, usability studies, clinical investigations, performance evaluation studies). If the identified misuse is still considered misuse (i.e. not adopted) then it should be determined whether any further risk control measures need to be implemented (e.g. identification of contraindications) and then subsequently verified as effective. As shown in Table 1, this is probably not a one-time thing. This will likely occur several times during the development of a medical device, and the intended use will be an iterative thing, with details added and excluded as decisions are made (Figure 4). Figure 4. Illustration of the iterative nature of the intended use Ultimately, we have to settle on a defined intended use for the purpose of regulatory conformity assessments and market launch. But it does not stop there. On the Lookout for Off-Label Use Once a medical device is on the market, there are numerous requirements for the monitoring of the device’s performance and safety. This includes monitoring for off-label use. Those use situations categorised as misuse in the pre-market phase, should now be monitored to some extent to determine whether they are occurring in reality, and if so, whether they are resulting in the predicted outcomes. This means that the post-market surveillance system should be designed in a way to be able to detect instances of off-label use. One way to achieve this, is to use the IMDRF’s adverse event coding framework within the complaints handling system, which includes a specific code for off-label use as part of the codes for investigation conclusions (Annex D). The description of off-label use in this IMDRF code (D1103) could be argued to be more practically useful than those definitions previously presented. However, in terms of the IMDRF’s codes, it is confusing because there are at least two other codes addressing specific instances of off-label use: Shelf Life/Expiration Date Exceeded Reuse of Single Use Device Another route to identifying actual instances of off-label use is through post-market clinical follow-up (PMCF) or post-market performance follow-up (PMPF). It is important these follow-up activities ask the right questions to help identify off-label use. Asking “Did you use the device off-label?” may not be the best way to gather the desired information. A third method could involve monitoring social media for information that indicates off-label use. This may not be logical or feasible for some devices, but should be considered for many devices that are long-term implants or require continuous use (e.g. a blood glucose monitor), where there may be various online groups for patients/users/carers to share stories and discuss ways to help manage their conditions etc. This may include untried suggestions of how a device could work better (e.g. “despite what it says in the instructions, I’ve found that it works better if I place the sensor on my upper thigh rather than my upper arm”). This kind of feedback can shed light on common complaints that are never reported directly to the manufacturer, as well as instances of off-label use and/or promotion of off-label use by individuals. Another option is to look for off-label use during literature searches within post-market surveillance activities. This may require specific search criteria related to the nature of the off-label use (e.g. citing the specific contraindicated indication or patient population). Post-Market Decisions When off-label use is identified in post-market, we have another key decision point. But before that, there is an often-overlooked action. If there is clear off-label use, e.g. clear disregard for contraindications, or working outside of the defined intended use, then the device manufacturer should be clear to the user that they have used the device off-label. Without that communication, regardless of what decisions come afterwards, the manufacturer could be considered to be tolerating the off-label use and bypassing the applicable conformity assessment. It could also have implications for product liability should any patient and/or user subsequently be harmed as a result of such off-label use. For clarity, if there are instances of actual use of the device in areas where the intended use has been poorly defined for the user, this may not be considered off-label use. Recalling the simplified definition from earlier, it is the use as intended by the manufacturer that is then communicated to the users. If the finer details of the intended use are not defined or communicated to the end-users, they cannot be accused of using the device off-label. Instances of actual off-label use may: signify an unmet clinical need, e.g. an underserved clinical condition or a small patient population; highlight confusion between similar devices with differing indications and contraindications; indicate a predictable response to the removal of a similar device from the market, leaving a gap in the market for a specific intended use; represent a clinician’s decision on how best to treat their specific patient with the equipment options that they have available. There should be a check of the risk management file to determine whether the off-label use was anticipated or not. If not, why not? Does it reflect a gap in the methodology used for risk analysis, or in the contextual awareness of the development team? If this type of off-label use was anticipated, were there any controls in place to address this use? If so, how effective were they? These are all sensible questions to ask yourself (before your competent authority asks them of you!). Ok, back to decision time. We now have to decide what to do with the identified off-label use. Maybe it is a one-off, maybe it is a trend of systematic off-label use. Either way, we need to plot our next steps. Option 1 is to embrace this off-label use and adopt it. This would require a change management activity to update the intended use and then implement that change accordingly, possibly requiring additional regulatory conformity assessment(s) before communicating the change to customers and users. In many cases, this would require the gathering or generation of additional objective evidence to support this extended intended use (e.g. a new patient sub-population, or a new indication). Ensure that this is managed correctly as design creep without appropriate regulatory ‘approval’ is a known issue, especially witnessed by the FDA in the US. Option 2 would be to stick with the current boundaries of intended use and maintain the stance that this type of use is off-label use. This becomes more risk focused and depends on the risk associated with the off-label use. This means risk both in terms of the occurrence of such use and the potential consequences, either in harm or ineffective treatment. Are the existing risk control measures sufficient? Do these real-world events change the acceptability of the risk associated with the off-label use? Are further risk control measures necessary and if so, what form will they take and how will you measure their effectiveness? It may be that the intended use was too vague and the off-label use was not clearly prohibited in the instructions for use, or it was determined to be unlikely to occur; either way action (e.g. now clearly stated as a contraindication) may be warranted. Conclusion Off-label use is a complex but fascinating aspect of medical device safety. It is not something to be inherently scared of. By understanding the intended use, identifying foreseeable misuse, and analysing the data, manufacturers can make informed, evidence-based pre- and post-market decisions. It's all about balancing opportunities with risks to ensure the best outcomes for patients and users. This is especially important when it relates to off-label use that falls into the ’orphan’ category (e.g. an orphan patient population or indication), and there can be an inclination to contraindicate, rather than adopt, as the quicker solution. Related Next Steps Go back and check out part 1 of this blog: Intended Use: Foundation stone, guiding light or just a box to tick? Revisit our RQM+ Live show from 2023 “Beyond Indications: Managing Off-Label Use for Safety and Compliance” Need help with anything off-label use? Does your risk management process need assessing to ensure that it supports the identification of off-label use? Unsure whether you have sufficient clinical data to support specific indications? Is your post-market surveillance system capable of detecting off-label use? Need to optimise your PMCF strategy to ensure that you can gather clinical data on off-label use? Contact us to discuss how we can support your efforts. Bibliography:  For those interested in diving deeper, here are some key references: ISO 14971:2019 Medical devices — Application of risk management to medical devices ISO 13485:2016 Medical devices — Quality management systems. Requirements for regulatory purposes IEC 62366-1:2015/Amd 1:2020 Part 1: Application of usability engineering to medical devices EU MDR 2017/745 FDA Guidance on Human Factors and Usability Engineering management systems. Requirements for regulatory purposes ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO 14971 ISO 20417:2021 Medical devices — Information to be supplied by the manufacturer ISO/TR 20416:2020 Medical devices — Post-market surveillance for manufacturers Applying Human Factors and Usability Engineering to Medical Devices (FDA, 3 Feb 2016) Guidance on applying human factors and usability engineering to medical devices including drug-device combination products in Great Britain (MHRA. V2, Jan 2021) AAMI TIR50: 2014/(R)2017 Technical Information Report Post-market surveillance of use error management Purpose and Content of Use-Related Risk Analyses for Drugs, Biological Products, and Combination Products Guidance for Industry and FDA Staff (FDA, Draft, July 2024) IMDRF/GRRP WG/N47 FINAL:2024 (Edition 2) Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices Data generated from ‘Off-Label’ Use of a device under the EU Medical Device Regulation 2017/745. (Team-NB, 5 Oct 2022) Off-label use of a medical device (MHRA, 1 July 2023) Understanding regulation of off-label use of medical devices (TGA, 23 Sep 2024) Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products Questions and Answers (FDA, Jan 2025) Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (FDA, draft, Dec 2011) Off-label Use of Medical Devices (Medical Device Network, May 2017) IMDRF/Registry WG/N46 FINAL:2018 Tools for Assessing the Usability of Registries in Support of Regulatory Decision-Making IMDRF/NCAR WG/N14FINAL:2017 (Edition 2) Medical Devices: Post-Market Surveillance: National Competent Authority Report Exchange Criteria and Report Form MDCG 2023-3 Rev. 2 Questions and Answers on vigilance terms and concepts as outlined in the Regulation (EU) 2017/745 and Regulation (EU) 2017/746 (Jan 2025) For further reading - 5 Key Elements of GMP in the Food Industry #### Overcoming Pain-Points in MedTech Clinical Trials for Brain Health Devices MedTech innovations in brain health are paving the way for new interventions for conditions such as Alzheimer’s disease, Parkinson’s disease, depression, epilepsy, and chronic pain. From neuromodulation implants to AI-driven cognitive therapy platforms, these technologies hold immense clinical promise. Yet demonstrating their safety, efficacy, and usability through clinical trials is uniquely demanding. Clinical trial professionals and MedTech sponsors in the neurology space often face operational, ethical, and regulatory hurdles that are more complex than those in other device categories. This article explores the most common pain-points in brain health device trials—and how strategic support from specialized partners like RQM+ helps sponsors navigate them effectively. Pain-Point 1: Recruitment and Retention in Neurologically Defined Populations Enrolling the right participants remains one of the most persistent challenges in brain health trials. These studies often require individuals at specific stages of neurological disorders—such as early-stage Alzheimer’s, drug-resistant epilepsy, or treatment-refractory depression—making recruitment both narrow and complex. Strategies to address this challenge: Utilize electronic health records (EHRs), cognitive screening databases, and memory clinics for precise patient targeting Work with trusted advocacy organizations to help support patient recruitment, and provide clinical trial awareness, education, and community engagement  Implement decentralized trial components (e.g., telehealth visits, eConsent) to broaden geographic reach Engage both patients and caregivers through tailored communication and flexible scheduling Pain-Point 2: Measuring Subjective, Variable Endpoints Brain health devices often target domains such as mood, pain, or cognition—areas where outcomes are inherently subjective. This variability complicates data consistency and regulatory confidence. Solutions for endpoint optimization: Use validated instruments for neuropsychological and cognitive function measurement Employ digital biomarkers and passive data collection where applicable Combine subjective primary outcomes with objective secondary endpoints to reinforce claims Pain-Point 3: Ethical and Regulatory Complexity Trials involving the brain demand heightened ethical oversight. Invasive interventions, placebo controls, and vulnerable populations increase the need for transparency, safeguards, and alignment with global regulatory frameworks like the FDA’s De Novo pathway or the European Union’s MDR/IVDR. Recommended approaches: Pursue early engagement with regulatory authorities and ethics boards Design patient-centric informed consent procedures adapted for cognitive limitations Leverage experienced regulatory consultants to mitigate submission risks Pain-Point 4: Device-Specific Technical and Operational Barriers Unlike drugs, brain health devices introduce layers of complexity—from hardware durability and software interoperability to user training and data integration. Mitigation strategies: Conduct comprehensive verification, validation, and usability testing pre-trial Standardize training programs for investigators, site coordinators, and patients Deploy centralized platforms for real-time data capture, remote monitoring, and device feedback Ensure the trial team has adequate availability to support sites when questions arise, with both on-site support as well as remote Pain-Point 5: Managing Patient Safety and Adverse Event Reporting With interventions directly impacting neurological function, safety must be rigorously managed. This includes not only the monitoring of device effects but also the mental well-being of participants. Best practices include: Establish independent Data Safety Monitoring Boards (DSMBs) for oversight Define clear AE reporting pathways and escalation plans Include Clinical Endpoint Committees to review and adjudicate events in real-time to provide an independent assessment of events, and support the sites in reporting requirements Partner with CROs experienced in neurology and high-risk populations How RQM+ Supports Brain Health Device Trials RQM+ is The MedTech CRO and delivers a fully integrated suite of clinical trial services specifically tailored for MedTech innovators in the brain health sector. Offerings include: Regulatory strategy development and pre-submission consulting Protocol design focused on neurological endpoints and patient engagement Targeted recruitment strategies using cognitive disorder networks and digital tools Real-time data systems that ensure clean, actionable results Comprehensive risk management, including safety oversight and remote monitoring With flexible resourcing and access to multidisciplinary scientific experts, RQM+ ensures that trials maintain momentum... even when facing unforeseen complications. Executive Insights: The Strategic Value of Expertise For executives navigating MedTech development in neurology, these pain-points are more than operational snags—they’re strategic threats. Slow enrollment, unvalidated endpoints, or regulatory noncompliance can derail innovation and investor confidence. Working with a full-service partner like RQM+ mitigates these risks by aligning trial execution with scientific credibility and market-readiness. Find Support for MecTech Clinical Trials Brain health trials demand precision, foresight, and agility. When these studies are well-supported and strategically designed, sponsors not only overcome obstacles—they gain competitive advantage. RQM+ combines clinical operations acumen, regulatory foresight, and deep neurological expertise to help MedTech leaders bring transformative brain health solutions to patients: safely, swiftly, and successfully. Contact us today if you are looking for support with MedTech clinical trials. #### Polymer Failure Analysis with Jordi Labs, an RQM+ Company Failure analysis is a critical field used to detect chemical and mechanical defects in polymeric materials, pinpointing the factors that have contributed to or directly resulted in product failure. This analytical discipline plays a pivotal role in enhancing the properties and value of polymer products. In instances of severe product failure, failure analysis is instrumental in determining liability, especially in cases involving hazardous device failures. The failure analysis process typically commences with a forensic evaluation of the failed component to ascertain the root cause of flaws. This initial step is crucial in guiding the selection of the most appropriate analytical methods for assessing the level of failure. It aids in informing corrective actions, ensuring that the failed product was manufactured in accordance with the required certifications, and aims to prevent future failures. What Causes Polymer Failure? Both internal (material properties) and external (environmental) factors may contribute to the degradation of polymeric products. However, performing failure analysis focuses on identifying the inherent cause of failure within the product itself. For instance, external thermodynamic or chemical stress can lead to the wear and eventual breakdown of polymers. Failure in response to specific strains is anticipated and may be deemed acceptable from a liability standpoint. Nevertheless, if a polymer fails to withstand strains within the predefined parameters of its application requirements, failure analysis is tasked with uncovering the root cause. Common root causes of polymer failure encompass design flaws, the use of inappropriate raw materials, and the presence of contaminants within the product. These issues underscore the importance of rigorous quality control in manufacturing processes. This blog post will delve into some of the prevalent analytical techniques for performing failure analysis in greater depth. Understanding Failure Investigations Among the key aspects of failure investigations are the data collected regarding the failed component's chemical composition and physical properties. Analytical chemists employ various analysis techniques, depending on the type of failure and polymer chemistry at play to discern the root cause. Through these sophisticated analytical methods, experts can evaluate the impact of manufacturing processes, environmental factors, and the selection of raw materials on the integrity of the product. The techniques employed can then be used, depending on results, to implement more robust quality control measures ensuring the same failure is not repeated. The insights gained from failure investigations are invaluable in refining the design, selection of materials, and manufacturing processes of polymeric products, ensuring they meet the rigorous demands of their applications. Failure Analysis Methodologies Gel Permeation Chromatography Gel permeation chromatography (GPC) is most commonly used to determine a sample material's polymer molecular weight (MW) by standardizing its physical properties against industrial benchmarks. It is also used to assess material degradation for failure analysis of polymeric products by dissolving a small sample of the failed component in a solvent and assessing the molar mass of the analyte through chromatographic measurement. This generally requires an understanding of the molecular weight distribution of the successful end-product for comparison. Stereo Microscopy Stereo microscopy is a nondestructive method of failure analysis that allows analysts to assess cracks in the surface of solid polymer products directly. It provides low magnification of an analyte material, with a magnifying range of 35 – 90x and two varying viewing angles for each eye.  Failures related to surface defects or other mechanical problems can be assessed.  For brittle materials, crack propagation analysis can provide further insight into the origin of failure. FTIR-Microscopy FTIR microscopy enables analysts to assess the heterogeneity of sample materials to screen for compositional differences that could have contributed to mechanical failure. Small phase inconsistencies can be detected through microscopic analysis of surface molecules excited by infrared light. The absorption of light is recorded to create a chemical map of the surface composition and identify variations in the sample bulk. Mass Spectrometry Mass spectroscopy refers to a collection of techniques that measure the mass of individual chemical species. It is one of the most important methods of chemical analysis because the mass of a molecule is one of its most defining characteristics. Mass spectroscopy can be used to identify unknown chemicals and to determine their amount. This makes mass spectroscopy a very useful tool for forensic analysis as it enables the determination of the ingredients in a sample and allows comparisons of the amounts. Mass spectrometers are highly sensitive instruments routinely capable of detection of chemicals in the parts-per-billion concentration range. Typical examples of mass spectroscopy techniques include liquid chromatography-mass spectroscopy (LCMS), gas chromatography-mass spectroscopy (GMCS) and pyrolysis mass spectroscopy (PYMS). Jordi Labs, an RQM+ Company Service Labs is uniquely prepared to provide expert failure analysis to support corrective actions or to inform liability cases. With over 30 years’ experience of product failure analysis, we can accurately represent robust scientific data in an easy-to-understand manner. If you would like any more information about our failure analysis methods, please do not hesitate to contact us today. Be sure to check out our Knowledge Center for more resources related to this topic! #### Preparing for the Phase-Out of PFAS in MedTech Manufacturing Major per- and polyfluoroalkyl substances (PFAS) suppliers are beginning to exit the market due to significant environmental, health, regulatory, and legal concerns. That’s mostly a good thing! While PFAS are used in an incredible array of consumer products, including medical devices and in vitro diagnostics, they can pollute the environment and endanger health. Globally, regulatory bodies are responding to these environmental and health concerns. The European Union is leading the charge, with Denmark, Germany, the Netherlands, Norway, and Sweden proposing that PFAS be restricted under the REACH regulation. America is also taking strides toward minimizing the use of PFAS. The US Environmental Protection Agency, for instance, recently ruled that PFAS are subject to the same reporting requirements as other chemicals of special concern. These regulatory changes reflect a growing global consensus on reducing PFAS usage, with countries like Canada, Australia, and several Asian nations actively engaging in the discussion. As the world is concerned about PFAS and crucial suppliers are ceasing the manufacture of PFAS, MedTech manufacturers must find a way to adapt and innovate.  In this article, we unpack steps manufacturers can take to phase out PFAS and safeguard their product lines and profitability. For an even deeper dive and the ability to ask us your own questions, please RSVP for our January 2024 expert panel event. To start, let’s explore how dwindling supplies may accelerate the timeline to abandon FPAS. Will PFAS Supplies Dwindle by 2025? Along with regulations, supply chain issues will play a critical role in removing PFAS from use. 3M, a leading manufacturer of PFAS, will completely stop manufacturing the chemical by 2025. This decision came in the wake of mounting legal challenges. In June 2023, for instance, 3M settled approximately 300 lawsuits for $10.3 billion. DuPont, another leading PFAS manufacturer, is facing similar legal woes.  Collectively, DuPont and 3M are facing over 4,000 lawsuits by states and municipalities and another 6,000 personal injury lawsuits — all due to their PFAS manufacturing. These lawsuits reflect the increasing legal and financial pressures associated with PFAS production and use. The response from 3M is just a precursor to a larger industry trend. As regulatory bodies tighten restrictions on PFAS, other manufacturers are likely to follow suit, further constricting the supply of these materials. The dwindling PFAS supply will have a knock-on effect, limiting the availability of parts that make use of PFAS. This scenario poses a challenge for MedTech companies, compelling them to reassess their material sourcing strategies and hasten their search for sustainable and compliant alternatives.  So, when should MedTech secure a PFAS alternative? 3M gives us a clear deadline: by 2025. Steps for Phasing Out PFAS The move away from PFAS represents a significant shift in MedTech, especially as these substances have been a cornerstone in the design and manufacture of so many medical devices.  Along with being resistant to heat, water, and oil, PFAS chemicals do not degrade easily. A viable substitute will need to have similar properties and their use should, ideally, enhance and not detract from device quality. Here are five key steps for phasing PFAS out of your products: Perform a PFAS Gap Assessment — the first step involves a comprehensive assessment of existing product lines to pinpoint where PFAS are used. This detailed analysis requires collaboration with suppliers and a thorough understanding of the material composition in the manufacturing process. Lab testing may be needed to verify the information given by suppliers. Identify PFAS Alternatives — manufacturers must consider potential redesigns to accommodate new materials while maintaining device functionality and performance. Identifying suitable alternatives requires exploring various sources and materials, and understanding their implications in terms of device design, application, and patient safety. Testing and Validation — once alternatives are identified, the focus shifts to rigorous materials testing and validation. This includes biocompatibility testing, chemical characterization, and ensuring the new materials meet the technical and safety standards for medical devices. Documenting these tests is crucial for submitting complete safety evaluations. Design and Implement the Right Regulatory Strategy — successfully finding a suitable source to replace PFAS in product materials demands a strategic approach to regulatory compliance. This includes preparing and submitting detailed documentation to regulatory bodies and aligning with global regulatory changes, such as the significant updates in the EU. Understanding and navigating these regulatory landscapes are essential for a smooth market transition. Strategic Planning and Execution — effective project management is key to a successful transition. Manufacturers need to adopt best practices for planning and execution, ensuring minimal disruption to supply chains and operations. This step involves proactive risk management, contingency planning, and stakeholder communication to maintain continuity and competitiveness in the market. Navigating a Future Without PFAS Replacing PFAS with a suitable alternative requires careful navigation, informed decision-making, and strategic adaptation. The complete phasing out of PFAS will take time — enough to accommodate the product life of most current designs. However, PFAS manufacturers will likely continue exiting the market. Another issue is that PFAS’ unique properties lack a current substitute. The challenges ahead are considerable, but they also present an opportunity for innovation and leadership in developing safer, more sustainable medical devices. As a full-service CRO, RQM+ can help your MedTech company adapt to a future without PFAS. With over 40 years of expertise in polymers, including a decade of focused experience with PFAS materials, we understand the unique challenges and intricacies involved in replacing PFAS in medical devices. Our Lab Services team can help you with chemical characterization, mechanical property evaluation, and ensuring the biocompatibility of alternative materials. Of course, transitioning from PFAS is as much a regulatory challenge as it is a technical one. Our Regulatory Consultants offer support in developing documentation, aligning with regulatory agencies' expectations, and ensuring that the transition to PFAS alternatives is smooth and compliant. Speak with our experts to find out how we can support you in substituting PFAS in your products. Exclusive Opportunity to Learn More About the PFAS Phase-Out Gain a deeper understanding of the PFAS phase-out and how it impacts your operations. RSVP for our free expert panel: Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers. RSVP today to hear a panel of MedTech experts share their roadmap for overcoming PFAS challenges. View Webinar #### Product Deformulation: A Step-by-Step Guide to Reverse Engineering Chemical reverse engineering is an extremely valuable process for those looking to protect their intellectual property from manufacturing issues or patent infringements. It is also deployed to help manufacturers maintain a competitive edge through targeted product analysis. Each of these goals can be realized through product deformulation; the process of analytically breaking substances down so their constituent parts can be identified and quantified. Product deformulation services vary by objective, but also by capability. Few chemical reverse engineering labs have the toolset available to deconstruct complex product matrices and extract both their minor and major constituents to deliver conclusive, precise results. At RQM+ Lab Services, this sort of complete product deformulation is one of our specialities. This article aims to serve as a step-by-step guide to our product deformulation service. Given the broad spectrum of potential areas of application, it is difficult to narrow down the chemical reverse engineering process to a single workflow. However, we will refer back to a relevant case study to offer some more concrete insights into our uniquely expert service. Initial Consultation The RQM+ approach to product deformulation is consultative from end-to-end. We begin with an initial, client-led discussion in which we will determine the scope and main aims of the project, whether you are merely carrying out investigatory work or are seeking support for litigation purposes. Once this is established, our team will discuss the best methodology for the project and use this intended workflow to come up with a written quote. For example: A client of ours wanted to investigate the chemistry of a polymeric urinary drainage bag through complete product deformulation. This was well within our expansive capabilities, so we submitted a quote and accepted submitted samples for analysis. Analysis of Samples As mentioned above, it is partly the toolset that hinders some product deformulation labs from offering a truly complete reverse engineering service. The RQM+ Lab Services team has decades of expertise in all areas of analytical chemistry with a world-leading testing facility available to apply that knowledge to custom deformulations. This enables us to pull apart even the most complex product matrices with maximum analyte retention to ensure that all results are truly representative of submitted samples. Returning to the case of the urinary drainage bag, the customer benefitted from our particular expertise in polymer chemistry. We passed the sample through seven different testing paradigms to gain a complete chemical profile based on mass spectral, thermal, and nuclear resonance properties. Delivery of Results Once we are satisfied that we have acquired a full chemical profile, we deliver a complete report summarizing our findings alongside a list of individual results per testing methodology. This instils absolute confidence in our results. We also close out our product deformulation service with a final consultation where we discuss actionable takeaways from the report. These vary depending on the underlying goal of the study, but typical next steps include product refinement, manufacturing scale up, or—in instances of product infringement—expert support through the litigation process. Interested in chemical reverse engineering? Contact a member of the RQM+ Lab Services team today to discuss any objectives you have in mind and we would be happy to setup an initial consultation with you. #### Product Deformulation: Reverse Engineering with RQM+ Lab Services Product deformulation is a complex analytical process designed to uncover the specific chemical identity of finished goods. Chemists take the product of interest, break it down into its constituent parts, separate those into distinct entities, then analyze both the major and minor components present. Done correctly, this will yield a complete profile or “ingredients list” of all substances in the system. Additional consultation work can be provided to aid in reformulation and to identify the process used to develop the finished article. Obtaining an equivalent product requires not only the correct ingredients but the correct manufacturing process. RQM+ Lab Services has years of experience providing product deformulation services with a range of underlying objectives. Whether you need to investigate claims of patent infringement to protect your intellectual property or are looking to innovate your products as part of a new research and development (R&D) cycle, we can provide the expertise and the tools necessary to achieve the right results. Often referred to as reverse engineering, product deformulation can be as complicated and intensive as new product development. This is how the RQM+ team typically approaches it. How do you Reverse Engineer a Product? When we come to reverse engineer a system as part of a product deformulation service, we always begin with an initial consultation. An experienced RQM+ Lab Services chemist will discuss your objectives and start building a bespoke plan based on the nature of your samples. As there is essentially no limit to the substances that can be deformulated, there is no individual sequence of methods fit for all purposes. There will even be significant variations between materials of similar types. Polymers are a great example of this. Polymer deformulation is one of the most complicated forms of reverse engineering given the rich variety of plastic materials used in manufacturing today. These can take various forms (amorphous, liquefied, semi-solid, solid, etc.) and likely comprise myriad underlying monomers that can dramatically impact device performance – even when present at trace levels. This explains why the initial consultation is so critical. Your consultant will prepare a preliminary quote based on our understanding of the task at hand, which includes the full scope of our analytical testing capabilities and the delivery of fully articulated results. Once we have received your samples, the RQM+ Lab Services team will put the finished article through a sequence of tests to uncover its full chemical identity and determine how the individual constituents work in tandem. This typically involves a series of high-technology tests such as nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography-mass spectrometry (LCMS), gas chromatography-mass spectrometry (GCMS), gel permeation chromatography (GPC), and so on. In a single product deformulation run where the finished product was a polymeric medical bag, we leveraged seven different analytical techniques to develop a complete profile of the finished article.Afterward, the team will write-up their full results and conclusions in a robust yet easy-to-understand report, providing the exact insights that you set up in the initial consultation. Our product deformulation service is essential for anyone looking to enhance their product development cycle by gaining competitor insights, helping to benchmark quality, or to understand root causes of failure. RQM+ Lab Services has also been called upon to carry out product deformulation for litigation purposes.If you would like more information about our industry-leading reverse engineering service, simply contact a member of the RQM+ Lab Services team today. #### Protein Characterization, Identification & Purification Protein characterization is an incredibly broad field of study that encompasses a wide range of analytical methods and techniques. Although biochemists have made enormous strides in protein analysis, the process of identifying and purifying novel proteins remains a daunting task. This is mainly due to the lack of a one-size-fits-all solution for macromolecules with radically different aggregation states, charges, sizes, structures, and so on. The sheer breadth and complexity of protein characterization stem from the seemingly infinite pathways for protein expression. Consider this: All proteins are composed of chains of the same 21 amino acid residues of varying concentrations that may assemble in virtually endless arrangements. They can then be folded into three-dimensional (3D) structures that further vary in size. Complicating the protein characterization process further is the fact that they are never present in isolation. A single cell may contain as many as 10,000 different proteins. So, how do biochemists even begin to conduct protein analysis and characterization? Purifying Proteins To accurately characterize a single protein, chemists must first isolate it from a sample via purification and identify it by any number of defining characteristics. As mentioned, biochemists use a wide range of analytical methods – ranging from the routine to the experimental – to carry out protein characterization. Obtaining proteins for analysis begins when a sample is selected and fractionated. For instance, cells can be lysed and the desired sample material is extracted through differential centrifugation, where an increasingly pure supernatant is separated from larger sample debris. Even after multiple passes in a centrifuge, the supernatant is likely to contain thousands of distinct proteins. The protein of interest is purified by subjecting the sample to a separation method based on inherent chemical, electrical, or physical properties. Chromatography (affinity, ion-exchange, gel-filtration, HPLC, etc.) is one of the most common technologies used in protein purification as it allows for highly-selective separations of sample material based on various characteristic properties. Identifying Proteins Once a highly pure protein has been acquired, biochemists can then begin to characterize its composition, structure, molecular weight, purity/impurity, and so on. These objectives are often interlinked and are best accomplished in specific orders. For instance, the molecular weight of a protein chain is predicted based on the amino acid composition, which are determined by chemical methods. To chemically determine the precise amino acid sequence of proteins, its peptide backbone is cleaved using one of a number of potential methods such as tryptic digestion, where residues are sequentially cleaved from the protein chain and identified via high-pressure liquid chromatography (HPLC) and mass spectrometry. This is the most commonly used method for chemically-identifying the sequence of an individual protein. This is just one example of how proteins are identified and what is learned about their chemical structure. Other examples include: Molecular weight; Aggregation state; Spectroscopic characteristics; Purity/impurity; Homo- and heterogeneity; Extinction coefficient (molar absorptivity). Protein Modifications (glycosylation, PEGylation, etc.) At RQM+ Lab Services, we provide protein characterization and analysis using a suite of established tools. If you have unique protein analysis needs and think you might benefit from our support, simply contact a member of the RQM+ Lab Service team today. #### Quick Guide to Medical Device Standards: ISO Standards and Beyond In the regulatory world, standards are essentially recommended processes that have been developed by subject matter experts with the aim of describing the best possible way to meet an end goal. For example, quality management standards are designed to improve efficiencies and avoid product failures. Similarly, risk management standards are designed to help organizations plan for the unexpected and ensure operational continuity. These are just two common examples of the many application standards for medical device manufacturers.   The International Organization for Standardization (ISO) sets global standards for quality and risk management for a broad range of products and businesses. Likewise, the International Electrotechnical Commission (IEC) sets international standards for all electrical, electronic, and related technologies. In general, ISO concentrates on controls for materials and processes, and IEC concentrates on the manufacturing and testing of products.  Standards cover a broad range of business and technology types, including medical devices, IVDs, and the electronics and software that accompany them. Compliance and certification are technically voluntary in many cases, but ISO is considered the gold standard and state of the art, so medical regulatory bodies often use it as a benchmark for regulatory compliance. Understanding the most commonly used IEC and ISO standards for medical devices is critical for maintaining compliance with global regulations.    Most Common Standards for Medical Devices and IVDs It’s up to manufacturers to determine which ISO standards apply to their business and products. In the U.S., the Food and Drug Administration lists the standards they strongly recommend for design and testing by product code. The standards that are listed under a regulation must be addressed somehow. Manufacturers must either comply with an existing standard or demonstrate that they have developed adequately validated test methods. Companies don’t necessarily need to demonstrate full compliance to receive clearance, but if there are any deviations, the company has to provide additional justification for how the purpose of the standard is still addressed.  European harmonized standards can be found on the Europa site. However, as noted below, this isn’t as straightforward for MDR and IVDR as it was for MDD and IVDD because there are currently no harmonized standards under MDR and IVDR. Some of the most common reference standards for device manufacturers to follow include: ISO 13485, which is the standard for medical device quality management systems. ISO 13485:2016 is the most current version, and it’s also harmonized in Europe. ISO 14971, which is the standard for medical device risk management. The most current version is ISO 14971:2019, but it isn’t yet harmonized in Europe. ISO 9001, which is the standard for business quality management systems, and the most current version is ISO 9001:2015.  ISO 62304, which is the standard for software used in medical devices, and ISO 62304:2006 is the most current version.  ISO 10993, which has 23 parts, is the standard for biological evaluation of medical devices.  ISO 15223, which has two parts, is the standard for symbols to be used with medical device labels, labeling, and information to be supplied. ISO 11135, which is the standard for ethylene oxide sterilization of medical devices, and ISO 11135:2014 is the most current version.  ISO 11137, which is the standard for sterilization of medical devices using radiation.   ISO 11607, which is the standard for sterilized product packaging for medical devices. IEC 60601, which is published by the IEC. This standard applies to the safety and essential performance of medical electrical equipment. Every country has a different version, and devices must comply with the standards that apply in each market. These are some of the most commonly used standards for medical devices, but this isn’t an exhaustive list, and the standards you apply will depend on the product features.  Benefits of ISO Compliance and Certification Although compliance with ISO standards isn’t always mandatory, and certification may not be required, there are many benefits to conforming to the applicable standards, including: Better quality management systems  Certification forces you to make process improvements, which ultimately adds value to your business.  Fewer audit findings and inspection deficiencies  FDA auditors and notified body reviewers will have fewer questions and find fewer issues if you are in ISO compliance for quality and risk management. Patient safety  This is the primary goal for both regulators and manufacturers. Conforming to ISO standards helps reduce quality issues and protect patients. Credibility  ISO compliance demonstrates that your business conforms to internationally recognized standards, which lends credibility to your brand among regulators, patients, and healthcare providers.   More efficient regulatory processes  When you comply with standards, FDA and notified bodies know you have properly tested products and processes, which helps streamline approvals, audits, and inspections.  Proven approach  Using standards whenever possible ensures that you are implementing tried-and-true systems and technology. This also helps improve efficiency because you can follow existing recommendations.  Principles of Harmonization When ISO standards for medical devices are harmonized for Europe, they are designated with “EN” in the title. For example, EN ISO 14971:2012 is the European harmonized version of ISO 14971:2007. In many cases for the standards that are relevant to medical devices, the EN version of the standard has the same content as the ISO standard with the addition of appendices that detail the relationship between the standard and the European Directives (the MDD, AIMDD, and IVDD). However, with the implementation of MDR and IVDR, no ISO standards have yet been harmonized to these regulations. What does this mean for device manufacturers when submitting technical documentation for review? We have seen that notified bodies are referencing the requirement for complying with standards that are considered state of the art. This is being interpreted as the most recent version, which isn’t necessarily the harmonized one. Therefore, the best practice is to stay compliant with the latest versions of standards as they are released to reduce review time and keep your products on the market.  It’s also important to note that the U.S. and EU have different requirements when it comes to staying current with standards. In the U.S., manufacturers must continue to comply with the standard that was applicable when the device was approved. There is no requirement to stay current as standards evolve unless there have been design changes. In the EU, manufacturers must stay compliant with the most recent versions of the relevant standards as they become available. Processes must evolve with standards regardless of when products were approved.  Advantages of RQM+  RQM+ offers support for compliance with IEC and ISO standards for medical devices in multiple ways. We constantly stay abreast of global regulatory requirements and the most current standards. Our expert team can help you: Identify required or recommended standards based on your device. Translate the requirements into understandable language for product development teams. Provide rationales and justifications for portions that don’t comply. Perform mock audits to identify gaps and weaknesses. Develop a strategy to address weaknesses.  Provide tactical implementation to achieve and maintain compliance. RQM+ is also ISO 9001:2015 certified, so we understand the benefits of participation and know what it takes to stay compliant. Contact us today.  #### R&Q Acquires Maetrics to Form the Largest Medical Device-Focused Regulatory and Quality Consultancy We are proud to announce that we have acquired Maetrics, a leader in life sciences quality and regulatory consulting. Check out the full press release below or visit our RAPS Convergence 2020 announcement page for more information. MONROEVILLE, Pa. — September 10, 2020 — Regulatory and Quality Solutions LLC (R&Q)—a leading provider of regulatory and quality consulting services for medical devices, in vitro diagnostic devices (IVDs), and combination products—today announced that it has acquired Maetrics LLC, an international leader in life sciences quality and regulatory consulting. Together, the two organizations form the largest agile and highly scalable consulting firm dedicated to their combined focus areas in the life science industry. "R&Q’s vision has always been to become the worldwide leader in providing full-service regulatory and quality solutions to the medical device and diagnostic industries,” said the company’s President, Maria Fagan. “Our exceptional business-balanced solutions and leadership have been key to accelerating the success of life science companies and ultimately improving the lives of people across the globe. We’re excited to take a critical step toward achieving our vision by adding Maetrics’ leadership, skills, experience, and global footprint. Together, we will improve even more people’s lives with our highly scalable organization.” “We are thrilled to be part of R&Q,” said Maetrics President Steve Cottrell. “Together, we  provide a truly unique consultancy offering to the life science industry. With our combined capabilities, clients know they are working with a leading partner that they can trust to deliver. The healthcare sector is so important to our everyday lives—now more than ever—and both R&Q and Maetrics are dedicated to continually supporting this mission with our effective regulatory and quality solutions.” Fagan, an original founder of R&Q, claims her favorite quote perfectly describes the integration of R&Q and Maetrics: "The whole is greater than the sum of its parts." In alignment with this quote, the teams from both companies have rallied around the integration tagline of being “Stronger Together.” As the companies continue to unite, the combined leadership team aims to continue its mission to enhance the lives of patients, clients, and employees. The two companies have found a very natural fit when working on client programs together. Their similar focuses on culture and aligned vision have already created successes for clients and team members alike.  Together, R&Q and Maetrics offer specialist consultancy services to the medical device, diagnostics, and pharmaceutical industries: Full-service suite of regulatory and quality solutions, including regulatory strategy and submissions, quality systems, safety risk management, and process validation. Expert implementation of complex new regulations, including the EU MDR and IVDR and creation of CERs and PERs, overseen by a former notified body leadership expert on staff. Strong clinical practice supporting EU requirements, providing strategies and turnkey approach to completion of CERs, PERs, and PMS-related deliverables (PSUR, SSCP, PMCF/PMPF plans and reports, PMCF/PMPF surveys), led by the former BSI Global Head of Clinical Compliance. Strategic regulatory compliance consulting to support businesses at the highest levels, usher in effective compliance strategies, support innovation and growth initiatives, and embed a culture of compliance. Regulatory finding response management, providing best practice strategic, tactical, and creative solutions to address NB nonconformity reports, as well as FDA 483 findings, warning letters, and consent decrees, with a highly scalable team for remediation programs. Best-in-class project management by certified project managers who are seasoned device professionals focused on RA/QA. An international footprint to serve client’s needs, including several offices in the United States and a European headquarters based in Nottingham, England. About Regulatory and Quality Solutions LLC Regulatory and Quality Solutions LLC (R&Q) is a leading provider of regulatory and quality consulting and engineering services for medical devices, IVDs, and combination products. Founded by a team of women medical device regulatory experts, R&Q has been providing industry-leading consulting solutions to accelerate the success of life science companies and improve people’s lives since 2008. Its vision is to become a worldwide leader in its market space, achieving significant growth by becoming internationally known for providing exceptional business-balanced leadership that has proven to accelerate the growth of medical device companies and improve people’s lives. For more information, visit RQTeam.com.  About Maetrics LLC Maetrics is an international leader in life sciences quality and regulatory consulting, focused exclusively on compliance strategies for life sciences companies. Since its founding in 1984, the company has provided insights and experience in the biotech, pharmaceutical, diagnostics, and medical device fields, enabling organizations to achieve compliance while remaining competitive and profitable. By delivering actionable, practical, and realistic strategies designed to fit a client’s needs, Maetrics’ team of industry leaders work in collaboration with our clients to implement business, quality, and compliance solutions. With offices based in the U.S., U.K., and Switzerland, Maetrics offers a global reach to respond whenever and wherever a client needs assistance. For more information, visit Maetrics.com. #### Recent Developments in EU Horizontal Legislation By Chris A. Parr - Principal, CRO The EU is constantly publishing new legislation on a variety of topics that have the potential to impact medical devices and IVDs. Often these new laws have complex and lengthy transition periods spanning multiple years. In this blog we will review some of the new and evolving legislation that manufacturers need to be aware of to ensure compliance in the future.  EU Product Safety Legislation   To set the scene one must consider the underlying product safety legislation in the EU which has three components: General Product Safety Regulation (GPSR) – Regulation (EU) 2023/988 EU harmonisation legislation (sectorial) Standards The GPSR outlines the general framework for the safety of non-food consumer products in the EU. It acts as a safety net, covering products, aspects and risks not addressed by harmonisation legislation. It also ensures that all products on the EU market are safe for consumers. Sector-specific EU harmonisation legislation outlines the characteristics and safety requirements necessary for certain products. Products placed on the EU market must comply with this legislation e.g. medical devices, IVDs, personal protective equipment and toys. Standards are technical specifications adopted by a recognised standardisation body and compliance is not compulsory. There are four distinct types of standards1 as follows: International - adopted by an international standardisation body e.g., ISO European - adopted by a European standardisation organisation e.g., CEN or CENELEC Harmonised - adopted on the basis of a request made by the Commission for the application of Union2 harmonisation legislation National - adopted by a national standardisation body e.g. AFNOR Horizontal Legislation?   Horizontal legislation is separate from product safety legislation and applies across multiple sectors or policy areas. It establishes general principles or rules that cut across various domains (e.g. competition law, environmental protection, consumer rights). The General Data Protection Regulation (GDPR) is horizontal because it applies to all sectors handling personal data. Horizontal legislation often provides the overarching principles (e.g. non-discrimination, consumer protection), while harmonisation legislation implements these principles in specific sectors. Harmonisation laws must comply with horizontal legislation. For instance, a harmonised product safety law must still respect horizontal consumer rights laws. New and Emerging Legislation   Sometimes manufacturers overlook the non-medical device and IVD regulations in the naïve belief that they are not required for CE marking or that someone else in their organisation outside of regulatory affairs will take care of it later. However, a single declaration of conformity is required to be drawn up covering all applicable legislation at the time of CE marking. Therefore, a product can only be considered truly compliant when all applicable harmonisation legislation and horizontal legislation has been covered. Notified bodies for medical devices expect manufacturers to comply with relevant EU horizontal and harmonisation legislation, especially when it intersects with the MDR or IVDR. Figure 1: Horizontal legislation in the EU Recent regulations with the potential to impact medical device and IVD manufacturers include: Batteries regulation (EU) 2023/1542 AI regulation (AI Act) (EU) 2024/1689 Packaging/packaging waste regulation (EU) 2025/40 European Health Data Space regulation (EU) 2025/327  In the following sections we will cover each of these regulations in more detail.  Batteries Regulation (EU) 2023/1542 The batteries regulation is a new horizontal regulation that was published in the OJEU in July 2023. Some provisions of the regulation began to apply from the 18th February 2024 (the Date of Application) with the remainder being gradually phased in over a period of 5+ years. Conformity assessment, CE marking and Declaration of Conformity requirements applied from the 18th August 2024. The general date of repeal of the legacy batteries directive 2006/66/EC is the 18th August 2025. The regulation establishes a comprehensive legal framework for the entire life cycle of batteries placed on the EU market. It applies to all types of batteries, including: Portable batteries Light means of transport (LMT) batteries Starting, lighting, and ignition (SLI) batteries Industrial batteries Electric vehicle (EV) batteries All batteries must undergo a conformity assessment, and the requirements vary by battery type and capacity. Medical devices and IVDs typically (although not exclusively) may use or contain portable batteries. The requirements for producers of portable batteries include: Meeting collection targets for waste portable batteries Marking batteries with the symbol for separate collection Marking batteries with the appropriate chemical symbol if they contain > 0.002% Cd, or > 0.004% Pb Complying with extended producer responsibilities (e.g. registration & reporting) Complying with general battery labelling requirements Labelling rechargeable portable batteries with information on the capacity Labelling non-rechargeable batteries with information on the minimum average duration Marking batteries with a QR code Meeting minimum values for the electrochemical performance and durability The regulation also introduces the concept of removability and replaceability and the concept of battery due diligence. Batteries must be designed so they can be taken out of a device without causing damage to the battery or the product. This must be possible using commercially available tools. The requirement applies to portable batteries in products like electronics, medical devices, and construction tools. Once removed, the battery must be replaceable with a new one – either the original or a compatible model. Replacement batteries must be available as spare parts from the device manufacturer for at least 5 years after the product is last placed on the market. Battery due diligence refers to a set of mandatory obligations for large companies to ensure that the raw materials used in batteries are sourced responsibly, with respect for human rights, labour standards, and the environment. Companies must adopt a due diligence policy aligned with international standards and have their due diligence policies and implementation systems independently verified by a notified body. AI Regulation (AI Act) (EU) 2024/1689 The AI regulation (EU) 2024/1689 was published in the OJEU in July 2024. The Date of Application is the 2nd August 2026, and some provisions of the regulation covering unacceptable risk AI systems applied from the 2nd February 2025. The EU AI Act lays down harmonised rules for AI systems that are placed on the market, put into service, or used in the EU. It also prohibits certain AI practices. It is a horizontal regulation and thus applies to AI systems regardless of whether they are covered by other EU legislation or not. Therefore, medical devices and IVDs that utilize artificial intelligence to any degree, may be in scope of the regulation. The regulation introduces four tiers of risk classification for AI systems, with proportionate control measures and monitoring activities. The four categories, examples for each and the type of control are shown in Figure 1. Medical devices and IVDs incorporating an AI system are considered high-risk under the AI Act if they are classified above Class I under the MDR or Class A under the IVDR. For high-risk AI systems, conformity assessment, CE marking and Declaration of Conformity requirements will generally apply from the 2nd August 2027. The requirements of the AI regulation apply to: Providers of AI systems, regardless of whether they are established/located within the Union or in a third country Deployers of AI systems that are established/located within the Union Importers and distributors of AI systems Authorized representatives of providers who are not located within the Union Figure 2 – Categories of AI Systems Medical devices and IVDs classified as AI systems under the AI regulation that are placed on the market before the 2nd August 2027, are exempt from the requirement to have a conformity assessment in accordance with the regulation. Any significant changes made to those devices after the 2nd August 2027, will trigger the need for a conformity assessment. The regulation utilizes the Notified Body model which is not new to the medical device industry. It also introduces the European AI Board, comprised of representatives from the member states, which acts as a co-ordination platform and advisory body to the Commission (a bit like MDCG currently does under the MDR and IVDR). The regulation also creates a European AI Office which will be tasked with supervising the general-purpose AI models. The conformity assessment required by the AI regulation can be combined with that for the MDR or IVDR and performed by the same Notified Body if they are designated under the AI regulation. The QMS requirements of the AI regulation can be combined into the QMS required by the MDR and IVDR. The recently released guidance from the Artificial Intelligence Board (AIB) and the Medical Device Coordination Group (MDCG) (AIB 2025-1 MDCG 2025-6) provides welcome guidance in this area. Packaging/packaging waste regulation (EU) 2025/40 The packaging/packaging waste regulation (EU) 2025/40 was published in the OJEU in January 2025 (abbreviated as “PPWR”). The Date of Application is the 12th August 2026, and the legacy directive 94/62/EC will be repealed from that date. The new regulation is horizontal and applies to all packaging and packaging waste generated from all sources e.g. commercial, household, and industrial. The PPWR is built on the extended producer responsibility scheme and is aligned with the EU’s New Circular Economy Action Plan (CEAP) which has the goal of making all packing reusable or recyclable in an economic way by 2030. The PPWR applies to all medical devices and IVDs. However, given the critical nature of medical devices and IVDs the obligations for manufacturers are significantly reduced compared with those for other sectors. The intent of the PPWR is that packaging should be designed, manufactured and commercialised in such a way as to allow for its re-use as many times as possible or for high-quality recycling, and to minimise its impact on the environment during its entire life cycle and the life cycle of the products for which it was designed. The packaging of medical devices and IVDs is defined as “contact-sensitive packaging” under the PPWR. This exempts medical devices and IVDs from most of the requirements of the PPWR but not all of them. The main requirements affecting medical devices and IVDs are. Packaging minimization Labelling Re-use targets Extended producer responsibilities Manufacturers must carry out a conformity assessment to ensure that packaging placed on the EU market complies with the regulation’s sustainability, recyclability, and labelling requirements. The regulation does not require CE marking on packaging. European Health Data Space regulation (EU) 2025/327 The European Health Data Space (EHDS) regulation was published in the OJEU in March 2025. The Date of Application was the 25th March 2025. The regulation established a common framework for the use and exchange of electronic health data across the EU and is considered harmonisation legislation. The EHDS is designed to support a single market for digital health services and products, fostering interoperability and innovation in electronic health record (EHR) systems. It enhances individuals' access to and control over their personal electronic health data, while also enabling the secure reuse of this data for research, innovation, policy-making, and regulatory activities. Primary and secondary use of electronic health data is established by the regulation. Primary use is to support healthcare delivery by enabling individuals and healthcare professionals to access, control, and share personal electronic health data across borders within the EU. Secondary use refers to the reuse of health data for purposes beyond individual patient care e.g. research, innovation, and policy making. The EHDS requires all electronic health record (EHR) systems to comply with the specifications of the European electronic health record exchange format, ensuring that they are interoperable at EU level. The EHDS will also provide researchers and policymakers with access to specific kinds of anonymized, secure health data, enabling them to tap into the vast potential provided by the EU’s health data to inform scientific research, develop better treatments, and improve patient care. EHR systems are classified as products under the EHDS Regulation and must comply with the essential requirements outlined in Annex II of the regulation. These requirements apply to the entire EHR system, not just individual software modules or harmonized components. Manufacturers of EHR systems are responsible for ensuring CE marking and compliance. The CE marking confirms that the EHR system meets EU safety, performance, and interoperability standards. This includes developers of apps or platforms that allow patients or providers to access, store, or manage electronic health data in the priority categories (e.g. patient summaries, prescriptions, imaging, lab results). Conclusion The EU is continuously introducing new legislation that can affect medical devices and IVDs. These laws often have long transition periods, and manufacturers must stay informed to ensure future compliance. Manufacturers must consider all applicable legislation - not just MDR/IVDR - when declaring conformity. This includes both horizontal and harmonisation laws. In the next blog series, learn more about Medical Devices and Other EU Laws. Related Next Steps If you’re having difficulty navigating the EU regulatory landscape and struggling to comply with horizontal EU regulations, our experts specialise in helping manufacturers develop comprehensive regulatory strategies designed to ensure that medical devices and IVDs comply with all applicable EU legislation. Contact us to discuss how we can support your efforts and stay tuned for more updates related to the European Medical Device landscape in our upcoming blog posts. Regulation (EU) No 1025/2012 on European Standardisation The word "Union" refers specifically to the European Union (EU) as a legal and political entity #### Redefining HFpEF Care: Precision Therapies for an Inclusive Future Executive Summary Tricuspid regurgitation (TR), historically overshadowed by left-sided valvular diseases, is increasingly recognized as a significant contributor to heart failure (HF) symptoms, hospitalizations, and mortality. Despite its prevalence, TR often remains undiagnosed or untreated until advanced stages, exacerbating patient morbidity and diminishing quality of life (QoL). TR arises from diverse mechanisms, broadly categorized into primary TR (stemming from intrinsic structural abnormalities like prolapse or myxomatous degeneration) and secondary TR (caused by functional impairments such as annular dilation, atrial enlargement, or ventricular dysfunction). Adding complexity, cardiac implantable electronic devices (CIEDs) can induce TR by interfering with valve apparatus, causing leaflet tethering or perforation. Advances in therapies, particularly transcatheter tricuspid valve interventions (TTVI), are reshaping TR management. However, leveraging these innovations requires a thorough understanding of the mechanisms, phenotypes, and challenges of TR, which this blog aims to explore, thereby establishing the groundwork for a deeper exploration of TTVI in the subsequent blog. Introduction: A Turning Point in HFpEF Care HFpEF represents a critical unmet need in cardiovascular medicine, affecting a significant and growing portion of the HF population. Despite advances in diagnostics and pharmacologic treatments for heart failure with reduced ejection fraction (HFrEF), progress in HFpEF care has been slow and fragmented, leaving patients with few options beyond symptom management. The financial burden of HFpEF is substantial, with the American Heart Association forecasting the total direct medical costs of HF to increase from $21 billion in 2012 to $53 billion in 2030 due to hospitalizations and management of associated comorbidities. A lack of effective treatments amplifies this economic strain, disproportionately impacting underrepresented and aging populations. The heterogeneity of HFpEF has compounded the challenge. As a syndrome with varying phenotypes, it presents differently across patients, requiring precise approaches tailored to individual hemodynamic and clinical profiles. This complexity underscores the need for innovative, evidence-driven solutions that address the full spectrum of HFpEF. Device-based therapies, such as IASDs, and novel approaches like SNA offer new hope for patients who experience persistent limitations despite optimized medical care. By targeting the pathophysiologic underpinnings of HFpEF including elevated LA pressures and pulmonary congestion, these therapies aim to improve QoL, exercise capacity, and reduce heart failure hospitalizations. However, trials like REDUCE LAP-HF II and RELIEVE-HF have shown that patient selection, phenotypic stratification, and tailored endpoints are critical to success. Lessons learned from these trials provide a foundation for future studies that can refine treatment approaches, identify responder populations, and generate robust data for regulatory and reimbursement pathways. Here we explore the state of HFpEF care, focusing on its clinical complexities, current treatment options, and the promise of device-based innovations. By analyzing successes and challenges in recent trials, RQM+ offers 10 forward-looking recommendations for clinical trial design that emphasize precision medicine, advanced technology integration, and payer-aligned strategies. With a combination of clinical innovation, regulatory expertise, and strategic insight, RQM+ is uniquely positioned to guide medtech innovators in transforming HFpEF care. Together, we can unlock new possibilities for patients, ensuring that therapies are not only effective but also accessible and impactful. This is the moment to redefine what’s possible in HFpEF care, bridging today’s unmet needs with tomorrow’s breakthroughs. Understanding HFpEF: Disease State and Target Patient Population HFpEF is characterized by elevated LA pressure, resulting from impaired left ventricle (LV) filling due to diastolic dysfunction. This leads to pulmonary congestion and systemic symptoms such as exercise intolerance and breathlessness. While HFpEF primarily affects older adults, women, and patients with comorbidities like hypertension and obesity, it remains a heterogeneous syndrome with varying phenotypes, including: Exercise-induced left atrial hypertension (EILAH): Patients experience elevated LA pressure during exertion despite normal resting pressures, often in earlier disease stages. Resting left atrial hypertension (RELAH): Persistent LA pressure elevation, often seen in advanced stages of HFpEF with volume overload. Combined pre- and post-capillary pulmonary hypertension (CpcPH): Associated with right ventricular (RV) dysfunction in late-stage disease​. Understanding these phenotypes provides a roadmap for personalized treatment, enabling therapies to address specific hemodynamic and clinical profiles. Such stratification improves trial efficiency and clinical outcomes, ensuring therapies align with real-world needs. Current Therapies: Benefits and Limitations Pharmacologic Approaches:Unlike HFrEF, HFpEF lacks robust evidence-based pharmacotherapies. Current treatments focus on symptom relief and comorbidity management (e.g., diuretics for volume overload). Emerging options, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, have shown modest benefits but do not fully address the underlying hemodynamic dysfunction​. Interatrial Shunt Devices (IASDs) Mechanism: IASDs decompress the LA by creating a left-to-right shunt, mitigating pulmonary congestion and improving exercise tolerance. Clinical Trial Data: REDUCE LAP-HF II identified phenotypic responders with compliant pulmonary vasculature and exercise-induced LA hypertension, though non-responders diluted overall trial outcomes. RELIEVE-HF highlighted challenges in advanced HFpEF populations with RV dysfunction and pulmonary vascular resistance, where outcomes mirrored nonresponders in REDUCE LAP-HF II​. Implications: The success of IASDs hinges on careful patient selection and a balanced approach to trial inclusion criteria, ensuring alignment with both clinical and payer priorities. Splanchnic Nerve Ablation (SNA) Mechanism: SNA targets the splanchnic vascular bed, redistributing blood volume and reducing LA pressure, particularly during exertion. Clinical Trial Data: The REBALANCE-HF trial revealed a subgroup of HFpEF patients who demonstrated significant improvements in exercise tolerance (6MWD) and quality of life (KCCQ). This aligns with the trial's focus on preload-dependent phenotypes, offering a new dimension in HFpEF management. Implications: SNA provides a viable option for patients unsuited for shunt-based therapies or refractory to GDMT, emphasizing the importance of tailoring interventions to patient-specific hemodynamics. Limitations: Heterogeneous Patient Response: Not all HFpEF patients benefit equally; trials suggest better outcomes in early-stage disease with preserved RV function. Right Heart Overload Risks: Chronic left-to-right shunting risks RV strain over time, necessitating careful patient selection. The Hits and Misses in HFpEF Trials Here are some key items of note from recent clinical trials in HFpEF: Hits: Responder Identification: Trials like REDUCE LAP-HF II effectively identified phenotypes most likely to benefit, paving the way for targeted therapies. Durability of Benefits: Data show stable RV function and sustained QoL improvements in responder groups over 2 to 3 years. Use of Real-World Data and Integration of Wearables in HFpEF Trials: Emerging studies, such as the REALIsM-HF trial, illustrate how wearable biosensors like the AVIVO patient patch and accelerometers are redefining HFpEF clinical trials. These devices enable continuous monitoring of physical activity, hemodynamic changes, and arrhythmias, complementing traditional endpoints such as hospitalizations and mortality. By correlating wearable data with biomarkers and patient-reported outcomes (ePROs), these tools provide a real-world perspective on treatment impact, early signs of deterioration, and daily symptom burden, paving the way for precision-driven HFpEF care. Misses: Broad Inclusion Criteria: Trials including advanced HFpEF patients with significant RV dysfunction and pulmonary hypertension diluted overall effectiveness results due to inadequately powered subgroups. Inconsistent Endpoint Achievement: Multiple trials failed to meet hierarchical composite endpoints, underscoring the need for more refined, clinically relevant metrics. Enhanced Recommendations for Future Clinical Trials 1. Prioritize Phenotype-Specific Enrollment Recommendation: Stratify patients by phenotypes such as EILAH or those with compliant pulmonary vasculature. Include comorbidity-specific subgroups (e.g., obesity, chronic kidney disease). Trial Design Suggestion: Conduct stratified multi-arm trials to compare outcomes across phenotypic groups, enabling tailored insights. Rationale: This ensures trials focus on populations most likely to benefit, increasing statistical power and clinical relevance. 2. Expand Endpoint Selection Recommendation: Think beyond hospitalization rates and mortality, so as to include: Dynamic hemodynamic monitoring during exercise Patient-reported outcomes (e.g., KCCQ) Physical function metrics (e.g., six-minute walk distance) Trial Design Suggestion: Use composite endpoints combining hemodynamic, functional, and ePRO measures. Rationale: This provides a holistic view of therapy impact, ensuring endpoints resonate with stakeholders. 3. Design Adaptive and Combination Trials Recommendation: Implement adaptive designs allowing interim analyses to refine enrollment or endpoints. Test IASDs with pharmacologic agents like SGLT2 inhibitors or endothelin receptor antagonists. Combine SNA with pharmacologic agents like SGLT2 inhibitors for systemic and hemodynamic benefits. Trial Design Suggestion: Multi-arm adaptive trials to evaluate IASDs (or SNA) alone, in combination with GDMT, and with adjunctive pharmacotherapies. Rationale: This recommendation improves trial efficiency, reduces costs, and expands understanding of combination therapy potential. 4. Evaluate Long-Term Safety and Durability Recommendation: Conduct long-term follow-up studies (5-10 years) assessing LA pressure control, RV remodeling, and adverse outcomes like pulmonary vascular disease. Trial Design Suggestion: Include imaging-based assessments and follow-up visits to track device performance over time. Rationale: This builds payer and clinician confidence in device safety and sustained patient benefits. 5. Leverage Digital Health and Remote Monitoring Recommendation: Use remote monitoring tools to collect continuous hemodynamic data and patient activity levels. Trial Design Suggestion: Include remote-adjusted endpoints to dynamically evaluate real-world patient responses. Rationale: Such an approach reduces reliance on in-person visits, enhancing trial scalability and data collection. 6. Address Reimbursement Through Economic Endpoints Recommendation: Capture cost-effectiveness metrics, such as QALYs gained and hospital cost reductions. Trial Design Suggestion: Include subgroup-specific analyses to highlight cost savings in high-burden populations. Rationale: This aligns trial outcomes with payer requirements, ensuring market adoption. 7. Explore Combination Endpoints to Reflect Real-World Complexity Recommendation: Use hierarchical composite endpoints, balancing survival, symptom improvement, and functional capacity. Trial Design Suggestion: Weight outcomes to reflect patient and clinician priorities, such as improved KCCQ scores and reduced hospitalizations. Rationale: This captures the multidimensional impact of therapies, ensuring broader applicability. 8. Incorporate Global and Multicultural Trial Designs Recommendation: Conduct trials in diverse regions, tailoring designs to reflect global healthcare disparities. Trial Design Suggestion: Implement geographically stratified enrollment with region-specific analyses. Rationale: This expands therapy access and generates insights into cultural and systemic variations in HFpEF care. 9. Develop Post-Market Evidence Strategies Recommendation: Use registries and real-world studies to validate trial findings and support regulatory renewals. Trial Design Suggestion: Create longitudinal registries tracking safety, effectiveness, and cost-effectiveness across diverse demographics. Rationale: This recommendation strengthens evidence for long-term value, enhancing payer confidence and market penetration. 10. Integrate AI-Driven Diagnostics and Monitoring Recommendation: Use AI for imaging analysis (echocardiography, MRI) to measure LV function, LA pressure changes, and RV strain. Utilize wearables for real-time monitoring of physical activity and hemodynamics. Trial Design Suggestion: Incorporate dynamic imaging during exercise testing and real-world monitoring through wearables to assess therapy impact. Rationale: Such an approach enhances precision in patient selection and provides granular, standardized data to evaluate device effectiveness. Reimbursement Considerations To secure reimbursement, future trials involving devices in the HFpEF space, must integrate both clinical and economic endpoints, demonstrating: Clinical Value: Trials must highlight hard endpoints (for e.g., reductions in hospitalizations and mortality) and responder subgroup benefits to convince payers of therapeutic effectiveness. Economic Analyses: Include cost-offset data, such as reduced hospitalizations and long-term economic savings through avoided complications, to justify coverage. Real-World Evidence: Post-market studies documenting real-world effectiveness across diverse populations will be critical to gaining payer trust and expanding access. Conclusion: Bridging Innovation and Impact in HFpEF Care The future of HFpEF care lies in therapies that embrace phenotypic diversity, innovative diagnostics, and real-world effectiveness. SNA and IASDs highlight the potential of tailored device-based interventions but underscore the need for precise trial designs. By broadening eligibility criteria (along with powered subgroups), integrating digital health tools, and addressing economic considerations, manufacturers can align regulatory success with payer confidence. At RQM+, we empower medtech innovators to navigate these complexities, delivering solutions that are effective, equitable, and impactful. Together, we can shape a future where HFpEF care redefines standards and expands access to life-changing therapies. The time is now; let’s advance HFpEF care through strategic innovation and collaboration. Contact us here. #### SaMD vs. SiMD: What You Must Know for Accurate Classification Distinguishing between Software as a Medical Device (SaMD) and Software in a Medical Device (SiMD) is fundamental for any MedTech company developing software-driven healthcare solutions. Misclassification can derail a regulatory strategy, delay market entry, and lead to compliance risks. Regulators worldwide recognize three broad categories of software: Standalone software (SaMD): Software that functions as a medical device on its own. Embedded software (SiMD): Software that is integral to or part of a physical medical device. Supporting software: Software used for manufacturing, maintenance, or logistics, not considered a medical device itself. Accurate classification determines which regulatory frameworks apply, the required conformity assessment, and the post-market obligations that follow. Understanding these distinctions early helps align design and documentation with the correct pathway. Notably, the same algorithm can be SaMD or SiMD depending on deployment. For instance, an imaging algorithm hosted on a hospital server may be SaMD, but if embedded within the firmware of an imaging device, it becomes SiMD. Defining SaMD vs. SiMD The International Medical Device Regulators Forum (IMDRF) defines SaMD as “software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device.” This definition, adopted by both the FDA and European Commission, sets the standard for global interpretation. In contrast, Software in a Medical Device (SiMD) refers to software that is essential to the operation of a hardware medical device. Examples include firmware in an insulin pump or the control software of an MRI scanner. It is important to note that SiMD is neither easier nor a lower burden approach. Even though SiMD is not submitted separately, IEC 62304, ISO 14971, cybersecurity, validation, and change control still fully apply within the device technical file. Examples: An AI-driven diagnostic smartphone app that detects skin cancer is SaMD, since the software itself performs the medical function. The software controlling a smart insulin pen is SiMD, because it functions only as part of that physical device. A mobile app controlling or interpreting data from a device may be viewed as part of the device or a standalone medical device. This is a common grey area. Regulatory Implications of SaMD If your software qualifies as SaMD, it must meet full medical device regulatory requirements as a standalone product. Under the EU MDR Rule 11, most diagnostic or therapeutic software is classified as Class IIa, IIb, or III, depending on its clinical impact. Self-certification (Class I) is now rare. SaMD manufacturers must prepare comprehensive Technical Documentation, including: Clinical evaluation reports Risk management (ISO 14971) Cybersecurity and usability validation Software lifecycle documentation (IEC 62304) In the United States, SaMD follows the FDA’s risk-based framework. Moderate-risk products often go through the 510(k) clearance process, while novel or higher-risk products may require De Novo or PMA submissions. The FDA’s Digital Health Center of Excellence provides specific guidance, including on clinical evaluation and AI/ML-based devices. Because SaMD stands alone, the developer bears full responsibility for quality management, validation, and post-market monitoring. Regulators also expect continuous vigilance. Frequent updates and cybersecurity patches must be managed with documented risk controls. Regulatory Implications of SiMD Software that functions as part of a physical medical device (SiMD) is assessed within the overall device evaluation. There is typically no separate regulatory submission for SiMD; its safety and performance are reviewed as components of the complete device system. For example, the embedded software in a pacemaker is evaluated under the device’s Class III submission. In Europe, SiMD does not receive a separate classification under Rule 11; it inherits the classification of the parent device. However, the same software standards apply: IEC 62304, ISO 14971, and software validation are all mandatory within the device’s technical file. Regulators also require manufacturers to manage software changes carefully. A significant firmware update may trigger a new submission (such as an FDA supplement or MDR re-certification). Additionally, software that controls or interfaces with a device, like a mobile app operating a connected insulin pump, may itself be considered part of the device system or an accessory subject to equivalent regulation. Another important note: early regulator or Notified Body (NB) consultation is critical to avoid classification disputes. Getting aligned early can save time and help manufacturers avoid risk. Key Criteria to Differentiate When determining whether your software is SaMD or SiMD, consider these guiding criteria: Intended Use: Does the software itself diagnose, treat, or prevent disease? If so, it’s likely SaMD. Dependency on Hardware: If the software only operates with specific device hardware, it’s likely SiMD. Platform of Operation: SaMD often runs on general-purpose hardware (PCs, smartphones, cloud servers), while SiMD typically resides in dedicated medical hardware. Regulatory References: Review FDA guidance on digital health software and the EU’s MDCG 2019-11 guidance for software qualification and classification. Borderline examples: A wearable sensor and companion app may straddle definitions. If the app interprets sensor data for diagnosis, it’s SaMD; if it merely displays readings, it may be part of the SiMD system. Manufacturers should document the rationale for classification in their regulatory files to support interactions with the FDA or Notified Bodies. Impact on Classification and Compliance Accurate classification directly impacts your regulatory and commercial strategy. Misclassifying a product can have serious consequences: Under-classification risk: Treating a SaMD as a non-medical product or accessory can lead to noncompliance and enforcement actions. Over-classification burden: Treating embedded SiMD as a standalone device can waste time and resources through redundant submissions. By classifying correctly, manufacturers can align development and evidence generation with the right regulatory expectations. SaMD developers must establish independent post-market surveillance (PMS) processes for software performance, while SiMD manufacturers integrate PMS into the broader device vigilance system. RQM+ experts frequently advise that classification begins with a clear intended use statement. Precisely defining what the software does and for whom determines whether it meets the definition of a medical device. This clarity ensures alignment between design, regulatory documentation, and compliance obligations. Conclusion and Best Practices Getting the SaMD vs. SiMD distinction right is essential to regulatory success. Companies should: Review formal definitions from the FDA, IMDRF, and EU MDR early in the design phase. Use official tools such as FDA’s Q-Submission process or EU Notified Body consultations to confirm classification. Follow harmonized standards (ISO 13485, ISO 14971, IEC 62304) regardless of type; both SaMD and SiMD require rigorous quality and risk management. Maintain living documentation that clearly records classification rationale and regulatory assumptions. As software continues to blur boundaries, especially with wearables, cloud analytics, and AI, staying informed on evolving regulatory guidance is vital. Accurate classification ensures appropriate oversight, accelerates approvals, and ultimately protects patient safety. As the FDA emphasizes, software that operates independently (SaMD) versus software integral to hardware (SiMD) differ in scope, but both demand disciplined design and evidence-based validation.If you need expert support navigating SaMD or SiMD classification and compliance, contact us. Our team of MedTech specialists is here to help you get it right from the start. #### Stick or Twist? 2025 Is a Big Year for ISO 13485 “Should I stay or should I go?” asked iconic punk rock band The Clash, and ISO 13485:2016 will be at a similar decision point in 2025 when it undergoes its systematic review. This technical brief aims to Provide some background on the systematic review of ISO 13485:2016 Explore the factors involved in that review Share what members of the MedTech industry can do to get involved ISO 13485’s Position ISO 13485 is a critical part of the regulatory framework for medical devices globally. This status is reflected in its title, “Medical devices — Quality management systems — Requirements for regulatory purposes”, where it is not only a sector-specific (i.e. the medical devices bit) quality management system (QMS) standard, but it is also directed towards the regulatory requirements related to a QMS (i.e. requirements for regulatory purposes and the numerous “applicable regulatory requirements” dotted throughout the normative text). This focus means that conformity to ISO 13485 supports market access across many different countries and regions, and provides customers and other stakeholders with some assurance that the respective organization is adhering to specific requirements and best practices related to their role in the medical device industry. The scope of ISO 13485 applies to all types of medical devices (and I include in vitro diagnostic medical devices and software as a medical device in that, too) and all organizations involved in the lifecycle of a medical device. This broad application and crucial position in the foundations of many medical device regulatory frameworks around the world make the future of ISO 13485 of strategic importance to the majority of the industry. Published in 2016, ISO 13485:2016 is the third edition of ISO 13485. It was given a 3-year review period initially and went through a systematic review in 2020 when it was confirmed (i.e. the published 2016 version remains valid and is not updated to a new edition). The review period was then set at the more traditional 5-year period, and thus ISO 13485:2016 is due for another systematic review in 2025. What is the systematic review? Standards are only worthwhile if they are kept up to date, still valid, being used (globally in the case of ISO standards), and still useful. The systematic review of ISO standards is the periodic mechanism for the national standards organizations to review published standards. In this instance, the national standards organizations will be asked whether ISO 13485:2016 is still valid, whether it needs to be updated or if it should be withdrawn. To do this, the national standards organizations should solicit feedback from their national stakeholders in order to make an informed decision in the systematic review. The Survey As preparation for the systematic review of ISO 13485:2016 in 2025, the ISO technical committee responsible for ISO 13485, ISO TC 210 WG1, opened a public survey for users of ISO 13485:2016 to provide feedback to the working group. The questions in the survey aimed to gather information on how ISO 13485:2016 is used, and perceived, by stakeholders in the medical device industry, and how the standard is valued. The survey ran during late 2023 and closed in January 2024. ISO TC 210/WG 1 published a paper, "ISO 13485-2016 Users survey - White paper on the results", outlining some of the results from that global survey. There were over 1600 responses to the survey, with approximately ⅔ of the respondents coming from organizations identifying themselves as the legal manufacturer. The survey allowed the respondents to provide feedback on ISO 13485:2016 either by selecting predefined choices, or by using free text fields. Some of the key highlights from the survey were: ~90% of respondents were very, or somewhat, satisfied with the content and use of ISO 13485:2016; Respondents indicated that their use of ISO 13485:2016 still enabled them to conform, and align, with other management system standards (e.g. ISO 9001, ISO 14001) as required; The stability of ISO 13485:2016 and its compatibility with global medical device regulations were of greater importance to the respondents than ISO 13485 following the harmonized approach for management system standards. Independent of their answers on how satisfied they were with ISO 13485:2016, survey respondents were also able to provide specific comments on each clause of the standard. Over 600 comments were submitted, which ISO TC 210/WG1 have reviewed to determine whether there is a need for technical changes to ISO 13485:2016. There were many requests for ISO 13485 to be updated to reflect the specific requirements of specific national or regional legislation (e.g. the EU MDR), but these kinds of changes would be out of the scope for an ISO management system standard. There were a lot of requests for more specific requirements for certain technologies (e.g. software as a medical device) or certain organization types (e.g. those with virtual offices), as well as calls for further guidance on how to implement the existing requirements. It was clear from the responses that awareness of the existing guidance on the implementation of ISO 13485:2016 was low (see ISO 13485:2016 - Medical devices - A practical guide), in part due to it not being a typical ISO standard format. ISO TC210/WG1 has recognised that further guidance on specific areas would be beneficial, and it should be in a format that is more visible and accessible for organizations (than the current practical guide). Therefore a New Work Item Proposal (NWIP) is underway, which if/when approved will eventually lead to updated guidance in an ISO standard format (e.g. Technical Specification or a Technical Report).  Key stakeholder considerations One of the factors at play in the systematic review decision, will be a desire to transfer ISO 13485 to the harmonised approach used in other ISO management system standards (see Annex SL and Annex SL Appendix 2 REV 4 of ISO/IEC Directives, Part 1 Procedures for the technical work Consolidated ISO Supplement — Procedures specific to ISO). Moving ISO 13485:2016 to the harmonised approach is achievable. A move to the harmonised approach would leave ISO 13485 closely aligned with the structure and content of other management system standards such as ISO 9001 and ISO 14001, a move that could be beneficial for organisations maintaining conformity to multiple management system standards. It would also make combined certification audits (by a certification body) feasible and/or easier. In order for ISO 13485 to remain valid ‘for regulatory purposes’ (e.g. ensure requirements are clear, specific, and require objective evidence to demonstrate conformity), it is likely that modifications to the standard text (of the Annex SL) would be required; the question is whether that would still be acceptable for all stakeholders? The likely number of modifications to the standard text of Annex SL could also increase the development time of the revised standard. At the time of the last systematic review in 2020, several key stakeholders expressed their concerns about the move towards the harmonised approach and called for time to allow ISO 13485:2016 to bed-in whilst other aspects of the medical device industry were still in a state of change. There was also a concern about maintaining alignment with an approach for which the medical device industry has no direct influence over the frequency of updates (e.g. updates to the ISO harmonised approach would be a trigger to revise ISO 13485 at the next review point). As already mentioned, ISO 13485:2016 holds a special place in the foundations of many medical device regulatory frameworks around the world. For example: EN ISO 13485:2016 / A11:2021 is harmonised for the EU MDR 2017/745 and IVDR 2017/746; ISO 13485:2016 is the basis for the Medical Device Single Audit Program (MDSAP) used by participating members Therapeutic Goods Administration (TGA) of Australia, Brazil’s Agência Nacional de Vigilância Sanitária (ANVISA), Health Canada, Japan’s Ministry of Health, Labour and Welfare (MHLW), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), and the U.S. Food and Drug Administration (FDA); ISO 13485:2016 is to be incorporated by reference by the US FDA in February 2026 as part of the amendments to 21 CFR 820; ISO 13485:2016 is leveraged for many guidance documents published by the Global Harmonization Working Party (GHWP) for use by its many members; EN ISO 13485:2016 is a designated standard in the UK for medical devices, active implantable medical devices and in vitro diagnostic medical devices. There are numerous other national regulatory frameworks that are founded on either the principles or requirements of ISO 13485:2003 and/or ISO 13485:2016. Several of the above (and more) were cited as part of the stakeholder feedback for the 2020 systematic review (e.g. from national committees, IMDRF, trade associations and the MDSAP RAC Chair). The US FDA’s incorporation of ISO 13485:2016 as part of the amendments to 21 CFR 820 is now official (it was still a ‘plan’ back in 2019) and other regulatory authorities may have plans involving ISO 13485 too. For example, we know that the European Union and the UK’s MHRA are both official observers to the MDSAP and Singapore’s Health Sciences Authority (HAS) have just recently been added to that list. The MHRA have openly been discussing the idea of utilising MDSAP certification as part of changes to the UK regulatory framework and amongst the recent calls for the urgent revisions to the EU MDR and IVDR there have been requests from industry for the inclusion of MDSAP within the EU framework. The three possible outcomes of the systematic review are confirm, revise or withdraw. At this stage, given the nature of ISO 13485 as summarized above, it is highly unlikely that there would be a vote to withdraw the standard, so I shall not dwell on that further. It comes down to confirm (i.e. retain with no changes) or revise (i.e. a new work item to review and rewrite ISO 13485:2016). Confirmation would leave the 2016 version untouched for the next five years. That is five more years for regulatory frameworks to align with, or get closer to, the requirements of ISO 13485:2016. This would support the aim of getting closer to global regulatory harmonization desired by the IMDRF and many national competent authorities, including a more robust foundation for the efforts around regulatory recognition and reliance. A potential downside to confirmation is that it would be another five years for ISO 13845:2016 to feel more out of touch with the industry, especially when it comes to technology related challenges as the use of artificial intelligence (AI), including machine learning (ML), in both medical devices and in software used within the quality management systems continues to grow. And if the harmonized approach changes further in that time, that is potentially another degree of separation between ISO 13485:2016 and its alignment with other management system standards, which could make it more challenging for organizations claiming conformity to ISO 13485 and other standards such as ISO 9001 or ISO 14001. Aside from switching to the harmonized approach, is there a need to revise the content of ISO 13485:2016? Perhaps. But whilst individually we all may wish for minor revisions to certain clauses of ISO 13485:2016 or the addition of a new requirement, or even the removal of a particularly troubling requirement, the consequences of a revision do need to be considered. Consequences such as: the time it would take to produce the revised edition, during which further changes in the industry may occur and the harmonized approach may change again, the need for organizations to direct resources to QMS updates, training and transition rather than developing new products and monitoring existing products on the market, the cost and duration of implementation for device manufacturers, service providers and conformity assessment bodies, the impact on regulations that are directly or indirectly linked to ISO 13485:2016, the uncertainty that occurs during transition periods, especially where conformity to ISO 13485 is a customer requirement or is leveraged as part of a regulatory reliance scheme. An important question in the confirm vs. revise decision, is “what is the overall benefit for making the changes if the standard is revised?” Would the improvements outweigh the pain and cost of the (non-exhaustive) consequences mentioned above? That is not for me to answer here, the purpose of this blog is to simply raise awareness of the systematic review and the considerations involved. Why is all of this relevant to you? Let’s start with an assumption, if you are reading this blog then you are involved directly or indirectly in the medical device industry. And if that is the case, then ISO 13485:2016 probably plays an important role in what you do, what your customers do, or what your clients or your suppliers do. Therefore, the future of ISO 13485 will have an impact on you or your organization at some level. Which factors are important for you and your organization? Regardless of whether you participated in the public survey, the systematic review is an opportunity to communicate with your national standards organization, either directly, via members of the relevant national mirror committee for ISO TC 210 or via other stakeholders such as trade associations. Here are some of the ways you can get involved and express your views on whether ISO 13485:2016 should be confirmed or revised: Identify the applicable national mirror committee for ISO TC210/WG 1 (e.g. NA 176-01-02 AA in Germany and CH210/01 in the UK) for your location and start a conversation on the topic. Ensure that those voting in the systematic review of ISO 13485:2016 on your behalf (e.g. your applicable national standards organization) are aware of your preferences and concerns related to the possible outcomes of the review (i.e. confirm/no changes, revise or withdraw). Engage with colleagues within your organization and peers within your networks to make them aware of the systematic review and their opportunity to express their views on the review of ISO 13485:2016. Engage with any trade associations or professional bodies with which you or your organization are affiliated and determine if they are establishing a position on the systematic review of ISO 13845:2016. #### Streamlining AE Reporting in PMCF Studies (FDA Perspective) The FDA Exemptions, Variances, and Alternative Forms of Adverse Event Reporting for Medical Devices program may benefit manufacturers in reducing the burden of medical device reporting (21 CFR Part 803, under 21 CFR 80.309(b) where real world data/evidence is being collected, such as in post-market clinical follow-up (PMCF) studies. Our aim is to encourage participation in this dynamic, collaborative process with the Agency by serving as a liaison on behalf of manufacturers.RQM+ PMCF Studies As a Source of Aggregate Data In the course of developing a PMCF data collection study, our team at RQM+ gathers and analyzes aggregate real world evidence provided from healthcare providers (HCPs) based on patient medical records / charts. We conduct PMCF studies by deploying anonymous questionnaires to HCPs through a GDPR compliant vendor. The most common type of PMCF activity we conduct is a retrospective patient-level medical record / chart review which often involves surveying HCPs in the United States, the European Union, and rest of world. Today, the main regulatory driver for PMCF studies is the collection of safety and performance data for compliance with Medical Device Regulation (EU) 2017/745 (MDR), as well as the FDA 522 Postmarket Surveillance Studies Program. Collecting real world data from HCP data allows us to collect safety and performance data from medical devices on a global scale to provide valuable clinical evidence across markets. Safety Data Generated in PMCF Studies As an input to a PMCF study plan, the manufacturer provides a list of potential AEs associated with the medical device based on labelling, risk management and complaint information. We ask HCPs to review patient charts, typically regarding a specific case or procedure, and report whether any of these AEs were observed, to adjudicate the relationship of the event to the device (possible, probable, or causal), the severity of the AE and the outcome to the patient. The collected PMCF data is used to support the benefit-risk profile of the device as well as identify and monitor any unknown or emergent issues. The PMCF process is only one aspect of a robust risk management, complaint handling, and quality management system. What makes our PMCF studies unique, strategic, and valuable to manufacturers is that we can verify use of a device in real-world clinical practice using patient level real world evidence. Depending on the sample size, it is common for PMCF data to generate dozens of device-related AEs usually ranging from mild (such as redness, tingling) to moderate (headache, pain) with varying degrees of device-relatedness. The AE data is considered in the PMCF Evaluation Report, which feeds into the benefit-risk assessment for the device. This data is processed by the company’s complaint handling system, which will determine if the events identified are reportable to regulatory authorities, as well as trend the complaints to identify emerging risks. At the conclusion of the PMCF study, manufacturers have the cumbersome responsibility  of complying with reporting requirements for the AE data collected even though the data may have been proactively solicited. What is the best way to report 50 possibly device-related cases of headache using anonymized patient data where the only personal information known is the country, age, and sex of the patients? What do regulatory bodies require in the reporting submission? The Exemptions And Variances Process If a sponsor's applications is approved, the Exemptions process simplifies many of these concerns around conducting PMCF studies that collect potential negative feedback that must be triaged and analyzed for reportability. The aim is to reduce the burden of reporting individual AEs by granting an exemption or variance, which permits certain deviations from reporting requirements, when associated with a planned PMCF study on a case-by-case basis. Once an exemption is granted, the Agency will communicate to the manufacturer what, how, and when the collected AE data can be reported in lieu of submitting typically burdensome Medical Device Reports. The advantage to the manufacturer is that this permits abbreviated summary AE reporting. Similarly, the benefit to the FDA is reduced review time while continuing to monitor the safety of medical devices, protect patients, and foster the development and availability of cutting-edge medical tech. To submit an Exemption Request, the manufacturer (sponsor) must request the exemption. This is an area where RQM+ could be authorized to liaise on behalf of the manufacturing sponsor to initiate the request. The Exemption Request is submitted during the early planning stages of the PMCF activity with an established list of proposed AEs, device information, description of the PMCF study, and a proposed timeframe for deployment. The FDA is highly engaged in encouraging participation in the Exemptions and Variances process to support collection of real-world evidence from EHRs including PMCF studies, in addition to registries and medical claims databases. At RQM+, we have been impressed with the transparency and collaborative nature of the team at the Office of Product Evaluation and Quality and their commitment to providing a collaborative, iterative, informal review process. There are no set templates or guidelines, and each Exemption Request will be evaluated individually. The FDA will review requests for exemptions and variances case-by-case and may provide specific requirements when granting an application. The manufacturer can expect the Agency to provide tailored information on what information will be required in an abbreviated Summary Medical Device Report and how quickly this is expected after closure of PMCF data collection. See more information regarding this process at: Exemptions, Variances, and Alternative Forms of Adverse Event Reporting for Medical Devices | FDA. Keep up to date: Follow RQM+ on LinkedIn Subscribe to our blog Subscribe to the RQM+ Device Advice podcast  #### Structured Dialogue: A Key to Efficient Regulatory Compliance in the EU As the regulatory landscape for medical devices and in vitro diagnostics (IVDs) in the European Union becomes more stringent, the need for transparent and efficient communication between manufacturers and notified bodies has never been more critical. The structured dialogue process, introduced through MDCG guidance, promises to enhance this communication, providing manufacturers with an opportunity to engage meaningfully with their notified bodies across the product lifecycle. But what exactly is structured dialogue, and how does it fit into the broader regulatory framework? What is Structured Dialogue? Structured dialogue is a formalized communication framework designed to streamline interactions between manufacturers and notified bodies at all stages of the certification lifecycle. This process encompasses four key stages: Pre-application Application Conformity assessment Post-certification It is not a new concept; however, its formalization provides manufacturers with a clearer path for regulatory interactions, helping to align expectations and reduce ambiguity throughout the product lifecycle. The process offers multiple touchpoints where manufacturers can raise questions and clarify regulatory requirements, ensuring that both parties are aligned on what is expected. This can significantly reduce the time and effort required to gain certification, particularly for newer manufacturers or those developing high-risk or innovative devices. The Role of Notified Bodies Notified bodies are crucial players in the structured dialogue process. They facilitate the dialogue but remain within their regulatory boundaries, offering insights into regulatory expectations without crossing into consultation. This distinction is critical, as notified bodies cannot provide specific guidance on how to achieve conformity but can clarify regulatory requirements and outline potential pathways to compliance. Although interactions and communications between a manufacturer and a corresponding notified body are neither new nor uncommon, different notified bodies, such as BSI, TÜV SÜD, and GMED, have established structured dialogue frameworks tailored to their operations. These frameworks typically involve scheduled meetings where manufacturers can present their questions and receive feedback from the notified body. These dialogues often include discussions on technical, administrative, and regulatory matters, depending on the stage of the conformity assessment. Hear directly from representatives of BSI, TÜV SÜD, and GMED and watch the on-demand presentation (including their frameworks mentioned above) and panel discussion, RQM+ Live! #83 – Structured Dialogue: How to Engage with Notified Bodies. Watch Recording and Download Slides Benefits of Structured Dialogue One of the main advantages of structured dialogue is the opportunity it provides for manufacturers to gain clarity on expectations early in the process. While there appear to be no KPIs to measure the success of such interactions, by engaging in pre-application discussions, manufacturers can ensure their submissions meet the regulatory requirements, potentially reducing the likelihood of non-conformities later in the review process. This is particularly valuable for small and medium-sized enterprises (SMEs) or those new to the EU regulatory system, as it helps them navigate the complexities of compliance more effectively. Moreover, structured dialogue can also be beneficial during post-certification activities, such as periodic safety update reports (PSURs) or change modifications. By maintaining open communication with notified bodies, manufacturers can address these requirements proactively, minimizing delays in market access. Challenges and Limitations of Structured Dialogue Despite its benefits, structured dialogue is not without its challenges. One of the primary concerns is the inability of notified bodies to consult directly with manufacturers. While they can provide valuable feedback on regulatory requirements, they cannot advise on specific device-related decisions. This limitation means that manufacturers must come prepared with a solid understanding of their product and the regulatory landscape. Additionally, the process requires manufacturers to take an active role in documenting the outcomes of these discussions. Meeting minutes and other documentation must be carefully reviewed and agreed upon by both parties, ensuring that all interactions are traceable and transparent. Looking Ahead As the structured dialogue process continues to evolve, it is expected to play an increasingly important role in the EU regulatory framework. While it is currently an optional tool, perhaps, it may become a mandatory step for high-risk devices in the future. The ultimate goal of structured dialogue is to enhance regulatory efficiency, helping to bring innovative medical devices and IVDs to market more quickly without compromising safety or quality. #### Summary of FDA Regulatory Changes for Digital Health Devices in Q3 2022 Digital health devices are no longer new on the scene, but the regulatory landscape continues to evolve. As predicted in our blog post earlier this year, the latest development is new U.S. Food and Drug Administration (FDA) guidance documents for digital health devices that were released in September and October 2022. Keeping track of these types of changes can be challenging, which is why we have created a one-stop shop with a breakdown of devices and relevant resources for easy reference. FDA Guidance Objectives The draft documents for digital health devices had been around for a while, but the FDA decided to revise and finalize many of them and create clearer definitions for devices that fall under the umbrella of digital health, including: SaMD - Software as a medical device SiMD - Software in a medical device MDDS - Medical device data systems MMA - Mobile medical apps CADx - Computer-assisted diagnosis that helps physicians determine diagnosis CADe - Computer-assisted detection that detects areas of interest in a scan CADt - Computer-assisted triage that helps determine where to direct patients CDSS or CDS - Clinician decision support software that helps make informed decisions about diagnoses with a faster brain to process patient data DTx - Digital therapeutics, an umbrella term DDx - Digital diagnostics, similar to CADx, that takes inputs and helps aid in diagnosis The objective behind this effort was to get more information to stakeholders, industry participants and patients about how the FDA intends to regulate and how FDA reviewers should operate in the digital health space. Artificial intelligence (AI) and machine learning (ML) are additional areas where the FDA is trying to provide more insight into how devices that use AI and ML will be regulated and what information to include in pre-market submissions. The FDA Digital Health Policy Navigator The Digital Health Policy Navigator is a tool designed to help you determine the appropriate regulatory path for your digital health device. Each step directs you to the relevant guidance documents you should reference. Start by understanding the definition of “software function.” The FDA defines this as a “distinct purpose of the product,” and products may have multiple functions. Examples include data analysis, storage and transfer. The software function may or may not meet the definition of a device. Regulatory oversight is only required for software that meets the definition of a device and could pose a risk to patient safety if the device fails to function as intended. Once you have determined the software functions, complete all seven steps in the navigator for each of them. Step 1: Is the software function intended for a medical purpose?  Devices that include software that has a medical purpose are subject to FDA oversight. A device qualifies for regulation if the software function is “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease.” All regulatory documentation requirements flow from the intended use, so this first step of identifying the intended use, applicable conditions and patient populations is critical. Step 2: Is the software function intended for administrative support of a health care facility? If your software is intended for administrative support, it is not considered a device. This includes administrative support of a healthcare facility or laboratory and also encompasses software for transferring, storing, converting formats or displaying clinical laboratory test data and results. Step 3: Is the software function intended for maintaining or encouraging a healthy lifestyle? If the software is intended for general support of a healthy lifestyle and is not centered around a specific disease or condition, it is not likely considered a device. Exceptions include if the device aims to reduce risk around a specific chronic disease or condition. Low-risk general wellness products are not subject to FDA regulation. Step 4: Is the software function intended to serve as electronic patient records? Software for digitizing or managing patient records is not considered a device. However, if the software has any function designed to interpret or analyze patient records, it may be considered a device. Step 5: Is the software function intended for transferring, storing, converting formats or displaying data and results? Software for storing and transferring medical imagery and other clinical information may be a device if it affects the parameters of another medical device, generates alerts, monitors patients or analyzes that data. Step 6: Is the software function intended to provide clinical decision support? Clinical decision support (CDS) is a software function that may be a device if it meets certain criteria. It specifically depends on whether the software provides recommendations and whether the provider relies on those recommendations.  Step 7: Does the Device Software Functions and Mobile Medical Applications Guidance apply? If the device provides information intended to help patients manage their health, the FDA may regulate it as a device or exercise enforcement discretion, depending on the risk level of the device. Summary of FDA Guidance Documents for Digital Health Devices If you design or manufacture digital health devices, take a close look at the final guidance documents recently released by FDA. These are the documents reviewers reference when assessing medical devices, so it’s important to understand their content. Clinical Decision Support Software  This document covers CDS software and provides examples of non-device CDS functions that meet all four criteria and those that do not meet one or more of the criteria. The goal of the guidance is to clarify the types of CDS software functions that are excluded from the definition of a device.  The four criteria that must be met are that the device is: Not intended to acquire, process or analyze a medical image or signal.  Intended for the purpose of displaying, analyzing or printing medical information about a patient or other medical information. Intended for the purpose of supporting or providing recommendations to a health care professional about prevention, diagnosis or treatment of a disease or condition. Intended for the purpose of enabling such health care professionals to independently review the basis for such recommendations to make a clinical diagnosis or treatment decision. CAD Devices The agency released two documents related to CAD devices: “Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device Data in Premarket Notification (501(k)) Submissions” “Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device Data - Premarket Notification [501(k)] Submissions” These documents pertain to patient radiology images or patient radiology device data and the FDA’s recommendations regarding 510(k)s for these types of devices. The guidance documents include the product codes that each addresses and how to address the technology in regulatory submissions. Medical Device Data Systems This guidance document, which covers Medical Device Data Systems (MDDS), Medical Image Storage Devices and Medical Image Communications Devices, indicates that these devices are not subject to FDA regulation if the software is solely for electronic transfer, storage, conversion of formats or display of medical device data and results. Mobile Medical Applications The “Policy for Device Software Functions and Mobile Medical Applications” guidance document states that software for mobile platforms will be regulated if it meets the definition of a device and poses a risk to patients if it does not function as intended. The document provides examples of devices that do and do not meet the criteria. Cybersecurity in Medical Devices “Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions” is intended to “provide recommendations to industry regarding cybersecurity device design, labeling and the documentation that FDA recommends be included in premarket submissions for devices with cybersecurity risk.” This builds on the guidance documents from 2014 and 2018, and while the 2014 document is still the “final” guidance, FDA has been asking companies to consider and reference this document during the design process and for pre-market submissions. How RQM+ Helps If you market digital health devices and need more regulatory resources, our team is here to help. Whether we’re providing consulting about FDA strategy and submissions, supplementing your team or handling every aspect of a project from start to finish, we have the expertise to deliver business-balanced solutions. If you’d like to see our team in action, check out the RQM+ Live! episode, “Medical Device Software: Top Deficiencies and Requests for Additional Info from FDA and Notified Bodies.” #### Ten Tips for A Successful Use of Total Product Life Cycle (TPLC) Reports The FDA, as part of the transparency initiative, has developed a Total Product Life Cycle (TPLC) report capability on their website (www.fda.gov). The intention behind this new report is to provide existing data to medical device manufacturers that will enable them to proactively address quality related issues as early as possible. The TPLC database allows users to search by type of device (product code) and provides a report that identifies the related 510(k) clearances for that particular product code, recall reports, and medical device reporting (MDR) information for the product code selected. What does that mean? Ultimately, companies should have quality systems that incorporate TPLC information into all aspects of their system; such as supplier qualification/monitoring, risk management, design controls, corrective and preventive action, and complaint handling. Incorporating this information throughout the entire life cycle of the device will bring devices to market more efficiently and with less issues post-launch. The database can be found at the following link: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHTransparency/ucm199906.htm Here are ten tips for improving quality practices by using the TPLC data: 1. Develop strong Regulatory Strategies using TPLC information to research and verify that the Product Code and Regulation classifications for devices are consistent with industry practice. Ensure sound predicate device selection for 510(k) substantial equivalence demonstration; ensure that the right testing is planned and developed to demonstrate that differences between the new device and the predicate device do not pose any new safety or efficacy concerns by reviewing the 510(k) summaries for the product code. 2. Assess potential issues that may arise and feed them into the design input phase of a new or changing device by using Recall and MDR reports which detail specific issues with product in the field. This information allows users to ensure that all potential safety, efficacy and reliability issues are addressed proactively. 3. Calibrate and strengthen non-filing justification documentation for design changes by using the TPLC report to find information regarding known competitor design changes and premarket application position; i.e., did they submit a new 510(k) for a new release…if not, perhaps a letter to file/non-filing justification was completed. #### The Basics of Polymer Analysis: Techniques & Solutions Given the level to which plastics, rubbers, and other materials have impacted modern life, it is easy to see the importance of in-depth polymer analysis. By exploring critical parameters like molecular weight (MW), structure, morphology, and thermal characteristics, chemists can develop a deep understanding of the polymeric materials under test to improve the performance of polymers and plastics for specific downstream applications. In this blog post, RQM+ Lab Services will outline some of the basic techniques used in advanced polymer analysis. Polymer Analysis and Characterization: Things to Consider Unlike many other quality assurance and control (QA/QC) procedures for raw materials, polymer analysis is an extremely holistic process. Generally, polymeric materials are comprised of numerous monomers bound together via a series of covalent bonds with a ‘backbone’ of interlinked carbon atoms. The number of monomers linked together in a chain can extend into the hundreds of thousands. Compounding this complexity further is the fact that the underlying polymerization reactions used to synthetically generate polymers and plastics are extremely varied, yielding a correspondingly diverse range of materials. Consequently, there are many parameters to consider prior to carrying out polymer characterization. A selection of the key criteria in advanced polymer analysis includes: Absolute/relative MW Additive quantitation Antioxidant analysis Copolymer analysis Crosslink density Percent of filler Pigment concentration Residual monomer concentration Which Techniques are Used in Polymer Analysis? As the field of polymer and plastics characterization is so vast, there are numerous techniques and methods that may be prescribed to gain a deeper understanding of your raw materials or products. Mass spectrometry (MS) is the workhorse solution for many of the demands of polymer QA/QC. With an extensive catalog of derivative techniques, it is difficult to hone in on a single method of MS that suits the needs of the plastics industry best. Briefly: MS is an advanced analytical technique used to identify the chemical composition of samples using characteristic spectral fingerprints and to provide quantitation at the percent to parts per billion (ppb) range. It has become essential in polymer analysis due to its flexibility. MS systems can be coupled with myriad other instruments to facilitate a broad range of tests, thus satisfying the dynamic needs of polymer characterization studies. A few examples include: Desorption mass spectrometry (DMS) Dynamic headspace gas chromatography-mass spectrometry (DHGCMS) Gas chromatography-mass spectrometry (GCMS) Another spectroscopic method commonly relied upon to identify known and unknown compounds is Fourier transform infrared spectroscopy (FTIR). It is one of the first-choice techniques used to identify polymeric materials in terms of a class (polyamide, polyester, etc.). While spectroscopy is truly central to modern polymer analyses, it cannot provide all the necessary insights for a full-spectrum characterization. There is an enormous range of techniques and solutions available to chemists today, ranging from thermal analysis (i.e. thermal gravimetric analysis) to specific crosslink density determination. Polymer Analysis with RQM+ Lab Services RQM+ Lab Services is recognized as one of the foremost experts in the field of polymer analysis. We offer analytical testing services for incoming raw materials, MW determination assistance, and comprehensive product deformulation support. If you would like more information about how we can help you gain a better understanding of your polymeric materials, simply contact a member of the RQM+ Lab Services team today. #### The Courage to Say No: Boston Scientific Does What the CE Mark Didn’t Introduction: A Moment of Reckoning   Boston Scientific’s decision to discontinue global sales of its ACURATE neo2 and ACURATE Prime transcatheter aortic valve replacement (TAVR) systems marks a pivotal moment in medical device regulation. Despite obtaining CE Mark approval in Europe, these devices failed to demonstrate non-inferiority in two rigorous randomized controlled trials (RCT), leading to their withdrawal. This development prompts a critical examination of the European Union's regulatory framework and its reliance on Notified Bodies (NBs) for medical device approvals. When innovation skips evidence and regulation skips rigor, it's simply roulette with lives (not progress). The ACURATE Valve's Trajectory: A Case Study The ACURATE neo2 valve received CE Mark approval in April 2020, facilitating its entry into the European market. However, subsequent clinical trials revealed significant shortcomings. A pivotal study published in The Lancet reported a composite rate of all-cause mortality, stroke, or rehospitalization at one year of 16.2% for the ACURATE neo2, compared to 9.5% for competitor devices. Further analysis identified that approximately 20% of the valves were under-expanded, correlating with increased rates of death and stroke. If hindsight is 20/20, the CE Mark might need glasses because two failed RCTs still cleared customs. European Regulatory Oversight: A System Under Scrutiny The European Union's (EU) Medical Device Regulation (EU-MDR) aims to ensure the safety and effectiveness of medical devices. However, the ACURATE case raises concerns about the effectiveness of the NB model. The CE Mark approval, granted despite the absence of robust RCT data, suggests potential gaps in the evaluation process. Moreover, the NB and expert panels (that have been in place since 2021), together failed to raise a red flag on the RCT data that has been widely discussed for a while now! Clearly, the reliance on NBs, which are for-profit private entities designated by EU member states, may lead to variability in assessment standards and potential conflicts of interest. When your safety net is stitched by a dozen private firms with clipboards, don’t be surprised if patients fall through. Contrasting with the U.S. FDA Approach In contrast, the U.S. Food and Drug Administration (FDA) mandates stringent premarket approval (PMA) processes, requiring comprehensive clinical evidence. The ACURATE valve's failure to meet FDA standards underscores the agency's commitment to rigorous evaluation. While the FDA's approach may be more time-consuming, it prioritizes patient safety and device effectiveness, potentially preventing the market entry of suboptimal devices. It may be slow, but the FDA doesn’t trade due diligence for early access and that’s the price of trust. Boston Scientific's Decision: A Model of Corporate Responsibility Boston Scientific's choice to withdraw the ACURATE valves globally, despite their commercial availability in Europe, exemplifies corporate responsibility. Acknowledging the devices' clinical shortcomings and the increased regulatory requirements, the company opted to cease sales rather than compromise patient safety. This decision reflects a commitment to ethical standards and patient welfare. In a world of spin, BSC chose spine; kudos for walking away before patients had to.  Conclusion: Lessons for Regulatory Reform The ACURATE valve's journey from European approval to global withdrawal highlights the need for regulatory introspection. The EU must evaluate the efficacy of the NB model and consider reforms to enhance the robustness of device assessments. Aligning more closely with FDA standards and requirements could improve patient outcomes and restore confidence in European regulatory processes. Boston Scientific's transparency and decisive action set a commendable precedent, emphasizing that patient safety should remain paramount in medical device regulation. If the CE Mark can greenlight what the FDA red flags, maybe it's time to ask whether Brussels is confusing certification with sanctification. Contact Us Ready to take a more evidence-driven, globally aligned approach to regulatory strategy? Let’s talk. RQM+ helps MedTech innovators make smarter go-to-market decisions, navigate regulatory complexity, and ensure their products reach the right patients safely and successfully. We're here to make your MedTech happen. #### The de novo Pathway: Is It Right for My Device? In December 2021, RQM+ acquired AcKnowledge Regulatory Strategies (AcKnowledge RS), a San Diego-based firm specializing in regulatory affairs consulting for the medical device and IVD industry. The integration of this impressive team enhances the extensive RQM+ network of current and former FDA reviewers, scientists, engineers and regulatory and quality experts, and adds additional expertise with FDA submissions. The author of this post is a member of this team, which has done significant work with novel and/or high-risk devices focusing on pre-submissions, 510(k)s, IDEs, PMAs, De Novos, Breakthrough Designation Requests and Safer Technology Program Requests.  "Should I pursue a de novo classification for my medical device?" "Is the de novo pathway the right regulatory pathway for my medical device submission?" If you're asking these questions, you're not alone. Unsurprisingly, the most common answer I give clients who ask me these question is, “It depends." That answer also happens to be one of the top most annoying responses to hear from a regulatory consultant. So, I typically like to follow it up with, "Tell me more about your device, your competitors, and the current standard of care, and let's figure out if the de novo pathway is right for you!" The best way to approach this decision is probably to understand how and why the de novo classification came to be. Prior to the 1997 Food and Drug Administration Modernization Act (FDAMA), the de novo pathway didn't exist. Until then, devices that received an NSE (not substantially equivalent) determination in response to a premarket notification [510(k)] submission were automatically deemed Class III. Class III devices are those considered high risk, therefore requiring the often lengthier Premarket Approval (PMA) process: this new de novo process was designed to usher through any new device that was both 1) unprecedented (novel), and 2) low to moderate risk (or with risk that was easily mitigated). It excluded devices that had already been put into Class III, but it offered a four step automatic reclassification process for novel devices using a risk-based strategy. The 4-step process consists of: (1) the sponsor submitting a premarket notification [510(k)], (2) FDA making a Not Substantially Equivalent (NSE) decision due to lack of predicate, (3) the sponsor submitting a de novo application, and (4) FDA reviewing the application and making a final decision to approve or deny it. This process was streamlined in 2012 when FDA further modified the FD&C Act under the Food and Drug Administration Safety and Innovation Act (FDASIA) to, in their words, "allow a sponsor to submit a de novo classification request to the FDA for novel low to moderate risk devices without first being required to submit a 510(k)." They added a more efficient, two-step, automatic reclassification process consisting of just the last two steps of the four-step process outlined above. This allows the sponsor to skip the 510(k) and NSE decision. However, the de novo application in both processes should either refer to a previous 510(k) or include all the relevant information recommended for a 510(k) submission. Also keep in mind that the de novo application should sufficiently address the characterization of all health risks of the device, as well as how those risks might be mitigated. FDA will then review the application, and may work with the sponsor to get more information. If FDA grants the decision, the device can be legally marketed and the new classification (and any applicable special controls) will be published in the Federal Register Notice. In short, if you have a novel technology that isn’t considered high risk (or if the risks can be adequately mitigated) you might be able to get on the market without a costly, lengthy PMA. A de novo classification for your device may then pave the way for other companies to use your device as a predicate: you will have helped decide the regulatory requirements for future clearances, and have the “first-to-market” claim with your technology.  One more thing to keep in mind: FDA strongly encourages a Pre-Submission (Pre-Sub) to informally request guidance on a novel device. However, a sponsor should only submit a Pre-Sub for a de novo application after the device design and intended use are established. It's also recommended that the sponsor have adequate information collected regarding the safety and effectiveness of the device. If you can submit an acceptable de novo application where the necessary performance testing is completed, the risks to health have been mitigated, and the special controls have been identified, then FDA aims to have a decision to you within 60 days. When deciding whether the de novo pathway is right for your company, be sure to do your homework and regulatory research to show that your device is de novo eligible. It's never been easier to do so, as in recent years the number of successful submissions has increased, and information about them has become more accessible: For starters, make sure that your device is in fact new, and not already classified, by researching the available FDA databases (510(k), PMA, Product Classification) and prior FDA decisions. Second, check out the FDA de novo classification process guidance document and read the FDA guidance on determining benefit-risk factors.  Additionally, in 2010 FDA began releasing summary documents for devices classified through the de novo process. The table shown below is featured on FDA's Evaluation of Automatic Class III Designation (de novo) Summaries, where you can read up on devices that have made it through this way. CLICK ON IMAGE TO SEE FULL TABLE #### The German DiGA Idea: Revolutionizing Health Care with Digital Health Applications “The world is moving so fast these days that the man who says it can't be done is generally interrupted by someone doing it.” ― Elbert Hubbard In the rapidly evolving landscape of health care, the DiGA (Digital Health Applications) concept stands as a beacon of innovation and transformation. Originating in Germany, DiGA is making validated health care technologies accessible and reimbursable for patients, setting a precedent for global health care practices. The Purpose of DiGA DiGA aims to make health care technologies reimbursable and accessible to patients. This concept was rigorously tested in Germany to ensure that patient-centered digital innovations provide real health care benefits. Following its success in Germany, DiGA has quickly gained traction in other European countries, and now, it is making its way to the US. Dr. Cordula M Stover, Senior Medical Writer at RQM+, shared her insights on this topic at the 12th Annual Outsourcing in Clinical Trials conference in Munich. She highlighted the achievements and challenges of clinical research in the digitizing German landscape and emphasized the critical role of CROs (Contract Research Organizations) in navigating the regulatory complexities. The Digital Context eHealth, the application of information technology to health care, and mHealth, which focuses on empowering patients through mobile technologies, have been promising solutions for managing chronic diseases and standardizing patient support. The COVID-19 pandemic further accelerated the need for digital health solutions like telemedicine consultations, e-consent for trials, and remote health care programs, proving their feasibility and effectiveness. Medical device digital technology leverages existing software to improve disease management, patient adherence, and treatment deployment. These technologies empower patients to take a more active role in their health care, aligning with the principles of self-managed and guideline-compliant care provision. The Transformative Potential of Digital Health Applications The German health care system, known for its “pooled risk,” solidarity-based, universal health care insurance, provided the perfect environment for the DiGA initiative. The vision was to create a legal framework that scientifically validates technology to address specific health care needs, such as bridging regional disparities and improving health literacy. Manufacturers can access a market where their innovations become reimbursable once their added value is demonstrated. The Federal Institute of Medicinal Products and Medical Devices (BfArM) operates a fast-track process, often navigated with the help of CROs, to bring these digital health applications to market. The Role of CROs CROs play a vital role in the DiGA ecosystem, offering regulatory consultation from invention to market listing and post-market surveillance studies. They ensure that digital health applications meet ISO 14155, EU MDR 2017/745, and other regulatory standards. CROs provide the expertise to manage the complexities of clinical investigations and help ensure that DiGAs fulfill all criteria to be effective and safe. Navigating the Regulatory Landscape To be classified as a DiGA, an application must be a CE-marked medical device of risk class I or IIa, whose primary function is based on digital technologies. BfArM assesses the quality of data protection, device interoperability, and accuracy against clinical guidelines, ensuring the device meets stringent regulatory standards within a contracted timeline. Real-World Impact and Expansion Currently, DiGAs are being embraced beyond Germany, with countries like France, Belgium, and Austria laying down legal frameworks to support digital health applications. This expansion demonstrates the universal need for such innovative solutions in health care. Conclusion & Next Steps The DiGA concept exemplifies the power of digital health applications to transform health care delivery by making validated, patient-centered technologies accessible and reimbursable. The journey of DiGA from Germany to a broader European and US market underscores its potential to revolutionize health care globally. For a deeper dive into the DiGA concept and its transformative impact on health care, we invite you to download our comprehensive white paper, "The German DiGA Idea." Gain valuable insights and understand how DiGA can shape the future of health care. Explore the possibilities with DiGA and be part of the health care revolution! #### The Most Common Issues Affecting Biocompatibility Tests While biocompatibility testing is necessary to develop safe MedTech devices, several issues complicate the process. From the initial study setup to deriving accurate conclusions, complications can arise at each testing stage. That’s bad news. Any testing obstacles can delay product launches, escalate costs, and compromise patient safety.  In this article, we explore the most common issues that arise during biocompatibility assessments. We also share tips on overcoming these issues and developing a smoother testing process. Let’s first unpack the risks posed by testing challenges.  Are Your Analytical Evaluation Thresholds Sensitive Enough? Analytical Evaluation Thresholds (AETs) are critical benchmarks in the testing process that determine the lowest concentration of a substance that must be reliably identified and quantified in a sample. When performing tests, technicians need to ensure their methodologies are sensitive enough to meet the required AET. This is difficult. Each substance extracted from a device may respond differently to various analytical methods, making it a complex task to ensure that all potential compounds are detected at the necessary levels. Uncertainty factors are used to manage this variation and ensure it’s appropriately accounted for in the AET. The task of accurately detecting compounds is made even more complex by the increasing stringency of regulatory standards. Laboratories conducting biocompatibility testing must therefore keep pace with the latest standards and invest in advanced analytical techniques capable of meeting these evolving requirements. Failing to meet AETs can result in an underestimation of the risks posed by a medical device, leading to harmful substances going undetected. This endangers patient safety and risks non-compliance with regulatory standards — further delaying product approvals and market entry. So, what can you do about it? The first step involves staying up to date with the latest standards and regulations. You then need to ensure your teams have a deep understanding of analytical chemistry, thorough knowledge of the device materials, and rigorous testing protocols required to perform accurate tests. How Do You Manage the Uncertainty Factor? Materials are complex. They’re so complex that no two material samples are the same. Similarly, human biology is so varied that no two patients will react the same way to materials. For biological tests to have value, they need to manage the inconvenient truth that no two things are alike — and that tests are always subject to a degree of uncertainty.  Failing to account for uncertainty factors can lead to misleading conclusions about a device's safety. It might result in the overestimation of a material's biocompatibility, overlooking potential risks that could appear in clinical settings. Conversely, excessive caution due to uncertainty might lead to unnecessary testing and resource expenditure, delaying the product development process. Exhaustive testing can also introduce additional analytical errors, especially when a large number of uncertainty factors are being managed.  To mitigate the impact of uncertainty factors, testing protocols must be robust and comprehensive, especially as materials may respond differently to different methods. Tests should therefore use a range of scientifically validated methods, which are both broadly applicable to all potential extractables and tailored to the specific characteristics of the device. Tests should consider worst-case scenarios and be informed by the latest testing strategies, scientific knowledge, and regulatory guidelines. To save time and resources, you also need a clear idea of when biocompatibility testing is complete.  How Confident Is Your Compound Identification? Each material contains a multitude of compounds, including potential contaminants, degradation products, and individual chemical components. For technicians, the challenge is to detect these compounds and to accurately identify and understand them within the context of biological safety. The limitations of current analytical technologies and the variability in compound responses add to the challenge. Identifying compounds at the trace level, for instance, demands a high degree of sensitivity and specificity that pushes the boundaries of existing methods. In many cases, there are no analytical methods capable of identifying a particular chemical at the needed concentration levels.  While we may never get the ‘full picture,’ we can overcome the problem of compound identification by introducing confidence levels as an evaluation tool. Confidence levels are a quantifiable measure of certainty assigned to each identification made during the testing. The level of confidence for each identification needs to be backed up by data and sound reasoning. Regulators will carefully examine your confidence levels and analysis when assessing your device.  Confidence levels also serve as a strategic solution to the broader uncertainty factor in biocompatibility testing. By assigning and justifying confidence levels, technicians introduce transparency into the testing process, where uncertainties are acknowledged and managed, rather than ignored or overlooked.  Biocompatibility Testing Best Practices Continuously Adapt to Regulatory ChangesStay abreast of evolving regulatory expectations, standards, and guidelines. Adapt your testing strategies accordingly to ensure compliance and maintain the highest standards of patient safety. Conduct Early and Thorough Material CharacterizationBegin with a comprehensive understanding of the materials used in your device. Early material characterization helps anticipate potential issues and allows for informed decision-making throughout the development process. Consider redesigning your testing process to better evaluate specific materials and always verify supplier-provided materials.  Implement Robust Analytical MethodologiesEnsure that your laboratory is using testing methodologies that are sensitive enough to meet the required Analytical Evaluation Thresholds. This involves using advanced analytical techniques, validating these methods to ensure they are fit for purpose, and introducing appropriate controls to ensure the methods remain robust. Embrace Uncertainty with Confidence LevelsMake sure that your laboratory assigns and justifies confidence levels for each identification made. This enhances the credibility of your findings and helps navigate the inherent uncertainties in biocompatibility testing. Perform Strategic Testing and DocumentationPerform targeted testing based on a thorough understanding of your materials and their biological interactions. Document every step, from test design to result interpretation, with a clear rationale and robust data. Collaborate with Expert PartnersClose any knowledge gaps by engaging with partners who have deep expertise in the field. At RQM+, for instance, we help our MedTech partners navigate the complexities of biocompatibility testing, from material selection to regulatory submissions. How RQM+ Can Help Improve Your Biocompatibility Tests When performing biocompatibility tests, meticulous planning, robust methodologies, and a deep understanding of both materials and the regulatory landscape are essential to success. This is where RQM+ can help. As a full-service CRO, RQM+ provides comprehensive testing, analysis, and validation services to support regulatory compliance. Our expert Lab Services team can help you design and perform biocompatibility tests, or navigate any complexities or challenges impacting your tests. Speak with our experts and ensure your tests achieve and maintain regulatory compliance. Contact our team now to find out how we can support your testing process.  #### The New Human Factors Playbook: Why Your Combo Device Submission is Depending on It By Gee Burke MD PhD, recently former FDA (CDER) There has been a shift in the MedTech space. Digital health and wearable technologies recently have flooded the market with innovative devices for consumer use. The explosion of these products isn't just evolving consumer choices, it's fundamentally reshaping what regulators expect to see in a combination product submission. For today's smart injectors, connected inhalers, and diagnostic wearables, Human Factors Engineering (HFE) is the backbone of the new submission strategy. The FDA's 2023 guidance on combination products makes it clear: Evaluation of a combo submission consisting of device and drug/biologic does not occur individually. It's about the seamless system they create. The Regulatory Alarm: It's the System Priority The core evaluation mandate is simple in theory. A sponsor must apply HFE principles to each component and to how they work together as a unified system. What does this mean for the sponsor? They must proactively identify and analyze unique use-related risks that only exist because of the combination. For example: Conflicting Cues: A user gets one instruction from the phone mobile app and a different one from the device's physical wearable interface. Interface Complexity: An overly complicated phone mobile app menu leads to a dosing error with a Bluetooth connected auto-injector. Connectivity Gaps: A wearable sensor fails to sync data to the phone mobile app correctly, causing a user to miss a critical health alert. Regulatory bodies now expect documented evidence that a sponsor has done their due diligence to completely discover incidence points for these specific system-level failures. This often results in the need for human factors validation studies to be more comprehensive than ever. The Digital Leap: Usability Testing Moving Forward Usability testing has digital interfaces and wearables, where testing protocols must expand to cover: The Hardware-Software Cooperation Boat: Does the user transition from physical device operation to the digital companion app feel instinctive and seamless? Diverse User Profiles: Is there testing accessibility for users of different ages, tech-literacy, and physical abilities? New Patterns of Risk: How will mobile app updates be revised if it causes user confusion? What about misinterpreted data visualizations or Bluetooth pairing failures? The new standard requires simulated-use and actual-use validation in realistic environments. This means testing not just the device, but the entire user journey across all physical and digital touchpoints. The User-Centric Pivot: Designing for Real-World Engagement The best combo devices today are designed with user-centered compatibility under general-use technology in mind. The goal is to minimize errors while maximizing user adherence.  Best practices we're seeing lead to success: Radical Simplicity: Streamlining both physical and digital interfaces to reduce cognitive load by the user. Personalization: Configuring device for custom alerts, font sizes, and comfort settings. Actionable Feedback: Using clear data visualization and positive reinforcement to keep users engaged and informed.  Products like continuous glucose monitors demonstrate this pivot. They combine medical-grade accuracy with the intuitive, daily usability of a consumer device. Key Takeaway As digital and wearable technologies become standard products submitted for regulatory approval, demonstrating safety and efficacy means proving the entire user experience. Integrated HFE is the most critical tool for securing regulatory approval, confirming meaningful user adoption, and achieving better health outcomes. The question isn't if you need a robust HFE strategy, but how quickly you can adapt the medical device product to this new reality. What's the biggest HFE challenge you've faced with a digital or wearable combo device? Head over to our LinkedIn post and let us know in the comments! #### The Road to Remediation: Ensuring Quality, Safety, and Compliance in MedTech Most of us are familiar with the fast-paced world of MedTech and the mounting pressures to maintain product quality, safety, and compliance companies face. With the FDA increasing the number of Class I recalls and the EU MDR/IVDR placing greater responsibilities on the Person Responsible for Regulatory Compliance (PRRC), the consequences of non-compliance can be severe, impacting financial performance, company reputation, regulatory standing, and user/patient safety. Fostering a Culture of Quality To succeed in this environment, MedTech companies must prioritize a Culture of Quality. This means making quality and safety the guiding principles behind every decision and action. While cost-saving measures are important, compromising on quality and compliance can lead to significant long-term repercussions. By instilling a Culture of Quality, companies can make routine what other companies spend months or years correcting. A Culture of Quality enables open communications and alignment on issues without fear of repercussions. It also reinforces continuous improvement and removes the roadblocks for those course corrections that are constant in our industry. A company that truly embraces a Culture of Quality should have fewer regulatory findings, fewer product complaints/product issues, less scrap, and fewer field corrections. That same company should expect to see positive employee morale, a reduction in stressful work environment, increased customer loyalty, which translates into increased revenue and market presence. Implementing Continuous Monitoring Continuous monitoring is essential for ensuring that products and processes are meeting the intended outcomes. This involves: Implementing robust systems to track product quality trends Identifying new and potential risks Taking corrective actions when necessary Management review plays a vital role in this process, allowing Quality Management and senior leadership to assess quality trends and make informed decisions based on data-driven insights. When product issues arise, focused investigations, along with conducting a thorough Health Hazard Evaluation, are crucial to assess the potential risks to users and patients. Every medical device company should have healthy complaint handling, post-market surveillance, CAPA, and Risk Management processes and systems in place to quickly identify issue trends, assess risks, and take action when necessary. If these processes and systems aren’t in place or are not healthy, a company can miss indicators that new issues are manifesting or there are new risks that could affect users and patients.  If you feel like these systems may be lacking, an audit or gap assessment may be needed to identify areas of improvement for peace of mind. Starting with a process audit or system gap assessment may bring to light deficiencies that weren’t obvious on a day-to-day basis. Once the gaps are identified, remediation may be necessary to close those gaps and test updated systems for robustness. Remember, you don’t know what you don’t know. By conducting the audit or gap assessment, you will have data to show your processes and systems are either working or are in need of improvement. Four Steps to Remediation Conduct a comprehensive audit of the Quality Management System (QMS) and a gap assessment of the primary product's technical files. This will provide visibility into the majority of issues that can lead to field action crises. For more information on the importance of audits, read our 8 Strategic Advantages of Outsourcing Audits technical brief. Take swift action to develop a remediation plan, then remediate identified gaps, either through internal resources or by engaging external subject matter experts for an unbiased assessment. Remember to consider how one process (or system) links to another. Changes made in one process may affect another. Develop a strategy to maintain ongoing compliance, keeping products and processes current and continuously updated. This allows companies to maintain a state of inspection readiness at all times. Implement a robust closed-loop risk management system to identify and address issues as they occur, as well as routinely review your risk management files against post-market data. This involves gathering data from multiple sources and regularly reviewing product risk assessments, complaint coding for new risks, and ensuring reportability guidance is current. Partnering with RQM+ for Success At RQM+, we understand the challenges that MedTech companies face firsthand. Our team of experts offers specialized solutions across the full product lifecycle, from concept to commercialization to post-market. By partnering with RQM+, you can accelerate your compliance and market success while minimizing the risk of costly regulatory action. The road to remediation may seem daunting, but by fostering a Culture of Quality, implementing continuous monitoring, and taking proactive steps to address gaps, MedTech companies can ensure the quality, safety, and compliance of their products. Partnering with a trusted service provider like RQM+ can provide the expertise and support needed to succeed in today's challenging regulatory environment. For further insights on how to proactively prevent crises and protect your customers, patients, and reputation, watch our on-demand panel discussion Get Ahead of the Crisis: How Your Quality System Can Prevent Negative Impacts on Customers, Patients, and Reputation. In this session, our experts cover the best strategies for preparing for crisis management, including the importance of change control, post-market surveillance data, clear decision points, internal audits, and fostering a culture of quality. Keep up to date: Follow RQM+ on LinkedIn Subscribe to our blog Subscribe to the RQM+ Device Advice podcast  #### The Working Principles of Dynamic Light Scattering Dynamic light scattering is a fundamental technique in particle measurement and characterization. It is widely used to illuminate the dimensions of particles in samples as well as their biomechanical and chemical characteristics under distinct conditions. Heterogeneous liquid samples are most commonly subjected to dynamic light scattering as the technique relies on the effect of Brownian motion to characterize dispersed particles by their hydrodynamic radii. This principle enables dynamic light scattering tools to measure the thermodynamic stability of complex emulsions by monitoring particle migration phenomena as a function of time. It can also be used to study protein interactions. What is Brownian Motion? Brownian motion is the erratic and apparently random transportation of dispersed particles within a continuous or semi-continuous mobile phase. This phenomenon is determined by a number of complex mechanisms including gravitational settling and the zeta potential of the colloidal system. It can contribute to colloidal instability by causing particle collisions and separations from the mobile phase, but it can also be used to measure and quantify particles in solution. How Does Dynamic Light Scattering Work? Dynamic light scattering characterizes particle size by shining an incident light source, typically a monochromatic laser beam, into a sample. The sample may be an end-product formulation or a number of particles dispersed in a carrier fluid. The narrow laser beam scatters when it collides with nanoparticles within the solution, diffracting through the sample in multiple directions. An output beam is acquired by an optical detector and variations in the intensity of the laser beam are measured as a function of time. This data is used to calculate the size (hydrodynamic radius) of the particles in solution. Chemists can use this information to research the behavior of colloidal systems, providing accurate insights into their thermodynamic stability in real-world storage, transportation, and usage conditions. Dynamic Light Scattering with RQM+ Lab Services RQM+ Lab Services is one of the leading suppliers of analytical chemistry solutions in the US. We are equipped with cutting edge dynamic light scattering tools to assist in the measurement of dispersed particles and emulsions below the 2.5-micron (um) level. Our dynamic light scattering services are suitable for characterizing proteins, polymers, micelles, carbohydrates, nanoparticles, and more with accurate identification of particles down to a single nanometer (nm). If you would like any more information about our dynamic light scattering capabilities, please do not hesitate to contact us directly. For reading on another technique - A Beginner’s Guide to Dynamic Mechanical Analysis #### The Working Principles of Gel Permeation Chromatography Gel permeation chromatography (GPC) is a powerful analytical technique used to separate dissolved molecules by size, based on their elution from a column filled with a porous gel. It can be described as a type of molecular sieving chromatography, where samples are separated into their constituent parts by dissolving the sample in a mobile phase (solvent) and passing it through a porous column packing. The individual components travel at different speeds through the stationary phase based on their ability to enter different pores, causing the sample to separate in a process known as differential partitioning. Size-exclusion chromatography (SEC) is routinely used for chemical analysis of large molecule species (polymers) and also encompasses many biochemical applications. Gel permeation chromatography is the leading method for measuring the molecular weight distributions of complex polymers. This blog post will explore the working principles of gel permeation chromatography in more detail. Outlining Gel Permeation Chromatography To perform gel permeation chromatography, a solvent is first used to dissolve the sample of interest. The fluid is then continuously pumped into an adsorbent bed, typically comprised of porous gel beads packed into a column. Smaller sample molecules spend more time passing through the porous structure of the column and will take longer to pass through the stationary phase. Conversely, a larger sample molecule cannot traverse through comparatively small pores and will pass through the column quickly. This property is reflective of the individual molecules’ hydrodynamic volumes. The eluted mobile phase molecules can be detected using any of the following techniques: Evaporative light scattering (ELSD) Fourier Transform Infrared Spectroscopy (FTIR) Low Angle Light Scattering (LALS) Refractive Index (RI) Right Angle Light Scattering (RALS) Ultraviolet (UV) Viscometry It is possible to analyze an extremely wide range of molecular weights using gel permeation chromatography columns due to the development of a broad range of specially designed porous polymer packings. Conventional chromatography packings are unsuitable for detecting large molecules as they are often retained in the solid porous structure and do not elute from the column. Finely-tuned porous resins enhance the separating capability of the chromatography columns and can be tailored for enhanced resolution in a specific molecular weight range. This provides narrower separation bands for more reliable polymer molecular weight analysis. Gel permeation chromatography is now one of most widely accepted standards for determining the molecular weight of polymer macromolecules. Gel Permeation Chromatography with RQM+ Lab Services RQM+ Lab Services is one of the leading analytical experts in the field of polymer analysis and molecular weight determination. We operate a wide range of gel permeation chromatography systems with state-of-the-art detection capabilities and support almost any combination of mobile phase and stationary phase.If you would like any more information about performing gel permeation chromatography with RQM+ Lab Services, please do not hesitate to contact us. #### Three Critical Aspects of Analytical Testing for Pharmaceuticals Analytical testing is a cornerstone of pharmaceutical development. It is, of course, essential for ensuring the efficacy and safety of drugs released to market. But compliance and process optimization needs go hand-in-hand with product QA/QC. Various test methodologies factor into identity, potency, purity, and quality verification. Each of these enable drug manufacturers to produce compliant, profitable, high-quality drugs. This blog will dig deeply into three critical aspects of pharmaceutical analytical testing. 1. Identifying Particulates and Residue in Pharmaceuticals Importance of Detecting Foreign Particulates and Residue Detecting foreign particulates and residues is essential for maintaining product purity and safety. Contaminants can pose significant risks to patients, potentially causing adverse reactions or compromising the efficacy of the pharmaceutical product. Additionally, contamination can lead to costly product recalls and damage a company’s reputation. Risks Associated with Contamination Particulates and residues can originate from various sources, including manufacturing equipment, packaging materials, and raw ingredients. These contaminants can result in patient harm, product recalls, and regulatory non-compliance. Ensuring that pharmaceutical products are free from such impurities is vital for patient safety and regulatory approval. Analytical Techniques Used for Identification Several analytical techniques – including microscopy, spectroscopy, and chromatography – are employed to identify particulates and residues. These methods provide detailed information about contaminants' size, shape, and composition, enabling manufacturers to pinpoint their sources and implement corrective measures. Regulatory Requirements and Guidelines Regulatory bodies such as the FDA and EMA have stringent particulate and residue testing guidelines. Compliance with these regulations is crucial for market approval and maintaining product quality. At Jordi Labs, an RQM+ company, we ensure that our testing services adhere to these standards, providing our clients with reliable and accurate results. 2. Extractables and Leachables Testing Definition and Relevance Extractables are chemical compounds that can be extracted from pharmaceutical packaging or container closure systems under laboratory conditions. Leachables are compounds that migrate into the drug product under normal storage conditions. Both can compromise product safety and efficacy if not properly managed. Potential Sources and Risks Extractables and leachables can originate from packaging materials, container closure systems, and manufacturing equipment. These substances can cause toxicity, product instability, and drug-container interactions. Therefore, testing for extractables and leachables is essential throughout the product lifecycle, from development to post-market surveillance. Analytical Methods Used We employ various analytical methods for extractables and leachables testing, including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and inductively coupled plasma mass spectrometry (ICP-MS). These techniques allow for the precise identification and quantification of potentially harmful substances. Regulatory Guidelines and Standards Regulatory guidelines such as USP <1663> and ISO 10993 provide frameworks for extractables and leachables testing. These standards ensure that pharmaceutical products are safe for patient use. At Jordi Labs, we follow these guidelines rigorously, helping our clients achieve regulatory compliance and safeguard their products. 3. Particle Size and Shape Analysis Significance in Pharmaceutical Formulations Particle size and shape significantly impact drug dissolution, bioavailability, and stability. For instance, in inhalation and injectable formulations, particle size and shape influence the delivery and effectiveness of the drug. Ensuring consistent and appropriate particle characteristics is crucial for product performance. Techniques Used for Analysis We use techniques such as laser diffraction, dynamic light scattering, and microscopy to analyze particle size and shape. These methods provide comprehensive data on particle distribution and morphology, which are critical for optimizing pharmaceutical formulations. Importance of Method Validation and Data Interpretation Accurate particle size and shape analysis require meticulous method validation and data interpretation. Validating analytical methods ensures that they produce reliable and reproducible results. Interpreting data accurately allows for informed decision-making in product development and quality control. Regulatory Requirements Regulatory requirements for particle size distribution testing include USP <429> and EP 2.9.31. These standards mandate rigorous testing to ensure the consistency and quality of pharmaceutical products. At Jordi Labs, we adhere to these requirements, assuring our clients that their products meet regulatory standards. Looking for Analytical Testing Solutions? Analytical testing is a cornerstone of pharmaceutical quality and safety. By identifying particulates and residues, extractables and leachables testing, and particle size and shape analysis; companies can ensure their products are safe, effective, and compliant with regulatory standards. Partnering with a trusted service provider like Jordi Labs, an RQM+ company can enhance your testing capabilities and help you navigate the complexities of pharmaceutical analysis, ensuring the highest quality and safety standards for your products. Watch the Recording ▶ "Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers" #### Three for the Price of One: The Latest Amendments to the MDR & IVDR Have Arrived Since their proposal in early 2024, the MedTech industry has been awaiting the formal publication of the latest round of amendments to the EU MDR 2017/745 and IVDR 2017/746. The amendments have now been formally published in the form of Regulation 2024/18601. The regulations cover three topics as shown below. MDRIVDRAmendments to the transition timeline for legacy IVDs that gives manufacturers additional time to keep their IVDD legacy devices on the market, provided they meet certain conditions.✔Amendments to the requirements for the roll-out of EUDAMED, to enable the completed modules to be launched for mandatory use without waiting for all six of the EUDAMED modules to be completed. ✔✔A new obligation for manufacturers to notify their competent authority in the event of anticipated interruptions or discontinuations in supply of devices, where the absence of shortage of said devices could put patients at significant risk. ✔✔ Changes to the Transitional Timelines for IVDR (EU) 2017/746 Despite the extension to the transitional timelines in 20222, the commission has identified a risk of shortages for IVDs, especially high-risk devices, which had a transition deadline of 26 May 2025. The amendment pushes the existing transition deadlines out by a further 2.5 years. The exact transition deadline is dependent on the classification of the IVD device. Like the amendments to the MDR transitional arrangements (Regulation 2023/607), these extended timelines for legacy IVDs come with conditions to enable manufacturers to take advantage of the additional time: The device must continue to comply with the IVDD as well as the transitional provisions of IVDR Article 110(3). This includes meeting vigilance and post market surveillance requirements for IVDR. The device must not undergo any significant changes in design or intended purpose. The device must not present an unacceptable risk to the health and safety of the patient, users or other persons, or to other aspects of the protection of public health. The manufacturer must put in place an IVDR compliant quality management system (QMS) no later than 26 May 2025. The manufacturer must have lodged a formal application for IVDR with a notified body and within four months, the application must be covered by a written agreement between the notified body and the manufacturer. Unlike the extended transition under the MDR (Regulation 2023/607), these dates differ for each classification of upclassified product as shown below. For IVDs classed as ‘general’ under the IVDD that have now been upclassified under the IVDR, their new transition dates are as follows: IVDR ClassificationQMS in place according toArt. 10(8)Lodged application for conformity assessment with notified body (NB)Contract in place with NB for conformity assessmentEnd of transition periodClass D26 May 202526 May 202526 Sep 202531 Dec 2027Class C26 May 202526 May 202626 Sep 202631 Dec 2028Class B &Sterile Class A26 May 202526 May 202726 Sep 202731 Dec 2029 List A and List B IVD devices under the IVDD now have an extended grace period up to 31st December 2027. IVD manufacturers with devices on the market under IVDD (self-declared or through notified body) will have additional time to make the transition to IVDR. The new transition deadline and conditions are similar to what is in place for MDR, so notified bodies are expected to leverage the same procedures already in place for the MDR transition. Self-declaration templates3 and NB confirmation letter templates4 have recently been created for the IVDR transition despite the Commission’s Q&A5 stating that the existing MDR templates are acceptable (with edits) for the IVDR transitional period too. The amendment also extended the deadline for the application of Article 5 (5d) where healthcare institutions are required to justify that their specific needs cannot be met by an equivalent device as part of their supporting evidence for in-house manufactured IVDs. This requirement is now applicable from 31 December 2030 rather than 26 May 2028. RQM+ Recommendations: Remember that plans are living documents that should be revisited and updated in light of new information. The amendments to the transitional period for IVDs may give certain products or product families a new lease of life. The introduction of the ‘substitute device’ concept may also reinvigorate plans for legacy devices that are due to be replaced by new design iterations. Don’t delay in ensuring that your QMS complies with the requirements of IVDR 2017/746 Article 10(8). Make sure that you consider the content of Annex ZB of EN ISO 13485:2016 / A11:2021 and all the relevant MDCG guidance documents. Use the templates provided to ensure that you have supporting evidence for the extended validity of your expired, or soon-to-be expired, certificates. Don’t be complacent. As with the extended MDR transition timelines, the extensions for the IVDR transitional arrangements are principally to give the notified bodies sufficient time to process the IVDR applications. Notified bodies have capacity for IVDR transitions and applications now; waiting until closer to the applicable transition deadlines increases the risks for your project. Use the time wisely. On the flip side, you may wish to use the extra time afforded by the extensions to plan for, and collect, additional clinical data either from performance studies or post-market performance follow-up studies. EUDAMED Roll Out The amendment removes the current requirement that EUDAMED cannot become mandatory until all modules are fully functional. Instead, it allows completed modules to be released and their use becomes mandatory before the entire system is operational. This amendment applies to both the MDR and IVDR. The current status and planned/estimated notification date are tabulated below6. EUDAMED ModulesAvailable forvoluntary usePlanned OJEU publication date 6ActorsAVAILABLEJul 2025VigilanceQ4 2024Jan 2026Clinical Investigation & Performance studiesQ3 2026Q2 2027?*Market surveillanceQ4 2024Jul 2025UDI/DeviceAVAILABLEJul 2025NB & CertificateAVAILABLEJul 2025 *Estimated based on [6] and previous output from European Commission This change is being driven largely by the delays to the final EUDAMED module for clinical investigations and performance studies, which is not expected to be complete until Q3 of 2026. Delayed development of this module under the previous MDR and IVDR framework would delay mandatory use of any of the other modules. EUDAMED is key for competent authorities and the Commission for market surveillance and should also result in benefits for manufacturers such as the visibility of post-market data on competitor products in the EU. RQM+ Recommendations: Get ready now. The notification that certain modules are ready could be published in the Official Journal in just 12 months; 6 months after which the use of those modules will be mandatory. Depending on the volume of products in your catalogue, the generation and collation of the data required for entry into EUDAMED could be a very time-consuming task; and one that should not be left until the notification is published in the Official Journal. Interruptions of the Supply Chain & Product Discontinuations Key stakeholders have indicated that during the transitional period for MDR and IVDR, the supply of many medical devices and IVDs has, or will be, stopped (temporarily or permanently). If there are no alternatives on the market, this interruption in supply will have a critical impact on patients and public health. The amendment introduces a new article (Article 10a) to both the IVDR and MDR. This new article lays down an obligation for manufacturers to give prior notice about any interruptions or discontinuations of the supply of certain critical medical devices and IVDs. The notification must be sent to the national competent authority of the member state in which the manufacturer, or their authorized representative, is based. This notification must occur at least six months before the anticipated interruption or discontinuation. The manufacturer must also notify their affected customers (e.g. health institutions, healthcare professionals and relevant economic operators). The competent authority is responsible for informing the other competent authorities also impacted by the interruption or discontinuation. This is a completely new requirement for medical devices and IVD in the EU, although equivalent requirements are already in place in the EU for pharmaceuticals, and for medical devices in specific member states (e.g. France7) and elsewhere (e.g. US8 and Canada9). This new obligation comes into force on 10th January 2025, but there are still a lot of unknowns relating to this somewhat vague obligation for manufacturers. For example: Will there be a specific and legally-binding list of medical devices and IVDs that will be in scope? Will there be standardised risk criteria to ensure consistent decisions on reporting from manufacturers? How will interruptions due to force majeure situations be treated by the competent authorities? Guidance on this new obligation for manufacturers is expected from both the Commission (in the form of a Q&A document) and the MDCG. RQM+ Recommendations: Prepare. If this requirement is completely new to your organization, you need to determine whether the intended purpose of your device, the clinical context in which it is used and the market for the device create a situation where the loss of your device from the market could lead to serious harm etc. Plan. Establish processes that will help you detect anticipated interruptions to the supply chain, assess the risk and make decisions on whether notifications are required. Assess. Just like when communicating Field Safety Notices, the notification of interruptions and discontinuations could be an exhausting exercise. Check that you have adequate contact information for distributors and customers that would need to be notified in the event of interruptions or discontinuations. RQM+ Services to Help Smooth Your IVDR Transition IVDR Planning and Execution: RQM+ delivers business-balanced strategy and tactical execution for transitioning companies of all sizes to the EU In Vitro Diagnostic Regulation (IVDR). See here to learn how our industry insights and collective knowledge contribute to comprehensive compliance strategies and business-balanced solutions. Performance Evaluation Solutions: RQM+ provide a complete and integrated solution for PEPs, PERs, PMS plans, PMPF plans, risk management, and labeling, with regulatory strategy applied throughout the process. This ensures you put your best foot forward for IVDR approval. Learn how RQM+ can add value to your IVDR performance evaluation efforts. Quality System Regulations and Standards: Regulatory requirements for quality management systems are constantly evolving, and it is up to manufacturers to stay abreast of the changes and stay compliant. The RQM+ team can help you implement best practices for keeping products and associated documentation up to date and compliant. Comprehensive Audit Programs: From internal audits to multiyear agreements auditing your entire supply chain, RQM+ has you covered. Learn all of the ways we help with auditing everywhere in the world and in any language. Acquisition Integration for Medical Devices and IVDs: Acquiring a new company or product line can have a positive business impact, but it also comes with regulatory and quality challenges. RQM+ uses a customized, business-balanced approach and proven practices to integrate new acquisitions into your quality systems. More RQM+ Resources at Your Fingertips: Revisit our MDR blog about what to do during the transition: Musical Chairs MDR-Style: Keep dancing even though the music has stopped Catch up with our Live! show on IVDR Class D devices, focusing on Advanced Strategies for Succeeding In a Dynamic Regulatory Environment Watch the recording of our Live! show: Get Ahead of the Crisis: How Your Quality System Can Prevent Negative Impacts on Customers, Patients, and Reputation Follow RQM+ on LinkedIn for all our updates! View our RQM+ Live! panel discussion this topic - MDR and IVDR Amendments: Strategies for Supply Interruption Compliance Don’t Get Caught Off Guard: How to Meet the EU’s 2024 MDR Deadlines References Regulation (EU) 2024/1860 of the European Parliament and of the Council of 13 June 2024 amending Regulations (EU) 2017/745 and (EU) 2017/746 as regards a gradual roll-out of EUDAMED, the obligation to inform in case of interruption or discontinuation of supply, and transitional provisions for certain in vitro diagnostic medical devices | URL Regulation (EU) 2022/112 of the European Parliament and of the Council of 25 January 2022 amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnostic medical devices and the deferred application of conditions for in-house devices | URL MedTech Europe - Manufacturer’s Declaration in relation to Regulation (EU) 2024/1860 | URL Team-NB - Notified Body Confirmation Letter – EU 2024/1860 (v2) | URL EXTENSION OF THE IVDR TRANSITIONAL PERIODS: Q&A on practical aspects related to the implementation of the extended transitional period provided for in the IVDR, as amended by Regulation (EU) 2024/1860 of 13 June 2024 amending Regulations (EU) 2017/745 and (EU) 2017/746 as regards a gradual roll-out of EUDAMED, the obligation to inform in case of interruption or discontinuation of supply, and transitional provisions for certain in vitro diagnostic medical devices | URL  Updated Timeline - Current planning for gradual roll out and modules’ functionality view | URL LOI n° 2023-171 du 9 mars 2023 LOI n° 2023-171 du 9 mars 2023 portant diverses dispositions d'adaptation au droit de l'Union européenne dans les domaines de l'économie, de la santé, du travail, des transports et de l'agriculture | URL Notifying FDA of a Permanent Discontinuance or Interruption in Manufacturing of a Device Under Section 506J of the FD&C Act | URL Medical device shortages: Overview | URL #### Titrimetry: A Brief Overview At RQM+ Lab Services, we pride ourselves on our scope of expertise. We rely on a fully grounded comprehension of long-standing and cutting-edge chemical testing methods. This enables us to deliver results via a limitless range of finely tailored analytical workflows. Our PhD chemists are highly proficient in virtually any analytical technique geared towards elucidating the chemical makeup of various sample types. Among these, is titrimetry. What is Titrimetry? Titrimetry, sometimes referred to as titration, is one of our core competencies at RQM+ Lab Services. We understand its value to small and medium enterprises (SMEs) in a broad market cross-section, who may not have the capacity to bring critical screening processes in-house. The main goal of titrimetry is to quantitatively measure specific analytes of interest, typically an acid or base, within a given substance using a titrant; a reagent that reacts stoichiometrically with the analyte. In a general experiment setup, the titrant is incrementally added to the solution containing the main component of interest and a relative change is measured using a range of indicators. It is possible to monitor changes visually in some instances. Other detection methods include photometry and potentiometry. These can provide a fully quantitative analysis of titration chemistry. The whole purpose of the titrimetry procedure’s staged chemical reaction is to note what proportion of the titrant has reacted with the analyte. This is recorded – usually continuously – and used to quantify analytes. Industrial Applications of Titrimetry Wine Production Quality is essential to the reputation of any wine producer. This ultimately comes down to a range of closely interlinked factors, including chemical content. Titrimetry is routinely deployed by high-end wineries and quality assurers looking to guarantee pre-defined levels of acidity by screening for compounds like sulfur dioxide. Food Processing In the interests of food safety, a base is often added to a batch of waste vegetable oil to manipulate a reaction that results in the acid and alkaline levels of the solution balancing out with the industry-wide accepted PH level of approximately 8.5 being reached. Titrimetry is routinely used to assist with this stage of food processing. Pharmaceuticals Titrimetry is an integral testing measure applied to a whole host of pharmaceutical development, experimentation, and production phases. With an accurate ability to ensure the chemical properties and purity of all products being a major priority, varying methods of titration testing are heavily depended upon to meet the strict standards and regulations of the pharmaceutical industry.Any impure or contaminated chemical composites could prove catastrophic, making titrimetry a trusted technique of any trained researcher. To learn more about how the long list of titration-related methods we offer could benefit and protect your company’s productivity levels, why not get in contact with a member of our team? #### Transhumanism - Science from Fiction: Part I - Bionic Body Parts Advancements in biotechnology have made things of science fiction into reality. Back in the 70’s, bionic body parts were thought to be donned only by the Six Million Dollar Man1 and The Bionic Woman2. Fast forward forty years and bionic body parts are more science than fiction. As LiveScience.com said, “Scientists are getting closer to creating a bionic human, or at least a $6 million one.”3 Bionic Ears If anyone was in need of an ear, it would probably be a tie between Vincent van Gogh, Evander Holyfield, and the unnamed narrator of Edgar Allen Poe’s “The Raven”. A bionic ear is hot off the press of some researchers at Princeton University.4 Using a 3-D printer, researchers at Princeton University built a bionic ear, complete with integrated electronics. This lab-made ear fabricated the two materials, the biological and electronic, together. By using cells and nanoparticles, followed by a culture broth to combine the electronic components to the tissue, the scientists were able to create a bionic ear. The bionic ear is fully functional, replicating the ability of a human ear (attached to its owner!) and even surpassing it. The finished product contains a coiled antenna inside a cartilage structure, with two wires that lead from the ear’s base and around an electronic “cochlea”. Future research will include the incorporation of other materials, like pressure-sensitive electronic sensors. Bionic Eyes Retina display cameras that process electronic signals into information and send it to an implanted electrode have the potential to restore some retinal function in those who have lost retinal function. Argus II Retinal Prosthesis System5, which is currently in FDA Trials, and a developing technology from Harvard research Fellow, Dr. J. Pezaris1, use a camera to record basic visual information. This visual information is then processed into electronic signals and sent to the patient via implanted electrodes on the retina. The Argus II Retinal Prosthesis System is a wired system that contains a small camera on the center point of a pair of glasses, while the developing technology by Dr. Pezaris will be wireless. Bionic bodies, not all exoskeletons are created equal My favorite Spartan, Master Chief6-13, from the Halo video game/book saga, and Marvel Comic’s Iron Man14 may not be the only bionic, powered exoskeleton armor wearing soldiers for much longer. Researchers from the U.S. Army’s Research, Development, and Engineering Command (RDECOM) are currently developing body armor that has striking resemblances to Master Chief’s MJOLNIR armor and Iron man’s Space Armor MK III. Even the armor’s name, Tactical Assault Light Operator Suit, dons a cool acronym – TALOS.15 TALOS armor may not have deflector shields like MJOLNIR, but RDECOM does intend to use nanomaterial to help aid in lighter, stronger body armor. TALOS is likely to contain a liquid nanomaterial, which MIT scientists are developing. This “liquid armor” uses magnetorheological (MR) fluids16 and relies on magnetic fields; the armor is capable of varying its stability and flexibility depending on the magnetic field it is exposed to.17 According to the US Army’s website17, TALOS will have a “physiological subsystem”. Similar to that of Master Chief and Iron Man’s armor, the TALOS subsystem will be in contact with the skin and embedded with sensors to help monitor core body and skin temperature, heart rate, body position, and hydration levels. USSOCOM’s September 2013 announcement of their interest in receiving white papers reaches out to multiple disciplines spanning from government, academia, industry, and even to individuals.18, 19 When it comes to the possibilities of and the potential that TALOS has, the sky is the limit as the armor may eventually be capable of reading the wearer’s cognitive thoughts and surrounding environment, in order to display information on a Heads-Up Display (HUD). Not only would the suit be equipped with a HUD, but it may even assist in the stabilization of a wounded soldier, who is wearing TALOS, by using a “wound-stasis” program.18 A demonstration of TALOS, with the U.S. Special Operations Command (SOCOM), is scheduled on November 19th, 2013 (mark your calendars!).20 While some exoskeletons are made to make you feel superhuman, others are made to make you feel human, again. Two examples are the Ekso™, a bionic suit developed by Ekso Bionics, and Parker Hannifin’s powered exoskeleton device, Indego®.21,22 The Ekso™ bionic suit enables individuals with lower extremity paralysis, extreme weakness, and neurological diseases to stand and walk.21 This is achieved through utilizing the user’s forward lateral weigh shift to initiate a step, with a weight bearing, four point reciprocal gait. The exoskeleton is powered by motors that move the legs and is worn over the clothing. Users are not inhibited by a pre-determined speed of “turtle slow”, either. This device offers three walk modes: step actuation by use of a button activated by a physical therapist (typically during the first few sessions of therapy), user control step actuation via buttons on the crutches or walker, and user enabled actuating through the movement of the hips. There are also different modes of power – full power, adaptive (Ekso adjusts the power to compensate for the amount of power produced by the patient), and fixed power (either leg contributes a fixed amount of power for stabilization). The device also gathers and transmits statistics and device information, when in use, which can be retrieved through Ekso Bionics’ web server.23 The Indego® allows people with paraplegia the opportunity to stand and walk, while giving them freedom from a wheelchair. I recently learned about this developing technology and I was deeply touched by this device’s concept and purpose.22, 24 The Indego® lightweight, weighing in at 27 pounds, can be disassembled/re-assembled, and can even be worn while sitting. The exoskeleton is capable of providing 100% of the power and support necessary to walk on all types of surfaces and can even adjust the amount of robotic assistance to help aid in stability. To add a cherry on top, this device also incorporates functional electrical stimulation (FES) rehabilitation therapy! Learning about this device made me very proud to be a part of the medical device industry and reminded me of my journey to where I am now, why and how I got here, and where I will be. Stay connected! Part II of this four part blog mini-series includes “Not-so-Vulcan ‘Mind-Melds’”! What are your thoughts, comments, and feedback? I want to know! -RSpelich ^_^ References Jahn, M. Six Million Dollar Man. London: Star Book, 1975. Print. Johnson, K. "The Bionic Woman." The Bionic Woman. ABC. 14 Jan. 1976. Television. Koerth-Baker, M. Bionic Humans: Top 10 Technologies. LiveScience. Available at: http://www.livescience.com/12954-bionic-humans-artificial-limbs-technologies.html. Accessed 16 Sept. 2013. Sullivan, J. Printable ’bionic’ ear melds electronics and biology. Posted 8 May 2013. Princeton University. Available at: http://www.princeton.edu/main/news/archive/S36/80/19M40/index.xml?section=topstories. Accessed on 10 Oct 2013. News & Observer. Duke researchers will offer ‘bionic eye’ for the blind. Available at: http://www.newsobserver.com/2013/08/04/3080796/duke-researchers-will-offer-bionic.html. Accessed on 10 Oct. 2013. Halo: Combat Evolved. Bungie Software. Video Game. Released 14 Nov. 2001. Halo 2. Bungie Software. Video game. Released 09 Nov. 2004. Halo 3: Bungie Software. Video game. Released 25 Sept. 2007. Halo Wars. Ensemble Studios. Video game. Released 3 March 2009. Halo 3: ODST. Bungie Software. Video game. Released 22 Sept. 2009. Halo: Reach: Bungie Software. Video game. Released 14 Sept. 2010. Halo: Combat Evolved Anniversary. Bungie Software. Video game. Released 14 Sept. 2010. Halo 4. 343 Industries. Video Game. Released 6 Nov. 2012. Stan L., Lieber, L. Heck, D., and Kirby, J. The Invincible Iron Man. New York: NY: Marvel Comics Group, 1968. Print. Hoarn, S. Defense Media Network. Tachical Assault Light Operator Suit (TALOS) Request Elicits Response From RDECOM, Others. Posted 15 June 2013. Available at: http://www.defensemedianetwork.com/stories/tactical-assault-light-operator-suit-talos-request-elicits-rdecom-response/. Accessed on 10 Oct. 2013. Ocalan, M. Manetorheological fluids for extreme environments: stronger, lighter, hotter. MIT. 2011. MIT. Available at: http://dspace.mit.edu/handle/1721.1/67592. Accessed on 10 Oct. 2013. Teel, R. Army explores futuristic uniform for SOCOM. Posted 28 May 2013. USARMY. Available at: http://www.army.mil/article/104229/. Accessed on 10 Oct. 2013. USSOCOM. USSOCOM Seeks Ideas for Advanced Assault Suit Development. 20 Sept. 2013. Available at: http://www.socom.mil/News/Pages/USSOCOMSeeksIdeasforAdvancedAssaultSuitDevelopment.aspx. Accessed on 10 Oct. 2013. FedBizOpps. Tectical Asault Light Operator Suit (TALOS) Technologies for Use by Special Operations Forces. 04 Sept. 2013. Available at: https://www.fbo.gov/index?s=opportunity&mode=form&id=2d62002ee85aa7bb758d01e0ddbd32c4&tab=core&_cview=0. Accessed on 10 Oct. 2013. Gourley SR. SOCOM Extends TALOS Technology Timeline Vision. Posted on 23 Sept. 2013. Defense Media Network. Available at: http://www.defensemedianetwork.com/stories/socom-extends-talos-technology-timeline-vision/. Accessed on 10 Oct. 2013. Ekso Bionics. Ekso. Available at: http://eksobionics.com/ekso. Accessed on 10 Oct. 2013. Parker Hannifin Corp. Indego. Available at:http://www.parker.com/portal/site/Market-Tech/menuitem.e9f921bc8ae21676de92b210237ad1ca/?vgnextoid=1914d3ae3339a310VgnVCM100000200c1dacRCRD&vgnextfmt=default. Accessed on 10 Oct. 2013. Ekso Bionics. Variable Assist. Available at: http://www.eksobionics.com/ekso/variable_assist. Accessed on 10 Oct. 2013. Parker Hannifin Corp. Indego Downloads. Available at: http://www.parker.com/portal/site/Market-Tech/menuitem.2ac544c4aa325776de92b210237ad1ca/?vgnextoid=4834d3ae3339a310VgnVCM100000200c1dacRCRD&vgnextfmt=default&display=download&software=Video&querypotential=xyz. Accessed on 10 Oct. 2013. Further Reading - Christmas Tree: Artificial or Real #### Tricuspid Brinkmanship: Are We Overhyping the Right-Sided Revolution? The Hype Train Has Left the Station… But Where’s the Track? The tricuspid valve is having a moment; it’s no longer cardiology's wallflower, it's the toast of the town, sparking dreams in cath labs and boardrooms alike. Once an overlooked oddity, it now stars in high-octane studies like TRILUMINATE and TRISCEND II, igniting debates on whether tricuspid repairs (and replacements) are the next big wave or just a tempest in a teapot. But let's not pop the champagne just yet. Are we gearing up for a breakthrough, or setting the stage for a high-stakes fizzle, reminiscent of earlier transcatheter misadventures? The unique challenges of right-sided heart anatomy (and hemodynamics) demand more than a cursory glance. So, before we toast to the "right-sided revolution," we need to ask: Is this genuine progress or just a game of medical Jenga? Join me as we peel back the layers of hype, examining these trials from all angles: industry, patients, regulators, and payers. Let's sift the real from the hype and see if these interventions will deliver on their grand promises, or if they're destined to be engulfed by their own hubris. Advancing tricuspid innovation is a bit like sending a rover to Mars; exciting, expensive, and everyone’s watching to see if it’ll crash. Heart Valve: When It Flunks the Tight-Seal Test Tricuspid Regurgitation (TR), or as I like to call it, "the leaky valve fiasco," is when your heart's tricuspid valve is more about freedom than control, letting blood flow backward when it should be moving forward. Picture this: In Functional TR or the "Heart-strain leak," the heart’s chambers are like overpacked suitcases, stretched from the inside and struggling to zip up tightly, heart failure being the usual culprit. On the flip side, there's Degenerative TR or "Wear-and-tear leak," where the valve is just tired from years of service, weathered down by age, or perhaps an infection, and not sealing like it used to. Figuring out whether your valve is overwhelmed by pressure or just a tired old gatekeeper helps zero in on how to patch things up, or when to call for backup. Industry Ambitions vs. Clinical Realities: Striking a Perilous Balance Surge of EnthusiasmThe tricuspid market is the new El Dorado for device manufacturers, offering vast prospects for those aiming to fix the infamous "leaky valve fiasco." Much like the gold rush days of early TAVR, there’s a fortune to be made for devices designed for patients previously written off. Cautionary TalesYet, history serves up a reality check as icy as a clinical cold room: what sparkles in trial settings often dulls under the intense scrutiny of real-world applications. The diversity of patient populations and the whimsical nature of TR grading can turn controlled environments into wild cards. Today's petite trials, with their cherry-picking finesse, resemble more of a magician’s parlor trick than a steadfast scientific endeavor. We risk swapping rigorous validation for a credibility clearance sale. Bottom Line: Manufacturers are betting big, but the true jackpot lies in backing bold claims with solid, incontrovertible evidence. Without it, they gamble not just with fortunes but with lives, and in the high stakes game of heart health, the final call will always demand hard proof over hype. Tricuspid devices are like teenagers full of potential and bluster, but can they really clean up their act when put to the test? Parsing the Triumphs and Tensions TRILUMINATE: A Masterclass in Smoke and Mirrors? The star of today’s show is TRILUMINATE, featuring 600 volunteers in a spectacle comparing transcatheter edge-to-edge repair (with the TriClip) to standard medical therapy. The headliner (primary endpoint)? A composite endpoint of mortality, surgeries, hospitalizations, and everyone’s favorite subjective measurement i.e., quality of life improvements via KCCQ. Surprise! The only “win” came from subjective patient questionnaires. Death? Surgery? Hospitalizations? Crickets. The results glow brightly, but only if you're measuring the applause meter, not the survival rate.  We didn’t save lives, but hey, patients felt better! Maybe it was the clip… or maybe it was the placebo effect. Who cares? …Win ratio! If feeling better is enough, maybe we should prescribe spa days instead of clips. The TRILUMINATE imaging sub study adds precious little since firstly, all blinding is out of the window as the clip is clearly visible and secondly, it lacks hard outcome benefits.   What’s missing? A placebo act. That's right, no dummy run. This study compared transcatheter edge-to-edge repair with the TriClip system to… checks notes… pills. Yes, pills. Surely, nothing screams “scientific rigor” like pitting a $30K device against prescription pills.  Evaluating an invasive procedure without a placebo control is like judging a magic show based solely on the magician’s charisma rather than his tricks. The outcome dazzles the naive but leaves the skeptics wanting.   A Flicker of Reality: The PASUTA Registry Not all is lost in the realm of observational studies. The PASUTA registry offers a sliver of real-world data with 1,000 patients showing some benefits from the newer gadget on the block (Pascal device).  The registry included consecutive patients, which is a strength, as voluntary registries often exclude unfavorable cases. For results, clinical outcomes remain meaningless without a control arm and complications were underreported (“no major complications” is rather vague). Once again, without a control group, it’s like relying on audience cheers to gauge a film’s Oscar worthiness. It's nice to hear, but where's the critical acclaim? Let’s not forget that registry studies can describe trends but cannot prove effectiveness. Imagine the insights if these 1,000 patients had been randomized with a sham control arm! TRISCEND II: When “Innovation” Means Trading Bleeding for Surveys Then there’s TRISCEND II, which feels like a rerun of a show you didn’t want to watch the first time. If TRILUMINATE was a magic trick, TRISCEND II is the encore where the rabbit gets eaten by the hat. It follows the same script; big promises based on subjective quality-of-life scores, with no significant impacts on the endpoints that actually matter: death and hospital stays. But wait, there’s more: a 3X increase in bleeding and a need for 9X more pacemakers (because who doesn’t love a side of lead extraction?). Remember these involved specialized coronary sinus leads or leadless pacemakers. Talk of residual risks…and costs. If complications were dollars, we’d all be millionaires. Moving on, this rerun focuses solely on quality-of-life data; unsurprising, as it’s the only positive aspect. My critique remains unchanged: Without placebo controls, these trials are scientifically inadequate.  If complications were confetti, this trial would be a parade. Tricuspid "Fixer-Upper": When the Cure is a Cardiac Backstab Here’s the cold truth: Mending a leaky tricuspid valve is like silencing a smoke alarm while the house burns down. Sure, transcatheter gadgets stop the drip but they might also drop a hemodynamic anvil on the right ventricle. That cozy, low-pressure right ventricle (RV) gets sucker-punched by afterload whiplash and it’s not a mere hiccup.  It is a cardiac horror show. We’re not just fixing valves; we’re playing Jenga with anatomy. Yank one wobbly block (regurgitation), and the tower (RV function) collapses. The result? A “cure” that’s less miracle and more “Oops, we turned your heart into a ticking time bomb.” Before slapping “revolutionary” on every catheter-delivered widget, remember: The heart isn’t LEGO. Nuance isn’t optional, it’s the line between hero and “RV Failure: The Director’s Cut.” Science: Nothing But Roadkill on The Highway to Innovation Once a device hits the market and CMS starts writing checks, clinical equipoise doesn’t just vanish, it’s vaporized by the thermonuclear blast of corporate momentum. The moment reimbursement codes drop, rigorous trials go from “ethically essential” to “commercially irrelevant.” Why? …because in today’s healthcare ecosystem, approval isn’t a scientific milestone, it’s a fiscal finish line. Imagine this: You’re a researcher trying to run a sham-controlled trial for a device already plastered on billboards and touted by “key opinion leaders” wearing sponsored lab coats. Good luck recruiting patients who’d willingly risk getting the placebo when Dr. Instagram already told them the device is “revolutionary.” The scientific method? More like the scientific meth-head desperate, erratic, and chasing the next quick high. Take TRILUMINATE and TRISCEND II, poster children for this farce. These trials didn’t just bend the rules; they snapped them over a knee and tossed the pieces into a quality-of-life survey bonfire. Once CMS reimburses these devices, future trials won’t ask, “Does this work?” They’ll ask, “How fast can we upsell?” The tragedy isn’t just lost data, it’s medicine’s Faustian bargain: trading long-term knowledge for short-term revenue. Maybe we’re practicing faith-based billing, where the dogma is written by whoever owns the patent. Sometimes the road to hell isn’t paved with good intentions, it’s reimbursed by CMS. Patients on the Precipice: Hope, Hype, and the Real World A New LifelineFor those grappling with severe TR, often aged, frail, and saddled with other health woes, these devices herald a new dawn. Dodging the severe risks of open surgery is no trivial feat, and early whispers of enhanced life quality are indeed persuasive. Reality CheckThe patient in the clinic seldom mirrors the 'poster child' of clinical trials. Advanced RV dysfunction and complex conditions frequently throw cold water on the grand promises of transcatheter tricuspid valve interventions. Despite the orchestrated perfection of trial settings, the real world is messier, its patients less forgiving. Manufacturers, driven by tales of unmet needs, push for wide indications at the regulatory gate, only to see early successes dwindle when faced with the gritty reality of clinical practice. This mismatch sets the stage for a drama where initial victories fade, payers wrestle with ballooning costs, and ultimately, the entire healthcare system is left holding the bag. The critical need for better trial design, sub-group analysis and comprehensive follow-up has never been clearer, to ensure that the fleeting brilliance of clinical trial success isn’t overshadowed by the long-term challenges that follow. Question to Ponder: Will real-world data reveal that those with significantly dilated right ventricles experience markedly different outcomes from the general trial population? For patients, these new tricuspid devices promise a revolution; let’s hope it’s not merely a flash flood leaving no escape. Raising the Stakes: The Regulator’s Uncompromising Gaze As a former regulator in the EU battlefields, I’ve watched as gatekeepers elevate standards for clinical evidence, particularly when it comes to novel transcatheter cardiovascular devices. Safety and Durability: The unique dynamics of right-sided circulation present formidable hurdles. Early studies, while optimistic, rarely paint the full picture of long-term success. Post-Market Oversight: Armed with stricter regulations like the EU’s MDR and an increased focus on real-world evidence from the FDA, the watchdogs of our industry demand vigilant, ongoing surveillance post-approval. Reality Check: Regulators must remain unswayed by sheer enthusiasm. Approval should hinge on a mosaic of data, from randomized trials where possible, to extensive registries and relentless follow-ups. Regulators walk a tightrope, balancing the thrill of innovation against the gravity of evidence. Their scrutiny is the crucible in which true breakthroughs are forged or forgotten. Payer Calculus: Proving Value Beyond the Hype Payers, be they private insurers or public health custodians, cast a jaundiced eye on expensive new therapies. They demand incontrovertible proof of cost-effectiveness, fewer hospital stays, and genuinely better patient outcomes. Cost-Effectiveness: Do these interventions stand up to economic scrutiny compared to conventional treatments, especially among the heavily burdened patient populations? Value-Based Care: As the landscape of healthcare compensation evolves, manufacturers must prove beyond a shadow of a doubt that tricuspid innovations not only enhance outcomes but do so cost-effectively to secure both reimbursement and broader adoption. Bottom Line: Absent compelling economic evidence, even the most groundbreaking technologies may find themselves on precarious footing. Can we afford to advance without solid proof, or are we gambling with the health system’s solvency? Payers stand as the final gatekeepers, where the rubber meets the road. If the road is paved with uncertain evidence and unverified claims, are we driving the value conversation into a cul-de-sac? Frontiers of Right-Sided Innovation: Bold Visions, Lingering Questions Despite the thick fog of skepticism, the horizon for tricuspid therapy hints at a radical shift. Upcoming innovations may include: Refined Patient Selection: Sharper criteria that distinguish between various grades of TR, severe functional and degenerative TR types. Technological Improvements: State-of-the-art delivery systems, innovative repair techniques, and superior imaging protocols to streamline procedures and minimize complications. Conduction System Concerns: The proximity of right-sided devices to the heart’s electrical system poses risks that demand innovative solutions for potential pacemaker integration or the avoidance of conduction disruptions. Global Policy Alignment: Regulators worldwide are likely to tighten the reins on evidence requirements, compelling companies to elevate their game in trial design and post-market follow-through. As we venture into these uncharted waters, are we navigating with precision, or are we adrift on assumptions? The echo of initial successes should not drown out the urgent calls for thorough, far-reaching studies. Where We Falter: Gaps, Blind Spots, and Unfinished Business Earlier Intervention: Will devices show greater benefits if used earlier in the disease course, rather than waiting until patients are severely compromised? Synergy With Other Therapies: The dynamic between transcatheter tricuspid interventions and concurrent therapies for heart failure or left-sided conditions remains underexplored. Could integrated, multidisciplinary trials shed new light? Expansive Registries: Comprehensive, real-world data pools are crucial. They can illuminate long-term outcomes and patient-reported satisfaction, sharpening clinical guidelines and shaping future reimbursement landscapes. The paths less traveled in tricuspid therapy are akin to dark comedies; everyone tunes in, curious, yet hesitant to be the first to chuckle out loud. Curtain Call: Walking the Tightrope Between Promise and Pitfall As we bring down the house lights on the tricuspid saga, it's clear this isn't just a tale of medical promise, it's a full-blown drama with potential plot twists. Tricuspid therapy has stepped confidently out of the shadows, parading as a beacon of hope for those once relegated to the wings due to frailty. Yet, let’s not mistake the opening act’s dazzle for a grand finale. The rush of initial data, while intoxicating, can be as deceptive as a magician's sleight of hand. As aficionados of true medical innovation, our applause should be reserved, our skepticism sharp. We must demand rigor over razzle-dazzle, ensuring our pursuit of the next big thing in cardiology isn’t just chasing after the wind. After all, in the high stakes game of heart health, it's critical to know whether we're witnessing a genuine revolution or just another enticing encore that promises more than it performs. At RQM+, we’re committed to navigating these turbulent waters, advocating for a balance between groundbreaking advancements and evidence based medicine. If we aim to truly revolutionize tricuspid therapy, our resolve to remain accountable at every juncture will be our guiding star. Get in touch with our team of experts today to learn more about how we can support your devices. Innovation ignites change; steadfast evidence fans the flames. True transformation demands both.  More from this author: Technical brief: MitraClip and the Business of American Healthcare: Innovation, Inefficiency, and the Cost of Care White paper: Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation Technical brief: Bridging Treatment Gaps in Heart Failure with Reduced Ejection Fraction: Advancing Evidence for Device-Based Therapies Technical brief: Beyond Inclusion: Reimagining Equity and Real-World Impact in Heart Failure Trials On-demand panel discussion: Medical Device Cybersecurity: Proven Strategies for Connected Devices and SaMD Hearts in a Bind: Choosing Between Promise and Predictability #### Tricuspid Regurgitation: State-of-the-Art Insights Introduction: The (Not So) Forgotten Tricuspid Valve Tricuspid regurgitation (TR), historically overshadowed by left-sided valvular diseases, is increasingly recognized as a significant contributor to heart failure (HF) symptoms, hospitalizations, and mortality. Despite its prevalence, TR often remains undiagnosed or untreated until advanced stages, exacerbating patient morbidity and diminishing quality of life (QoL). TR arises from diverse mechanisms, broadly categorized into primary TR (stemming from intrinsic structural abnormalities like prolapse or myxomatous degeneration) and secondary TR (caused by functional impairments such as annular dilation, atrial enlargement, or ventricular dysfunction). Adding complexity, cardiac implantable electronic devices (CIEDs) can induce TR by interfering with valve apparatus, causing leaflet tethering or perforation. Advances in therapies, particularly transcatheter tricuspid valve interventions (TTVI), are reshaping TR management. However, leveraging these innovations requires a thorough understanding of the mechanisms, phenotypes, and challenges of TR, which this blog aims to explore, thereby establishing the groundwork for a deeper exploration of TTVI in the subsequent blog. Mechanisms and Challenges in TR: Decoding Complexity Unique Anatomy Challenges The tricuspid valve's anatomy, with its thin leaflets and crescent-shaped right ventricle (RV), poses distinct challenges compared to left-sided valves. The RV depends heavily on longitudinal shortening for contraction, making it more vulnerable to dysfunction in TR. These anatomical features complicate imaging, diagnosis, and therapeutic interventions, particularly for severe TR. Mechanisms of TR Primary TR: Results from structural abnormalities such as leaflet prolapse, carcinoid disease, or myxomatous degeneration. Secondary TR: Driven by annular dilation, atrial fibrillation (AF), or ventricular dysfunction. CIED-Related TR: Arises from mechanical interference by pacemaker or defibrillator leads, causing leaflet damage or misalignment. Advances in Quantifying Severe tR Modern imaging modalities, including 3D echocardiography and computed tomography (CT), allow precise assessments of leaflet tethering, annular dilation, and jet location, aiding in the evaluation and treatment planning of massive or torrential TR. Hemodynamics of TR: Balancing Pressure and Volume TR disrupts RV performance by increasing preload and reducing forward cardiac output, leading to systemic congestion and RV dysfunction. Key tools for assessment include: Pressure-Volume (PV) Loops: These loops provide critical insights into RV function, showing how TR increases stroke volume and stroke work while lowering afterload. However, these compensatory changes can mask underlying RV dysfunction as forward stroke work does not equate to total stroke work, underlining the importance of comprehensive assessment​. RV-Pulmonary Artery (PA) Coupling: Measures the RV’s adaptation to PA loading conditions. High coupling suggests effective RV function, while low coupling indicates dysfunction, often predictive of poor outcomes post-TTVI. Understanding and evaluating these hemodynamic principles is essential for tailoring interventions to TR-related right HF. Advances in TR Imaging: Bridging Diagnostic Gaps As emphasized during the recent discussions at TCT 2024, "there is nothing moderate about moderate TR", reflects the need for better criteria to guide clinical decisions​. RV enlargement, characterized by increases in end-diastolic volume (EDV) and end-systolic volume (ESV), often precedes overt decompensation. Imaging can detect these changes early, providing critical insights into the compensatory mechanisms and eventual failure of the right heart. Therefore, imaging plays a pivotal role in diagnosing and managing TR, offering detailed insights into disease severity and RV function. Echocardiography: 2D vs. 3D Imaging: While 2D transthoracic echocardiography (TTE) remains the practical choice for TR evaluation, 3D imaging significantly improves accuracy in assessing regurgitant volume and leaflet morphology. Key Metrics for RV Function: Indicators like tricuspid annular plane systolic excursion (TAPSE), systolic velocity (S’), and fractional area change (FAC) are standard for evaluating RV function. However, these metrics often fail to detect early or subclinical dysfunction. Early Detection Needs: Declines in TAPSE, FAC, and right ventricular free wall strain (RVFWS) signal subclinical dysfunction and decompensation, underscoring the need for refined thresholds and advanced diagnostic metrics. Cardiac Magnetic Resonance (CMR): Provides superior accuracy in quantifying regurgitant volume and phenotyping TR by its hemodynamic burden. Emerging Modalities: Techniques such as strain imaging and CT are improving early detection and risk stratification. Standardization of imaging criteria and broader adoption of advanced modalities remain critical to improving diagnostic accuracy. Clinical Phenotypes of TR: Diversity in Presentation and Prognosis TR manifests in a spectrum of phenotypes, each with distinct etiologies, clinical manifestations, and implications for management: Low-risk TR: Minimal comorbidities, less severe TR, and preserved RV function. High-risk TR: Severe TR, significant RV enlargement, atrial fibrillation, and comorbidities such as congestive heart failure (CHF). TR with Lung Disease: Driven by pulmonary hypertension secondary to lung conditions like chronic obstructive pulmonary disease (COPD). TR with Coronary Artery Disease (CAD): Linked to ischemic cardiomyopathy and reduced left ventricular ejection fraction. TR with Renal Disease: Marked by chronic kidney disease, often with systemic complications influencing outcomes. Recent studies suggest clustering patients by phenotypes improves risk stratification, treatment optimization and prognoses, highlighting the importance of tailored management strategies and identifying (and stratifying) responders for TTVI. Potential Emerging Phenotype: Chronic Venous Insufficiency (CVI)Although current data is lacking, patients with chronic venous insufficiency (CVI) could represent an important emerging TR phenotype. Limited data may stem from economic or geographic barriers preventing these patients from accessing care early or being included in outcome studies. As innovations targeting venous disease become more widely available, this subgroup warrants attention. Future research and surveillance are essential to better understand their unique characteristics, disease progression, and responses to evolving therapies. Management of Patients with Right Heart Failure: Strategies and Outcomes Pathophysiology and Challenges TR exacerbates right heart failure by increasing right atrial pressure, causing systemic venous congestion, and impairing cardiac output. The interdependence of the left and right ventricles further complicates management, as dysfunction in one chamber impacts the other. Consequently, TR-induced right heart failure presents unique challenges, requiring a mix of medical and interventional therapies: Therapeutic Approaches Medical Management: Diuretics and pulmonary vasodilators alleviate symptoms and improve hemodynamics but do not address underlying structural issues. Interventional Therapies: TTVI, including edge-to-edge repair (TEER) and transcatheter tricuspid valve replacement (TTVR), are increasingly preferred for patients unsuited for surgery. Timing and Selection of Interventions Emerging tools like the TRI-SCORE guide patient selection for TTVI by predicting outcomes. Early intervention is critical to prevent irreversible RV remodeling and improve survival. Future Directions: Research and Clinical Trials for Advancing TR Care TR presents unique challenges and opportunities for innovation. The following recommendations highlight key areas of ongoing and future research, clinical practice, and technology development to improve outcomes and transform TR management. Strengthen Hemodynamic Assessments to Prevent RV Dysfunction Expand RV-PA Coupling Research: Metrics like end-systolic elastance (Ees) and effective arterial elastance (Ea) derived from PV loops reveal changes in systolic and diastolic performance. Refinement of these metrics and RV-PA coupling ratio thresholds can help identify patients at higher risk of poor outcomes following TTVI. Incorporate Molecular Biomarkers: Pair hemodynamic assessments with advanced biomarkers (viz., genes like ADORA2B and GALNT13), to better detect early RV dysfunction and chronic TR progression. Refine Risk Estimation Tools: Enhance predictive models like TRI-SCORE by integrating biomarkers and advanced imaging metrics for improving patient selection for TTVI and tailoring risk-based management strategies. Advance Imaging Modalities and Standardization Leverage Emerging Imaging Trends: Transition from 2D to 3D echocardiography for more accurate volumetric assessments and improved visualization of tricuspid valve geometry. Adopt Molecular Imaging: Use advanced techniques, such as molecular imaging in conjunction with standard imaging modalities like echocardiography or CMR imaging, to explore valvular and myocardial tissue health, refining phenotyping, and patient stratification. Standardize Imaging Protocols: Collaborate with KOLs from high volume centers on guidelines for imaging parameters to improve consistency in diagnosis, staging, and treatment planning. Enhance Phenotyping for Personalized Therapy Refine Patient Selection: Use advanced imaging, biomarkers, and phenotyping tools to identify TR patients most likely to benefit from specific therapies, such as TTVR or TEER. Cluster Patients by Phenotype: Expand the application of phenotypic clustering to optimize tailored management strategies and survival outcomes. Tailor Therapeutic Approaches Based on Disease Mechanisms Address Annular Dilation: Develop hybrid therapies that combine annular reshaping with leaflet repair to address complex cases of dilation-related TR. Manage CIED-Related TR: Conduct targeted studies on lead repositioning and device modifications to reduce interference with valve function. Explore Adjunctive Therapies: Investigate neurohormonal and anti-inflammatory therapies to complement mechanical interventions and address systemic contributors to TR progression. Drive Innovation in Device Development and Durability Evaluate Long-Term Outcomes: Conduct long-term studies on the durability, safety, and hemodynamic performance of transcatheter devices, focusing on hybrid approaches. Foster Device Innovation: Encourage development of advanced materials and designs to enhance TTVR device durability, biocompatibility, and function in challenging anatomies. Promote Rigorous and Comparative Clinical Trials Compare Therapeutic Approaches: Design trials comparing transcatheter and surgical therapies across phenotypes to define optimal treatment pathways. Focus on Patient-Centered Outcomes: Incorporate metrics like QoL, functional status, and exercise capacity to ensure therapies align with patient priorities. Assess Adjunctive Treatments: Evaluate the benefits of combining mechanical therapies with medical management, such as pulmonary vasodilators or neurohormonal modulators. Advance Risk Stratification and Early Intervention Develop Early Detection Tools: Use imaging advancements and biomarkers to identify patients at risk of RV decompensation before structural changes become irreversible. Expand Access to TTVI: Refine criteria for TTVI candidacy to include patients with moderate disease, ensuring interventions occur before advanced RV dysfunction. Focus on Multivalvular and Comorbid Disease Management Integrate Multivalvular Care Pathways: Address TR in the context of multivalvular disease, ensuring comprehensive evaluation and treatment strategies. Personalize Care for Comorbidities: Incorporate tailored approaches for patients with concurrent conditions such as lung disease, CAD, or renal dysfunction. To put it in a nutshell, collaborative efforts and innovative trial designs will bridge knowledge gaps and drive progress in TR management. Conclusion: Shaping the Future of Tricuspid Regurgitation Care TR is no longer an overlooked condition as it has emerged from the shadows as a critical focus in cardiovascular care. Advances in imaging, phenotyping, and interventional therapies are not only transforming how we diagnose and treat TR but also redefining the possibilities for patient outcomes. These innovations are paving the way for a more personalized, effective, and compassionate approach to managing right-sided heart disease. The path forward demands a multifaceted strategy. Precision diagnostics, including enhanced imaging and molecular biomarkers, are essential for understanding the diverse phenotypes of TR and tailoring treatments accordingly. Refined risk stratification tools like TRI-SCORE and novel technologies, such as 3D echocardiography/CMR, offer clinicians the means to intervene earlier and with greater confidence. Meanwhile, collaborative research efforts and rigorously designed clinical trials are key to optimizing therapeutic pathways, improving device durability, and exploring complementary medical therapies. By integrating these advances into a cohesive, patient-centered model, the care of TR can be transformed from reactive to proactive. This evolution promises not just better survival rates and functional outcomes but also a marked improvement in QoL for patients. The future of TR care lies in this holistic, collaborative approach, where cutting-edge science meets compassionate clinical practice to redefine the standard of care for right-sided heart disease. Key Takeaways: TR is increasingly recognized as a critical contributor to heart failure and mortality, requiring early detection and management. Advanced imaging modalities like 3D echocardiography and CMR are revolutionizing diagnosis and treatment planning. Innovative therapies such as TTVI offer promising outcomes, especially for patients unsuitable for surgery. Personalized strategies, including phenotyping and risk stratification tools like TRI-SCORE, are essential for optimal care. Collaborative research and device development are paving the way for improved patient outcomes and quality of life. #### Typical Molecular Weights of Common Polymers No two polymers are the same. They exhibit different properties depending on key characteristics, such as their molecular weight. Polymer molecular weight (MW) describes the molar mass distribution of a polymer chain, which determines the weight of the macromolecule itself. This can be a difficult subject to unravel, given the sheer diversity of polymeric structures at the molecular level. In fact, it is nigh on impossible to achieve consistent molecular weights within polymer species, therefore the distribution of molecular weight values is assessed via a series of numeric averages. This blog post will explore the typical molecular weights of some common polymers to put the theory into context: Polyethylene Terephthalate (PET) Polyethylene terephthalate (PET) is a pervasive thermoplastic polymer resin with a typical molecular weight of between 8,000 – 31,000. It is used to fabricate an array of commercial and industrial products, including windows, tire cord filaments, and plastic bottles for carbonated drinks. Over 60% of the world’s PET is used to produce synthetic fibres for apparel and industrial purposes. High Density Polyethylene (HDPE) High Density Polyethylene (HDPE) is a lightweight, high-strength engineering polymer. It typically displays a molecular weight in the region of 100,000 – 250,000 and is renowned for its exceptional strength-to-density ratios. HDPE is routinely used to fabricate plastic bags and bottles, toys, and pipe systems. The primary benefit of HDPE is its resistance to an extensive range of solvents and corrosives, resulting in low molecular weight degradation in the presence of harmful substances. Polyethylene can also be found in high and ultrahigh MW versions with molecular weights in the millions of Daltons. Polycarbonate (PC) Polycarbonate (PC) is a thermoplastic polymer designed to exhibit high toughness and good formability to offer excellent functionalities for both commercial and industrial uses. As such, it features one of the broadest polymer molecular weight ranges observed with typical values measuring between 50,000 – 300,000. This durable material is used to manufacture tough electronic components, and structural components for transit applications. The processability of PC is largely dependent upon its molar distribution, with lower mass grades exhibiting superior degrees of formability over higher grades. However, this is accompanied by a proportional drop in the polymer’s strength values. Polyamide Polyamide, or Nylon 6, is a lightweight polymer chain comprising multiple amide bonds. They display comparatively low molecular weights of 10,000 – 50,000 and are broadly used to manufacture non-woven fabrics and packaging materials. It is most commonly used in the automotive sector for application as interior textiles. Polyurethane (PU) Polyurethane (PU) chains exhibit similar molecular weight profiles to polycarbonates, ranging from 50,000 – 300,000. However, they are synthesized using urethanes as opposed to carbonate elements for improved malleability. Despite their similar molecular weight ranges, PU chains are more commonly used to fabricate flexible or insulating components such as foam sponges and textiles. Polystyrene (PS) Among the most instantly recognisable inorganic polymers, polystyrene (PS) is one of the most broadly-used packaging mediums in the world. It displays a wide molecular weight range of 100,000 – 400,000 and is routinely used to fabricate car parts, tissue culture trays, and packaging for a limitless range of commodities. Molecular Weight Analysis with RQM+ Lab Services RQM+ Lab Services is an expert in the field of polymer molecular weight analysis. We operate one of the country’s leading gel permeation chromatography (GPC) facilities for determining the molecular weight of polymer products with rapid turnarounds. If you would like any more information about performing molecular weight analysis with RQM+ Lab Services, please do not hesitate to contact us today. #### Unbiased Outcomes: The Challenges of Equity in MedTech Equity in medical devices is a relatively hot topic, especially for regulators. The World Health Organization (WHO) describes health equity as follows [1]: Equity is the absence of unfair, avoidable or remediable differences among groups of people, whether those groups are defined socially, economically, demographically, or geographically or by other dimensions of inequality (e.g. sex, gender, ethnicity, disability, or sexual orientation). Health is a fundamental human right. Health equity is achieved when everyone can attain their full potential for health and well-being. In this technical brief – published leading up to our 8 August 2024 presentation and panel discussion with the FDA (learn more and register here) – we will discuss some of the key issues, where they occur during the medical device lifecycle, and some recommendations on how to prevent them or adjust for them. What is certain: For a six-letter word equity can be very complicated. Introduction Fairness. Equality. Equity. Bias. These are words that are being used more frequently in conversations and literature within the MedTech industry. In 2023, the International Medical Device Regulators Forum (IMDRF) published a draft of their Guiding Principles to Support Medical Device Health Equity [2]. In early 2024, an independent review panel in the UK reported their findings and recommendations in relation to equity in medical devices [3], swiftly followed by a response (to the panel’s report) from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) [5]. Whilst over in the US, the FDA have been working on various initiatives to enhance health equity in the US [5-8] and to improve diversity in clinical investigations (or studies or trials, if you’d prefer) [9-11] and the collection of race and ethnicity data in adverse event reports [12-14]. What are we actually talking about when we say ‘equity in medical devices’? I think we can all agree on this: Everyone is different. We all have different needs, situations, preferences, abilities, resources, and outlooks on life. Therefore, we cannot give everyone the same and expect to get the same outcomes. Equality, and ‘being fair,' is commonly seen as giving everyone the same. I am sure that many of you reading this will have seen the widely used image of the people standing on the same size of box to try and look over a fence, where the smallest person in the group still cannot see over the fence. Equity, however, is giving everybody the resources (goods, information, technology etc.) needed to achieve the same outcome. So, in the image, this is shown by each person getting a box size that is inversely proportional to their height, so that all of them can see over the fence. This can be summarized as ‘equal outcome rather than equal provision’. Interaction Institute for Social Change | Artist: Angus Maguire In the IMDRF’s final document [2], they call out six key factors that contribute to differences in populations (for regulators to consider). These six factors are: age, sex, gender, race, ethnicity, and socio-economic status. These factors give us a rough outline of what we are aiming for: ‘equal outcomes regardless of sex, gender, gender identity, race, ethnicity and socio-economic status’. What gets in the way of achieving this? Quite a lot of things, actually. In their report, the UK’s independent panel [3] highlighted four elements that create these inequalities: real-world health inequalities and injustices, ‘baked-in’ discrimination in data, inequalities in clinical use and biased design and development. Very simplistically, inequities can arise due to a lack of access to a device or treatment etc. or due to biased performance and/or safety of a device that can be accessed. This technical brief will take a stroll through the phases of the medical device lifecycle and highlight some of the considerations that affect equity along the way. Bias Bias is currently much talked about in the context of artificial intelligence (AI) and machine learning (ML) enabled medical devices [15], but is not exclusive to those devices [16-19]. Bias of one form or another is typically a contributing factor for inequality in the MedTech industry, if not the root cause in certain cases. There are various forms of bias but the two of interest here are conscious and unconscious bias (also referred to as hidden bias or implicit bias). For the latter, our own upbringing, education, lifestyle, status, and preferences can unconsciously affect our decision-making and our analysis of outcomes or consequences. There have been numerous cases reported where bias in some form has led to inequality in health outcomes. For example: the inadequate suitability of crash test dummies based on male anatomy as surrogates for female car drivers and passengers [20]; the variable performance of pulse oximeters on different skin tones [21-23]; and the diagnosis of kidney disease based on creatinine levels in the blood of black patients [3]. At a very simple level, we also see this with the languages used in the information for safety supplied with medical devices. For obvious reasons, there is a drive to consolidate translations and have the information provided in as few languages as possible, with the default mindset often being ‘everyone can speak English,' but this could put many users at a disadvantage when it comes to using the device safely and user understanding of the residual risks associated with using the device. The potential for bias is also there in the intended use and intended user. If certain prerequisites are rightly placed on who can use the device, where it can be used and what other equipment and/or therapies need to be used in conjunction with the device, this can inadvertently restrict access to the device to only certain patient demographics (e.g. certain countries or specific socio-economic groups). Regulations as a Barrier Regulations should not be a barrier for devices that could positively impact health and/or quality of life of individuals, or, positively impact the healthcare system as a whole. Regulators (and the authors of regulations) should recognize the difficulty in obtaining clinical evidence for certain intended purposes or certain patient populations and not prevent those devices getting to market on the basis they cannot generate the same level of clinical data as more generic, widely used devices. With this in mind, regulatory frameworks should provide pathways for devices where there is uncertainty on the risk but also the real possibility of clinical benefit that cannot currently be achieved with other devices. Not all devices are the same, and so to treat them all in the same way can adversely affect those patients/users who would benefit most from devices that struggle to make it through a conformity assessment. With this in mind, ‘advancing health equity’ is in the FDA’s CDRH strategic priorities for 2022-2025 [24] (“Putting patients first is an empty promise if it only applies to some and not all”). The Breakthrough program is one example of how they are targeting health inequity [25] by trying to improve access to certain innovative and/or much-needed devices (although that is not to say that the program is working perfectly yet). To hear directly from the FDA on this initiative, sign up for (or watch on demand after 8 August 2024) our presentation and panel discussion: Advancing Health Equity with IVDs & Medical Devices. Be Part of the Discussion and Join Us Similarly in the UK, the Innovative Devices Access Pathway (IDAP) [26] has similar aims, although is still at the pilot stage. Lastly, proposals have been drafted for amendments to the EU MDR in relation to specific market access pathways for innovative devices and orphan devices [27]. As regulators look towards regulatory harmonization and the utilization of reliance and recognition pathways [28-29], they still need to consider equity. What are the risks (associated with equity of device safety and performance) that come from fast-tracking a device approved by one regulator into another country/region if that was never part of the original design and development? If the patient demographics in those countries are vastly different, or the clinical practice in which the device would be used is different, the patient outcomes could be adversely affected. That is not to argue against the use of reliance and recognition pathways, but you cannot control risks if you do not identify and openly discuss them. Product Concept Every finished medical device starts with a concept, an intended use, or a clinical need that needs to be addressed. Questions considered include: Which clinical needs are to be addressed? Which user needs are to be solved? Which patient populations are to be provided with an improved treatment option? Does the majority rule? Is it a case of whoever shouts loudest? The answers to these questions are often heavily affected by commercial factors, such as research funding availability, feasibility of regulatory pathways to market, cost (and timeline) for regulatory ‘approval,' return on investment, potential market value, relevant competitors, reimbursement options, and speed to market. This is understandable; most medical device manufacturers are businesses after all, and profits are needed for the next development project, etc. This even applies to research institutions who are reliant on government or charitable funding initiatives, and whose research may then be developed into a finished product via a spin-off, licensing agreement or acquisition. But what about those user needs that are not financially attractive? Or those clinical conditions that are not widely understood? This is not an area that should be decided by budget holders alone, as there needs to be a holistic view of the healthcare system in order to address this source of inequity. This also includes service provision at a national and local level, e.g. the inequity of a postcode lottery that determines which devices you can access based upon where you live. Access to funding for research and development related to underrepresented groups is part of the recommendations from the UK’s independent panel review [3]. Design & Development Once the concept has been confirmed and development begins, multiple sources of bias and inequity can creep in, usually unintentionally and unbeknownst to the project team. We identify risks and make design-decisions within the framework of what we know. Ideally, we would also investigate the topics that we don’t know to help that decision-making process, but... we do not always know what we do not know. The analysis of user/customer needs and their translation into design input requirements should involve the development team, all with their own preferences and unconscious bias on what is important. Decisions on which indications to target, which patient populations to cover, and which devices sizes/configurations to include, can all be subject to bias and thus result in inequity. Assumptions relating to the similarity or homogeneity of physiology and anatomy in different user populations (e.g. male to female, variability between different ethnic groups) is a form of unconscious bias. In adequate consideration of, or completely overlooking the variability in how a device might be used by different user populations or patient populations, is another form of unconscious bias (e.g. the user will always have access to certain supplementary therapies, or the patient will be supported and monitored on a monthly basis). Factors that could affect device performance, and especially those that could result in variable outcomes for different populations, should be identified as part of development. I personally would consider this basic good science and/or engineering, but at the least would expect it to be identified as part of risk management. The varying performance of pulse oximeters on patient with different skin pigmentations is an example of this. Similarly, AAMI TR 34971:2023 [15] calls out an example where differences in breast tissue density in different patient demographics was overlooked or misunderstood, resulting in unintentional bias in the breast cancer detection algorithm. Using simple risk analysis techniques to identify the characteristics related to safety (see ISO 14971:2019 §5.3 [30] and ISO TR 24971:2020 §5.3 [31]) can provide the framework to understand your device’s mode of action and the factors and/or variables that could inhibit the device’s ability to achieve its desired performance outcomes. Using the pulse oximeter as an example (acknowledging that hindsight is a wonderful thing): Light passes through the skin to the blood vessels in order to measure blood oxygenation. What are the layers of skin and their respective composition? How does skin structure and composition vary with age, race, ethnicity, underlying clinical condition, etc? Could those factors affect the passage of light? Will that produce variable levels of performance? Do we need to be transparent and communicate that to the end-user? Formative usability studies can be extremely powerful in understanding user preferences, potential use errors and areas for design improvement, but performing formative usability studies is not typically a regulatory requirement, nor a requirement for market access. Unconscious bias and cost (of course) play their part in decisions on the planning for formative usability studies. The selection of participants for such studies will inevitably affect the study outcome, and potentially bias downstream decisions based on the opinions, preferences, and ideas of the participants. Apparently simple considerations such as “do we need a mix of left-handed and right-handed study participants?” may be overlooked in the maelstrom of the development process. Decisions on how to finalize the user interface, set specifications, and resolve issues can be affected by the preferences of individual team members or be influenced by the phenomenon of group think (a form of cognitive bias). As mentioned earlier in this brief, the availability of the information for safety in only selected languages may inadvertently lead to different outcomes. This is partly why most national competent authorities stipulate, in their regulations or guidance, the languages required for information supplied to users in that specific country. Symbols may be used to replace written information, but the understanding of graphical symbols is heavily reliant on context (e.g. see whether someone under the age of 18 knows that the ‘save’ icon in various applications is a representation of the, now archaic, floppy disc). The user’s experience and knowledge affect whether they can comprehend the meaning of a symbol. Even symbols presented in ISO 15223-1:2021 [32] may have been grandfathered in from EN 980 and so their ‘validation’ comes more through exposure and familiarity over time rather than a demonstration that users can understand the information based on the graphical symbol alone. Symbol development requires various design options and iterations to optimise the symbol’s ability to be comprehended and associated with the desired meaning. Even then, users from different backgrounds, professions, and regions may not always interpret the symbol as it was intended, hence, why it is good practice to provide the meaning of symbols in text somewhere within the information provided by the device manufacturer. Once the device design is locked, frozen, or whatever your preferred term is, we move into Design Verification and Design Validation. The ideal (for lovers of objective evidence and data analysis) would be for every model, variant, size, configuration, and production line to be tested, validated, etc. for every use case, indication, patient population, and use environment. With that said, we have to be realistic about what is viable in the context of the resources required to achieve that ideal state. ISO 13485:2016 §7.3.6 and §7.3.7 [32] both require documented plans for the design verification and design validation methods and the applicable acceptance criteria. This includes the justification for statistical sampling, which commonly involves choices on worst case and/or representative test samples to reduce the volume of testing (often due to cost and duration). This choice leaves us with device variants, configurations, and sizes that may go untested before entering the market. With that lack of testing comes another fragment of uncertainty. Similarly for summative usability studies, clinical investigations, and performance studies, there is a balance to consider: generating sufficient objective evidence versus the cost and duration. Study designs need to consider: representative devices (configurations, sizes), representative users and patient populations and representative use environments/use cases. While this can sound easy to address, it is widely reported that women are underrepresented in clinical investigations/trials for medical devices [34-35]. Planning also needs to consider what clinical data is already available, is further data required, what is feasible to collect and what patient demographic data might be relevant to see correlations between patient characteristics/demographics and clinical outcomes. These considerations are more critical for clinical investigations and performance studies (than summative usability studies) due to the requirements and restrictions, including the ability to conduct studies on vulnerable populations (e.g. pregnant women, breast feeding mothers, paediatrics). Factors to consider when planning for study enrolment include: Demographic characteristics E.g. Race, Ethnicity, Sex, Age group Clinical characteristics E.g. Presence of comorbidities, disease etiology Socio-economic characteristics Access to care (preventive, diagnostic, treatment) In the US, the FDA have been active in updating existing guidance and creating new guidance regarding the diversity of study participants; and the collection and subsequent analysis of participant demographic data. This activity includes a recently updated draft of the guidance on Diversity Action Plans [11], which are intended to outline the study sponsor’s enrolment goals disaggregated by race, ethnicity, sex and age group as a minimum. The UK’s Health Research Authority is undertaking a similar improvement exercise [36]. We'll be discussing Diversity Action Plans and more with the Michelle FDA in an 8 August 2024 presentation and panel discussion: Advancing Health Equity with IVDs & Medical Devices. Be Part of the Discussion and Join Us Is it possible, ethical, and/or viable to conduct pre-clinical testing and clinical investigations for all intended users, patient populations, indications, use cases, and use environments, for each of the available device variants, configurations, and sizes? No, not really. In many cases, such exhaustive efforts may produce no additional benefit in terms of understanding the device’s performance and/or safety. Regulators do recognize that to an extent, but they have also recognized the uncertainty in performance outcomes when decisions on conformity are based solely on representative samples and/or equivalence with predicate devices. This is part of the reason for increased focus on post-market surveillance activities in the EU Medical Devices Regulation (MDR) 2017/745 and In Vitro Diagnostic medical devices Regulations (IVDR) 2017/746. If it is not realistic or feasible to generate that exhaustive level of objective evidence, where does that leave us in terms of equity? Benefit Risk Evaluation & Release to Market Most regulatory frameworks for medical devices require an evaluation of the device’s overall safety, and many are moving towards a formal evaluation of the benefits and risks as part of that evaluation. To this author’s knowledge, equity in outcome is not explicitly identified as a topic unless it becomes apparent in the evaluation of the clinical data. First of all, the benefit risk evaluation requires a grounding in the context of the generally acknowledged state of the art into which the device is entering/existing. Unconscious bias can creep in here, either through the desires of manufacturers to benchmark their device against a competitor or from the conformity assessment body imposing their own expectations of each new device meeting or exceeding the performance of what went before. Both of these example situations can see device functions, indications, or intended patient populations omitted, and thus remove the potential benefit for certain populations. Holistically, the benefit risk evaluation appraises the evidence (clinical, pre-clinical, and real-world) to support the safety and performance of the device. Ultimately, a decision is made on whether the benefit risk profile of the device is acceptable. If the data used in this decision-making process carries uncertainty and inherent bias, then there is greater uncertainty around the equity of the device’s safety and performance for all intended users/patients. Considerations include: Has the data been disaggregated to consider different patient/user demographics? Have patient/user preferences been considered as part of risk acceptability criteria? Have confounding variables (e.g. socio-economic status or access to healthcare) been considered when analyzing the data? From an EU perspective, the MDR and IVDR require device manufacturers to define and justify the clinical evidence that is sufficient for their device, and thus clinical evidence forms a large part of the benefit risk evaluation. Even this decision on what is sufficient can be affected by bias. For example, in the preference of the manufacturer and their tolerance for risk/uncertainty in their regulatory submission and overall time to obtain a CE mark. Additionally, the acceptance of the manufacturer’s rationale by their Notified Body can vary (who is considering: consistency across multiple manufacturers and device types; the preferences of their responsible Competent Authority; and the potential liability issues for any apparent safety issues that are overlooked). Both of these examples can lead to indications for use and/or patient populations/sub-populations, that are harder to gather data on, being omitted from applications without full consideration of those populations left behind. Recent guidance from the EU’s MDCG [37] has helped to clarify terms such as ‘orphan devices’, ‘orphan populations’ and ‘orphan subpopulations’, as well as guidance on the considerations for clinical evidence in these cases. The MDCG guidance cannot provide legal exemption from the requirement to perform clinical investigations on specific classifications of orphan devices. It does, however, reinforce the mindset that uncertainty in performance and safety is acceptable (with justification) at the point of market entry but it must be supported by thorough post-market surveillance activities to reduce that uncertainty where feasible. Once the product is ready to be released to market, there is also the matter of the information supplied by the manufacturer to the user/patient. There are several equity-related aspects to consider here. The first and most obvious one is the usability of the information for different users, including the language (e.g. languages native to the intended users), fonts and font sizes, choice of symbols, use of diagrams and illustrations, and the use of colours (e.g. combinations of red and green akin to traffic lights is not so effective for the many that suffer from colour blindness). A second consideration is the form of the information in terms of accessibility. This depends on the intended user and should be relevant and useful to them (e.g. devices intended to be used in the home by elderly users should consider that mobile apps or web-based instructions may not be the most suitable for the intended audience). A third consideration, I would not be so definitive to say “the final consideration," is transparency. By this, I mean the transparency of residual risks communicated to the intended users and patients (e.g. in the instructions for use, in sales brochures, in the Summary of Safety and Clinical Performance required in the EU). If residual risks or performance limits are known to differ depending on the intended use population, indication, use case, or use environment, then this information should be translated to the intended users/patients to enable them to make informed decisions about the acceptance of the residual risk before they use the device or agree for the device to be used on them. This latter point is summarized neatly by the FDA, MHRA, and Health Canada in their recent guiding principles for transparency for machine learning-enabled medical devices [38]; the principles of which can be adopted for all medical devices too (where they are relevant). Post-Market Surveillance What has post-market surveillance got to do with health equity, I hear you ask? Quite a lot. It is likely to be the lifecycle phase where health inequity becomes most apparent, but only if you are looking for it in the right places. In the reality of initial market entry on the back of testing of representative devices, post-market surveillance is where a device manufacturer should be highlighting those weak spots in data for clinical performance and safety, those areas of uncertainty that were accepted, and transferring that into the scope of post-market surveillance activities. The variables (e.g. patient sub-populations, use environments, use cases, regional differences in clinical practices) and the known risk factors should all be monitored as part of complaint trending. The FDA moved to support this with the addition of patient demographic fields in the MAUDE database, including patient age, sex, ethnicity, and race [12-14]. A device manufacturer’s complaint handling processes, coding structures, trending mechanisms, and reporting tools should be mindful of the need to be able to spot such trends. For example: Do your complaint reporting forms include patient/user demographic data that can be used for trending? Are there regional or national restrictions on what patient/user information can be gathered to facilitate trending? Does your complaint trending mechanism allow you to determine if there are trends related to patient/user characteristics or demographics, such difference in event types of occurrence rates between different user populations or from one country to another? In certain cases, e.g. weaknesses in the demonstration of clinical benefit over a period of time, those variables and risk factors should form the backbone of post-market clinical follow-up (PMCF) efforts in which additional clinical data is gathered. As in development, the design of post-market studies should consider the need to include participants that are representative of the user populations and the variations within. If PMCF studies are leveraging device registry data, consideration should be given to whether the registry has input data that is representative of the target populations (users and patients). Just like with machine learning enabled medical devices, a biased input is likely to skew the output of the data analysis. Similar to the complaint handling process, consideration should be given as to whether the registries actually collect (mandatory or voluntary) patient demographic data (or even user demographic data) to allow further analysis for those potential trends. Only with the collection of this real-world data, and the re-evaluation of benefits and residual risks for the device’s target populations and indications for use, can a manufacturer reduce the uncertainty in their disclosure of benefits and residual risks to patients, users, regulatory authorities, and customers. What You Can Do This is a huge topic and thus there is a need for cumulative and incremental improvement actions rather than one grand gesture. This includes: Regulatory authorities should ensure that realistic pathways to market are available for those devices where it is difficult to gather extensive clinical data. Device manufacturers should: Evaluate how they collect, solicit, analyze, and incorporate user and patient feedback during development and post-market surveillance. Whose opinions are being sought? Are they representative of the intended users and intended patients? Use the Design Input and Risk Analysis portions of your development processes wisely and effectively. Take the time to understand the intended use, the intended clinical environment, and the varying factors that contribute to, or could affect, the successful operation of your device. Identify gaps in knowledge about variability in the physiology and anatomy, etc. of the intended patient populations and/or etiology of the disease/condition of interest, and consider collaborations with suitable research institutions (e.g. universities, teaching hospitals) to gather such data. Consider the use of independent experts (e.g. representatives from patient advocacy groups, technical experts, front line clinicians) during design and development reviews can counter the cognitive bias that may occur within a development team. Be considerate of how the different device sizes, variants, etc. relate to different patient populations and user groups when planning design verification and design validation testing and selecting representative samples for testing. Consider the relevant patient and user populations when designing pre-market clinical studies and usability studies. Consider the use of auditors from outside the business unit or from another site, or from outside your company, for internal audits of quality management systems and technical documentation in order to provide a fresh pair of eyes and a different perspective on your actions and decision-making. Ensure that clinical data is disaggregated to enable analysis of whether the clinical outcomes differ for different patient populations and/or sub-populations. Embrace the guidance on diversity in clinical investigations and consider the spectrum of patient demographics that should be represented in the study. Be clear and transparent with regards to residual risks and claims over performance, especially where data has been extrapolated to support broader populations. Ensure that risk factors and suspected variables are carried through into post-market surveillance activities. Consider how patient/user demographic data can be gathered as part of collecting post-market surveillance data to enable disaggregation of the data and analysis of trends within specific patient populations. Final note: Just after the publishing of this technical brief, the FDA published their discussion paper on this topic [39]. More RQM+ Resources Register for (or watch on demand after 8 August 2024) our RQM+ Live! presentation and panel featuring FDA CDRH Acting Director and Deputy Center Director for Transformation, Michelle Tarver, M.D., Ph.D. Be Part of the Discussion and Join Us Watch our video series on strategy and tactics for clinical studies Watch our on-demand webinar on The Critical Role of Communication in Risk Management Revisit our Live! show covering MDCG 2023-7: New Clinical Evidence Pathways for Legacy and New Devices Follow RQM+ on LinkedIn for all of our updates References Health equity (WHO) Guiding Principles to Support Medical Device Health Equity (IMDRF, 8 Feb 2024) Equity in medical devices: independent review - final report (11 Mar 2024) MHRA response to Equity in Medical Devices: Independent Review (MHRA, 11 Mar 2024) Racial and Ethnic Minority Acceleration Consortium for Health Equity (REACH). OMHHE Enhance Equity Research Hub Racic A et al. Health equity as a strategic priority: FDA and Health Canada initiatives. Regulatory Focus. Published online 11 April 2024. FDA Launches Health Care at Home Initiative to Help Advance Health Equity (FDA, 23 April 2024) Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies (FDA, 5 Feb 2018) Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products (FDA, 29 Jan 2024) Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies (FDA, 26 Jun 2024) About Manufacturer and User Facility Device Experience (MAUDE) Database (FDA, 6 Jun 2024) FDA Collects More Demographics Data In MAUDE (MedTech Insight, 23 Oct 2023) Unpacking Averages: Device Manufacturers Should Use the Newly Released Demographic Data in MDRs to Ensure Their Devices Are Not Disproportionately Hurting Minorities (Health Law Advisor Blog, 6 Feb 2024) AAMI TIR 34971:2023 (BS/AAMI 34971:2023) - Application of ISO 14971 to machine learning in artificial intelligence. Guide Considerations for addressing bias in artificial intelligence for health equity (Abràmoff et al, npj Digital Medicine (2023) 6:170) Technology must tackle bias in medical devices (Guardian, 19 Mar 2024) From oximeters to AI, where bias in medical devices may lurk (Guardian, 21 Nov 2021) Combating Bias In Medical Innovation (Federation of American Scientists, 26 Apr 2022) Visible Women With Caroline Criado Perez | Episode 4: Why Cars Aren’t Safe For Women FDA warns about limitations and accuracy of pulse oximeters (FDA, 19 Feb 2021) Limitations of pulse oximeters and the effect of skin pigmentation (TGA, 7 Jan 2022) The use and regulation of pulse oximeters (information for healthcare professionals) (MHRA, 26 Mar 2021) CDRH 2022-2025 Strategic Priorities (FDA, 5 Apr 2024) Breakthrough Devices Program (FDA, 14 Sep 2023) The Innovative Devices Access Pathway (IDAP) (MHRA, 29 Feb 2024) Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Regulations (EU) 2017/745 as regards amendment of the certificate duration IMDRF Meeting March 2024, presentations on reliance Statement of policy intent: international recognition of medical devices ISO 14971:2019 Medical devices - Application of risk management to medical devices ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO 14971 ISO 15223-1:2021 Medical devices - Symbols to be used with information to be supplied by the manufacturer - Part 1: General requirements ISO 13485:2016 Medical devices — Quality management systems — requirements for regulatory purposes Women’s Representation in RCTs Evaluating FDA-Supervised Medical Devices. A Systematic Review (Epstein NK, Harpaz M, Abo-Molhem M, Yehuda D, Tau N, Yahav D. JAMA Intern Med. Published online June 10, 2024) Women in Clinical Trials: For Patients (FDA, 16 May 2024) Increasing the diversity of people taking part in research (UK NHS Health Research Authority, 20 Mar 2024) MDCG 2024-10 Clinical evaluation of orphan medical devices (MDCG, June 2024) Transparency for Machine Learning-Enabled Medical Devices: Guiding Principles (FDA, MHRA, Health Canada, 13 June 2024) Discussion Paper: Health Equity For Medical Devices (FDA, 8 August 2024) #### Understanding Extractables and Leachables Extractables and leachables are potentially hazardous chemicals that a patient can be exposed to when using medical devices or drug products. These chemicals may be present as impurities in the materials used, but also may be introduced during manufacturing or storage.  Management of the risks that these chemicals pose to patients can be managed, but requires robust quality control and careful study design. The cost of getting it wrong could include unexpected performance of the device or drug product due to these chemicals, plus the regulatory non-compliance issues that result. At worst, leachables may prove toxic to end-users, posing serious health risks. Part of any robust pharmaceutical or medical device manufacturing process is a risk assessment that considers not only the product and included materials but also the manufacturing environment, any needed packaging materials, and the potential alterations resulting from sterilization procedures. Because leachable chemicals can be the result of complex interactions between both intentionally added and unanticipated chemicals, evaluation of the materials being used must be bolstered by a carefully designed laboratory study (often referred to as chemical characterization of extractables and leachables or simply E&L).Extractables and leachables refer to compounds which can be either extracted or leached from a container into a drug formulation or from a medical device contacting a patient. Extractables: Compounds that can be extracted from the container closure system under specific laboratory conditions — typically more aggressive than the use condition. Leachables: Compounds that leach into the drug product formulation from the container closure as a result of direct contact with the formulation, or compounds that a patient may be exposed to through contact with a medical device. What are Extractables? Extractables are chemicals which can be extracted when in contact with a solvent as part of a laboratory study. To study the risk of  a wide range of chemicals to be extracted, experiments are done generally using a range of solvents such as basic, acidic, aqueous and organic solvents in addition to using elevated temperature to increase extraction rates. It is critical that the process of extraction does not alter or degrade the material of interest. In the resulting extracts, compounds which are present are known as “extractables” and studies are designed to result in a worst-case estimate of exposure to the patient. This can aid in materials selection and early risk assessment. When a study is properly designed, the expectation is that all observed extractables are potential leachables. What are Leachables? Leachables are chemicals that are introduced into the product during conditions more closely resembling drug product storage conditions or clinical use of a medical device. However, especially for implantable medical devices, the conditions the device is exposed to cannot be replicated in the laboratory.  For these studies, the laboratory must consider carefully the nature of the device to design an appropriate simulated leachables experiment.For drug products, it is necessary to evaluate the potential evolution of leachables during the shelf-life of the product (stability leachables).  These studies are carried out to understand leachables which migrate under simulated environmental conditions. In these studies it is important to consider the possibility that the leachable interacts with the drug product itself, forming new  ‘secondary leachables’. How are Extractables and Leachables Detected? There are a range of analytical techniques that can be used to identify extractables and leachables. Volatile organic compounds are frequently analyzed using headspace GCMS. Semi-volatile organic compounds are usually assessed employing GCMS. Semi-volatile and Non-volatile ionizable organic compounds are typically analyzed with HRAM LC-MS/MS and elemental impurities are identified using ICP-MS.Typically, for screening surrogate reference standards are used to quantify these compounds and a toxicologist provides a risk assessment based on the extractables which fall above the analytical evaluation threshold (AET). The process involves steps like acquiring background information, designing the study, preparing samples, extraction, identification, quantification, and toxicology evaluations.  For drug container closure systems, leachables monitoring requires further development, resulting in validated quantitative methods for monitored chemicals. It is crucial to select samples carefully, choose appropriate solvents for extraction, include analysis blanks and control samples, and identify unknown compounds during the process. Extractables and Leachables from RQM+ Lab Services RQM+ offers a wide range of laboratory services to clients in the pharmaceutical, medical device, food and beverage, agricultural industries, among others. Our services include detection and identification of contaminants, analysis of packaging materials, deformulation, physical testing, contamination and failure investigations, and more. We also provide expert witness services for litigation cases involving product failures, liability issues, patent infringements, and more. We partner with our customers to create studies backed up by over 40 years of experience. Download Our White Paper: Are We Equipped to Handle a PFAS-Free Future? To find out more about how we can help with extractables and leachables, contact us today. #### Unveiling MDCG 2023-7: Equivalence, Clinical Investigations and Data Access Under EU MDR Introduction to the New MDCG Guidance A new MDCG guidance document has been published today, providing welcome clarification regarding the practical application of EU MDR Articles 61(4) – (6). This new guidance, "MDCG 2023-7: Guidance on exemptions from the requirement to perform clinical investigations pursuant to Article 61(4)-(6) MDR and on ‘sufficient levels of access’ to data needed to justify claims of equivalence" opens up strategies and pathways that many assumed were blocked off under EU MDR, and sheds new light on the following: when contracts are or are not required to claim equivalence to (and therefore use the associated clinical data from) another manufacturer’s device; when implantable and class III devices can be exempted from the statutory requirements for clinical investigations (per Article 61(4)); what “sufficient levels of access” to the data required to justify claims of equivalence (per Annex XIV Section 3) looks like. Understanding Contract Requirements and Equivalence Claims On the first point above, what will be surprising to many is the confirmation that contracts are never required to claim equivalence with another manufacturer’s device. However, caveats apply: for implantable and class III devices, a manufacturer may still be required to undertake clinical investigation(s), regardless of the strength of their clinical evidence package, unless one of the four exemption cases described in Articles 61(4) – (6) applies. In short, the key clarification the guidance makes is that Articles 61(4)-(6) are not defining when equivalence may or may not be used, but rather when implantable and class III devices may be exempted from the requirement for premarket clinical investigations. This may sound like the beginning of a semantic argument, but there are important ramifications to this clarification which should significantly reduce barriers to market for many implantable and class III devices. Practical Implications for Implantable and Class III Devices What it means in practical terms for implantable and class III device is: For the legacy MDD and AIMDD devices described in Article 61(6)(a), and the listed WET devices in Article 61(6)(b), the clinical evaluation can include data from another manufacturer’s demonstrated equivalent device, without a contract, in the clinical evaluation of their own device. If all of the conditions of these Articles are met, the manufacturer can place these devices on the EU market without undertaking pre-market clinical investigations. The guidance also clears up a frequent point of confusion: Both Article 61(6)(a) and 61(6)(b) include a requirement that the clinical evaluation is “based on sufficient clinical data”. Some have assumed that this means “clinical data on the subject device, not from equivalent devices” – but the guidance very clearly explains that any clinical data within the definition of clinical data in Article 2(48), including equivalence data, is acceptable. Equivalence data could therefore form part, or all, of the clinical evidence package submitted to demonstrate conformity with the relevant safety and performance requirements per Article 61(1). Similarly, for devices which are modifications of (a) device(s) already marketed by the same manufacturer, and meet the other conditions described in Article 61(4) bullets one to three, clinical data from another manufacturer’s device can be included in the clinical evidence package. Although Article 61(4) bullet two requires that “the clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements”, the guidance explains that “The MDR does not prohibit the use of data from another manufacturer’s [equivalent device] in the clinical evaluation of the manufacturer’s already marketed device.” Data from another manufacturer’s equivalent device can even be used without a contract in what is described as exemption CASE 4, where the manufacturer has a contract with at least one manufacturer. The utility of this is somewhat limited however, as data from additional manufacturers’ devices can only be used to support the same indications covered by the contract. Finally, in the case where the device is class III or implantable and none of the exemption cases apply, and therefore premarket clinical investigations are mandatory, the guidance indicates that here too, clinical data from another manufacturer’s equivalent device can be used, without a contract, alongside clinical data gained from the clinical investigation(s). Analyzing the Exemption Cases and Their Impact This flexibility reflects the lower risk associated with each of these cases, that justifies the exemption from the requirement for clinical investigations that is applied to implantable and class III devices by default. In other words, with respect to the CASEs described in the guidance: CASE 2: if your device has been previously certified under the Directives, it will have several years’ market experience, and likely data from PMCF, during which safety or performance issues should have been identified. In addition, the majority of these devices (with the exception of some up-classified devices previously placed on the market under quality systems certification only) will have had a design examination or renewal within the last five years. Within this period, requirements for clinical data and post-market surveillance had become significantly stricter, and application of guidance such as MedDev 2.7/1 rev 4 means that the conformity assessment would have been similar in rigour to current requirements under the Regulation; CASE 4: if you are relying on equivalence but have a contract with the manufacturer of that device providing full access to the technical documentation as per Article 61(5), it lessens the risk of unknowns related to device design, clinical results and adverse events, product changes, etc.; CASE 1: similarly, if your device is a design variant of one of your own devices, and you can demonstrate equivalence (as per bullets 1-3 of Article 61(4)) the risk of such unknowns is largely eliminated; CASE 3: finally, if your device is one of the listed WET of Article 61(6)(b), these devices are by their nature comparatively low risk, being standard of care and generally having a well-known safety and performance profile. Emphasizing the Role of Clinical Data in Device Safety and Performance This flexibility will be welcome to device manufacturers who may have been at risk of refusal or reduction of indications, with the clarity provided that they can use all forms of clinical data within the definition of Article 2(48) to demonstrate the safety and performance of their devices, including equivalence with another manufacturer’s device. It may also be useful for future product development, by expanding the pool of clinical evidence available to manufacturers. Note, however, two points regarding PMCF: the guidance explicitly states that, where PMCF studies were a condition of prior certification, these exemption cases cannot be used to justify failure to complete such studies; typically, when clinical evaluation is based in whole or in part on equivalence, there is an expectation that PMCF studies will be undertaken to ensure that clinical data of an appropriate quality will be collected on the subject device. Navigating 'Sufficient Levels of Access' to Data With respect to “sufficient levels of access” to the data required to justify claims of equivalence per Annex XIV Section 3, the guidance also clarifies that a contract is not the only means by which a manufacturer can demonstrate this. Appendix II of the guidance provides examples of other means, and suggests a hierarchy with respect to the completeness of access (and by extension, the likely strength of the justification that the level of access is sufficient). A few important points to note here: the guidance reinforces what is already clearly stated in Annex XIV section 3, but which has sometimes been a source of confusion: namely, access is required to the data needed to justify claims of equivalence (i.e, the clinical, technical and biological parameters of the claimed equivalent) and NOT to the totality of the technical documentation. (The occasional confusion may arise because Article 61(5) does require access to the full technical documentation, but as the guidance confirms, the requirements of Article 61(5) do not apply outside of that Article); a “level of access” is considered insufficient only if there are gaps in the completeness or expected accuracy of associated clinical, biological and technical data which would be considered to invalidate claims of equivalence; the table in Appendix II is provided for illustrative purposes only, and is not intended to be exhaustive or prescriptive. This point is made explicitly in Section 5 of the guidance, as well as in the footnotes to the table in Appendix II. This reminder should hopefully provide some flexibility to notified bodies to apply a risk-based approach when assessing the adequacy of access to data. Strategic Next Steps for MDR Conformity and Clinical Development If your technical documentation has not yet been submitted for MDR conformity assessment, or if it is still in the queue and awaiting notified body feedback, you may wish to review your clinical evidence package to determine if this could be strengthened through use of equivalence. If such is the case, it would also be advisable to review and update associated documentation such as risk or PMCF plans. For products still in development, review clinical development plans to determine if this new understanding could affect clinical investigation strategy or accelerate product launch timelines. Embracing these steps will position your organization at the forefront of compliance, ready to navigate the evolving landscape of medical device regulations with confidence and clarity. More EU MDR resources at your fingertips: Watch RQM+ Live! #75 Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers Watch RQM+ Live! #72 EU MDR Timelines and Fine Lines: Unraveling Critical Transition Nuances to Gain Compliance Read our two recent guides: Musical Chairs MDR-Style: Keep dancing even though the music has stopped Don’t Get Caught Off Guard: How to Meet the EU’s 2024 MDR Deadlines Follow #MedTechVoices on LinkedIn and get insights from our team as they analyze each of the opinions published by the Expert Panels as part of the Clinical Evaluation Consultation Process. Follow RQM+ on LinkedIn for all of our updates! #### Validating the Future of Neuromodulation: How Jordi Labs Supports Regulatory-Ready Innovation Neuromodulation technologies are changing how we treat conditions like chronic pain, epilepsy, depression, and movement disorders. From spinal cord stimulators to implantable brain-computer interfaces, these devices represent the cutting edge of MedTech innovation. However, their clinical potential is matched by significant regulatory scrutiny. Neuromodulation devices—often classified as Class III—must meet the highest standards for biocompatibility, material stability, and performance safety. Validation is thus the foundation of approval and market entry for MedTech companies. That’s where Jordi Labs, part of RQM+, comes in. By delivering high-fidelity analytical data and expert consulting, Jordi accelerates validation processes and helps innovators achieve regulatory readiness. Why Neuromodulation Requires Rigorous Validation Neuromodulation devices are designed for long-term interaction with the nervous system. As a result, regulators demand comprehensive validation to ensure safety and performance over time. Key validation requirements include: Full chemical characterization of body-contacting components Demonstration of long-term material stability under physiological conditions Verification of electrical performance, insulation durability, and signal reliability Proven biocompatibility in accordance with ISO 10993 standards Failure to deliver robust validation data can result in costly delays to clinical trials, FDA approval, or CE marking. Common Validation Challenges in Neuromodulation 1. Chemical Characterization Regulators require detailed extractables and leachables (E&L) profiles for every material that contacts the body. This includes coatings, insulators, adhesives, and wires.  For devices in this category, novel and/or complex materials are often used. Deep polymer chemistry expertise is required to ensure accurate results. 2. Material Stability Materials must maintain integrity over time—especially in dynamic environments like spinal or cranial cavities. Degradation, delamination, or leaching can compromise safety. 3. Device Aging and Degradation Understanding how neuromodulation devices respond to heat, moisture, bodily fluids, and electrical stimulation is crucial for long-term risk assessment. 4. Failure Investigation When devices underperform, manufacturers must identify and eliminate root causes. These may include process residues, contamination, or formulation instability. How Jordi Labs Enables Faster, Safer Validation 1. Expert-Led E&L Testing and Chemical Characterization Jordi Labs is an industry leader in E&L analysis, polymer chemistry, and unknown compound identification. Their proprietary methods are: Compliant with ISO 10993-18 and FDA guidance Frequently referenced in regulatory approvals Capable of detecting ultra-trace-level contaminants With over 60 analytical platforms—including LC-MS, GC-MS, ICP-MS, Headspace GC-MS, FTIR, and SEM—Jordi delivers actionable, submission-ready chemical safety data. 2. Support for Material Selection and Aging Studies Jordi Labs helps engineering and R&D teams select the right materials from the start—preventing costly redesigns later in development. Capabilities include: Screening polymers and metals for stability and biocompatibility Conducting accelerated aging to simulate long-term exposure Assessing chemical changes that signal performance degradation These insights help de-risk design choices and strengthen technical files. 3. Rapid Failure Analysis and Corrective Action Support When a device fails in testing or clinical use, Jordi responds with forensic-grade analysis to identify the root cause. Typical scenarios: Discoloration of encapsulants or coatings Unexplained residues or particles in packaging or on components Mechanical failure due to chemical degradation Degradation due to harsh sterilization conditions Their results inform corrective actions that reinforce both product safety and quality management systems. 4. Regulatory Documentation That Speaks Regulator Language Beyond testing, Jordi delivers polished reports aligned with regulatory expectations, streamlining the review process. Benefits include: Easy integration into FDA 510(k), De Novo, and PMA submissions Compatibility with EU MDR and IVDR requirements Reduced need for follow-up questions from agencies Clients report faster reviews and higher acceptance rates thanks to Jordi’s credibility and precision. Powered by Integration: Jordi Labs and RQM+ As part of RQM+, Jordi Labs offers more than analytical services—they’re part of a full-service consulting ecosystem that spans regulatory strategy, clinical development, quality systems, and market access. This integration enables: Early alignment between testing and submission strategy Seamless handoffs between scientific and regulatory teams Efficient, end-to-end support from bench to bedside Together, RQM+ and Jordi Labs reduce complexity, accelerate development, and improve outcomes for neuromodulation innovators. Closing Thoughts Validating neuromodulation devices requires more than lab testing—it demands scientific depth, regulatory fluency, and real-world agility. Jordi Labs delivers all three. Their advanced chemical analysis, combined with submission-ready documentation and strategic alignment through RQM+, helps MedTech teams move faster, smarter, and with greater confidence. As neuromodulation shapes the future of medicine, Jordi ensures that tomorrow’s breakthroughs meet today’s standards for safety and performance. #### We Make Women's Health Happen: Innovative Devices for Fertility Treatment Navigating fertility treatments can be a physically and emotionally demanding experience for women. As the sole child bearers, women are more directly impacted by procedures like in vitro fertilization (IVF), which require a significant toll on their bodies even before pregnancy begins. The initial stages often involve 2-4 weeks of fertility hormone treatments, frequently administered through multiple self-injections. Recognizing the stress associated with this process, RQM+ is dedicated to helping bring innovative solutions to market that can ease this burden. One example of RQM+'s impact in this area involves work on a novel injection device intended to make the self-injection process simpler and less painful for women undergoing fertility treatments. The goal of this project was to gain valuable regulatory insight from the FDA regarding the potential testing requirements for this innovative device and to narrow down the available regulatory pathways. A key challenge identified was the fact that this product was a “combination product,” integrating a device (the injector) and a drug (the fertility drug), which comes with unique regulatory considerations.   While the FDA has improved communications regarding combination product expectations, clarity on necessary evidence for novel products is still needed. To help overcome these challenges, RQM+ played a crucial role. Initially, RQM+ educated the client on the FDA’s current and typical regulatory expectations for drug delivery devices through a comprehensive regulatory strategy. Subsequently, RQM+ assisted in developing a meeting package to present to the Agency and facilitated a face-to-face meeting with the FDA to obtain critical feedback on the available regulatory pathways. In a follow-up interaction, RQM+ submitted a meeting package and secured written feedback from the Agency concerning preclinical and clinical expectations. This critical feedback obtained by RQM+ was vital for the client’s product development process, helping to accelerate market access for a treatment designed to ease the strain of an already overwhelming process for women.   By facilitating this engagement with the FDA, RQM+ helped to ensure that this less painful and streamlined technology could potentially reach women sooner, alleviating some of the physical stress associated with necessary injections in fertility treatments and the psychological stress of tracking multiple treatments.  Stay tuned later this week for part two of this series, "Addressing Unmet Needs in Women's Health: Devices for Mental Health Support," where we'll delve deeper into the critical unmet needs in women's mental health and explore how innovative medical devices and combination products can offer much-needed support. Discover how RQM+ leverages its collective expertise to navigate the complexities of product development and regulatory processes, accelerating the path to market for solutions that can make a real difference in women's lives. Don't miss out on this insightful discussion!  In case you missed this month's RQM+ Live! panel discussion, access the webinar on demand to hear industry leaders and regulatory experts share real-world strategies MedTech companies can use to navigate these barriers and bring life-changing innovations to market. #### What Are Clinical Benefits and How Do You Evaluate Them in Your CER? The rollout of the EU MDR has created new challenges for medical device manufacturers, including those that have had devices on the market for a long time. One area of increased focus is the need to quantitatively establish the clinical benefits to patients from the device based on relevant and specified clinical outcome parameters. This requirement is being strictly enforced by notified bodies and, although this can be straightforward for some types of devices, for others, it can be difficult to define the benefits to the patient. Unfortunately, most clinical evaluations only focus on clinical safety and performance, and the clinical benefit to the patient is often left out. This results in questions from the notified body and significant updates to the clinical evaluation during the review, which can be stressful and lead to longer review times. Understanding the clinical benefits of your devices and ensuring they are incorporated into your clinical evaluation reports is an essential component of MDR compliance.   Definition of Clinical Benefit EU MDR Article 2-53 defines a clinical benefit as: “The positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health.”  In other words, a clinical benefit is essentially the improvement the patient is expected to experience as a result of the device.  It’s important to note that this is different from the performance of the device, which is the ability of the device to achieve its intended purpose. MDCG 2021-6 provides a clear delineation between clinical performance and clinical benefit. However, clinical benefits and performance are related, since as noted in MDCG 2020-6, the clinical performance is the ability of the device to achieve its intended purpose, thereby leading to a clinical benefit. MDCG 2020-6 provides further guidance pertaining to clinical benefits, noting that: “Clinical benefits may be either direct or indirect; for example devices such as guidewires may assist other medical devices in achieving their intended purpose, without having a direct therapeutic or diagnostic function themselves.”  MDCG 2020-6 also notes that, while direct clinical benefits should be supported by clinical data, indirect clinical benefits may be demonstrable by other evidence, such as preclinical and bench test data, real-world data such as registries, and data from another device that is used with the subject device that does have direct clinical data. For example, the data about a stent can be used to justify the safety and performance of a guidewire.  Examples of Clinical Benefits Direct clinical benefits are fairly straightforward and usually easier to associate with specific clinical outcome parameters. For example, a total hip replacement has clear and direct clinical benefits to the patient: reduction of pain and improved hip function. These can be measured using various clinical measures, such as Harris Hip Scores. Indirect clinical benefits, however, are more difficult to define and link to specific clinical outcome parameters. For example, surgical instruments used in a hip replacement procedure don't necessarily have a direct clinical benefit. This is where we look to indirect clinical benefits. The instruments facilitate the procedure, so we can look to the hip replacement procedure outcomes as the indirect clinical benefit. This is where the second part of the MDR definition for clinical benefits—“or a positive impact on patient management”—is helpful. In these cases, it may make more sense to utilize nonclinical testing, such as usability testing, along with the procedural success rate in the clinical evaluation. For example, the clinical benefit of an implant sizer may be demonstrated by the successful completion of the procedure without any sizing issues. If there were no sizing issues, there was a benefit to the patient by enabling the surgeon to determine the proper size of the instrument in a timely manner, thereby minimizing procedure time and increasing the likelihood of successful performance by the implant. Practical Tips for Defining Clinical Benefits Just do it.  The most important tip for defining clinical benefits is simply to do it. If you ignore this part of the regulation, notified bodies will ask why it’s missing. Even if it is challenging to define the clinical benefit from the device, it is important to consider the requirement and have a clear plan for demonstrating either an indirect or direct clinical benefit. Follow the guidance.  Refer to MEDDEV 2.7/1 rev 4, MDCG 2020-6, MDCG 2020-13, and other guidance documents to help understand clinical benefits and what notified bodies will be looking for in the clinical evaluation. Check for gaps. Optimize your technical documentation to ensure that clinical benefits are defined consistently in all of the required areas. There is a lot of crossover in the various documentation required by MDR, and if information is missing or inconsistent, it can lead to more questions from the notified body and longer review times. Take the time to closely review and cross-reference your documentation against the requirements before submitting it to save time and resources.  RQM+ Is Here to Help Defining clinical benefits is just one piece of the puzzle when it comes to MDR compliance. If your team is overwhelmed or if you want the benefit of the expertise from former notified body leadership on your side, our team is here to help. If you’re struggling with clinical evaluation reports or a particular section of your application or want to make sure you have everything covered, start with our MDR Filtering Tool. This interactive tool allows you to quickly find all references to clinical benefits (and any other topic) in the MDR in every chapter, section, and article.    #### What are the Key Clinical Trial Therapeutic Areas? Medical innovation is built on the bedrock of clinical trials. They address the complexities of treatment development, therapeutic efficacy, preventive care, and so on. However, certain therapeutic areas demand specific focus due to their widespread health impact and intricate challenges. Focusing on key clinical trial therapeutic areas helps guide resource allocation, ensure alignment with unmet patient needs, promote real innovation, and ensure significant progress in treatments with improved global healthcare outcomes. In our experience at RQM+, the following therapeutic areas tend to be included in many of the trials we work on. Oncology Cancer-associated clinical trials are a cornerstone of clinical advancements, addressing the urgent need for more effective, patient-specific therapies. The intricate challenges posed by over 100 distinct cancer subtypes create unique challenges for oncology trial study design and execution. Besides treating the cancer itself, many innovations focus on reducing treatment side effects or helping the healing process after potential surgeries be less burdensome to the patient. While the trial itself may not focus on the cancer treatment, being able to understand the patient population and associated data is essential. Respiratory Care Respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, continue to affect millions worldwide, imposing significant healthcare challenges and economic burdens. Clinical trials in this domain are valuable, advancing the development of novel therapies, state-of-the-art inhalation devices, and more precise diagnostic tools. General Surgery Surgical advancements are at the forefront of medical innovation, relying on robust clinical trials to evaluate new techniques, cutting-edge devices, and optimized perioperative care strategies. These trials are crucial in improving patient outcomes, reducing surgical risks, and enhancing recovery protocols. General surgery studies face unique challenges, including recruiting diverse patient populations, managing logistical complexities, and establishing measurable outcomes. Addressing these challenges requires meticulous study design and execution, ensuring trials yield reliable and actionable data. With advancements in minimally invasive techniques, robotic-assisted surgeries, and enhanced recovery pathways, clinical trials in this field paves the way for transformative improvements in surgical care, ultimately benefiting healthcare providers and their patients. Women's Health Women's health trials encompass a diverse array of conditions, including reproductive health, pregnancy-related complications, and menopausal therapies. These studies are critical in addressing gender-specific health needs, often requiring nuanced approaches and a commitment to ethical and patient-centered practices. Trials in this field explores new treatments and advances understanding of conditions that uniquely or disproportionately affect women. Such trials often demand expertise in managing complex factors like hormonal variations, societal stigma, and physiological diversity across different life stages. By focusing on these intricacies, clinical trials in women's health drive progress toward more personalized, effective, and inclusive care solutions that improve women's outcomes globally. Infectious Diseases The COVID-19 pandemic underscored the critical importance of clinical trials in infectious disease management. Whether developing vaccines, antivirals, or diagnostic tools, infectious disease trials demand rapid execution without compromising on quality.  Executing infectious disease trials requires adeptness in agile trial designs, risk-based monitoring, and global regulatory compliance to expedite time-sensitive studies. Orthopedics and Spine Orthopedic and spine trials focus on interventions for arthritis, fractures, and spinal deformities. These studies often involve surgical devices, biologics, and rehabilitation therapies and frequently require long-term follow-up (e.g., implant survivorship over 10+ years). Additionally, use of subjective outcome and quality of life surveys requires purposeful implementation and regular review to ensure the data are telling the true story. Urology Clinical trials in urology address conditions like urinary incontinence, kidney stones, and prostate cancer. These studies require precise methodologies and a deep understanding of patient needs. Additionally, treatments, side effects, and safety risks will differ with males vs. females which requires proficiency in both. As with Orthopedics, many outcomes are subjective and variable and requires expert management. Neurology Neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy, present profound challenges in clinical trials due to the intricate nature of the brain and the subjective variability of many clinical endpoints. These conditions demand innovative trial designs that account for the complexities of neurobiology and the individualized progression of symptoms. Advances in wearable technologies, digital biomarkers, and imaging techniques are transforming neurology trials by enabling more precise data collection and real-time monitoring. Patient-centric approaches, which consider the lived experiences of individuals and their caregivers, are essential for capturing meaningful outcomes. By embracing these methodologies, clinical trials continue to drive breakthroughs in understanding and treating neurological disorders, offering hope for improved therapies and quality of life for millions worldwide. Wound Care Wound care trials focus on developing treatments for chronic wounds, burns, and post-surgical recovery, to name a few. These studies require rigorous methodologies to assess efficacy and safety. Wound care practices can vary widely across sites and regions, which leads trial teams to ensure strict protocols that may be outside standard of care for some participating sites. Introducing blinding into the study (blinded assessors, for example) may help reduce bias in evaluating wound care success (or lack thereof). Ophthalmology Ophthalmology trials address conditions such as glaucoma, macular degeneration, and dry eye syndrome. These studies often involve innovative treatments, surgical techniques, and diagnostic tools. These diseases require familiarity with both systemic and ocular health as well as the specialized diagnostics. The patient population, often elderly for some conditions, may face mobility issues, making frequent site visits difficult. Tailored approaches are critical to ensuring complete and adequate data sets. Why Choose RQM+? At RQM+, we specialize in precision-driven solutions when designing and executing clinical trials. Our deep understanding of global regulatory landscapes, innovative strategies, and patient-centric approaches sets us apart. We address critical challenges in patient recruitment, endpoint definition, and safety oversight requirements with a comprehensive, tailored approach. This allows us to prioritize rigorous data collection and comprehensive analysis, ensuring the integrity and relevance of study outcomes. RQM+ is committed to excellence in clinical trial management across therapeutic areas. We understand that trials will require different approaches and don’t bring a one-size-fits-all solution. Our processes are written to be flexible, allowing our team to expertly conduct trials across all therapeutic areas listed, and more. From highly complex studies with enrollment of 1-2 subjects per month, to time-sensitive assay studies with enrollment of 50+ subjects per day, RQM+ is equipped to support your team through every step of the process. Whether you're addressing prevalent conditions or pioneering treatments for niche markets, RQM+ ensures your clinical trial is positioned for success. Visit our clinical trial therapeutic areas page to learn more about how we can support your therapeutic area. Together, we can advance healthcare and deliver transformative solutions to patients worldwide. For more reading - Finding Clinical Trial Support for Different Therapeutic Areas #### What Can You Gain From Full-Service MedTech Consulting? Launching a medical device or diagnostic in today’s complex global market requires far more than innovation. It demands mastery across regulatory navigation, clinical validation, quality management, and commercialization strategy. For many MedTech organizations, these challenges outpace internal resources or require niche expertise that is difficult to scale. Full-service MedTech consulting is a potential solution.  This integrated approach spans the entire product life cycle. Unlike traditional consultancies that focus on discrete phases, RQM+ offers comprehensive support from concept to commercialization. The result? Accelerated timelines, reduced risk, and stronger alignment with business goals. Here’s what full-service MedTech consulting can deliver for your organization. 1. Continuity From Concept Through Commercialization Fragmented service providers often create gaps, delays, misalignment, and require partnering with multiple service providers. This puts the onus on the MedTech organization to manage multiple suppliers to keep projects on track. Full-service consulting solves this by unifying critical functions—regulatory affairs, quality assurance, clinical trials, and market access—within a single, coordinated framework. Advantages of an integrated approach: Cross-functional teams that share project context and strategy Reduced handoff risk and faster execution across development phases Adaptive strategies that evolve with product maturity and market conditions At RQM+, for example, teams guide clients through FDA pre-submission, pivotal trials, CE mark readiness, and post-market surveillance—all within one streamlined ecosystem. 2. Accelerated Execution With Fewer Delays With aligned teams and overlapping timelines, full-service consultancies deliver faster results. Coordination is built-in, eliminating the friction that typically slows down device development. Key benefits include: Centralized project management that keeps milestones on track Simultaneous planning and execution of lab testing, clinical design, and regulatory strategy Early identification of risks and quick access to mitigation resources In practice, RQM+ clients have shortened approval cycles by integrating lab testing from Jordi Labs directly into regulatory submissions, enabling seamless biocompatibility assessments. 3. On-Demand Access to Specialized Expertise Development trajectories often shift—whether due to new materials, updated standards, or regulator feedback. A full-service firm offers flexible access to domain experts, without the delays of onboarding new vendors. When this flexibility matters: Needing toxicology input after a material change Scaling clinical trial resources mid-study Responding to an unexpected FDA request letter With RQM+, clients gain access to the largest team of MedTech regulatory and quality consultants globally, ready to flex across time zones and project scopes. 4. Improved Regulatory Readiness and Quality Integration Embedding quality and regulatory considerations from the outset reduces non-compliance risks and late-stage redesigns. Full-service firms ensure that development aligns with current global requirements—across the US, EU, and beyond. Benefits of built-in regulatory rigor: Seamless integration of design controls and verification into development Consistent, audit-ready documentation across functional areas Strategic interpretation of FDA, MDR, and IVDR guidance The outcome? Faster review cycles, fewer regulator queries, and stronger product dossiers. 5. Strategic Insight for MedTech Executives Beyond technical execution, full-service consulting brings strategic value. These partners offer a holistic perspective—connecting device design with market dynamics, competitive positioning, and reimbursement pathways. Why leadership teams benefit: More predictable development costs and resource planning Comprehensive risk assessments that inform go-to-market timing Market access and payer insights built into early-stage planning RQM+ operates not just as a vendor but as a strategic extension of the executive team—helping leaders accelerate value realization while navigating evolving market landscapes. Interested in MedTech Consulting? Full-service MedTech consulting isn’t just about efficiency—it’s about building smarter, more resilient product strategies from the ground up. Whether you're launching your first product or navigating the latest regulatory reforms, a partner like RQM+ offers the agility, depth, and cross-functional strength to move faster and safer. For MedTech executives, the gains are clear: fewer delays, reduced risk, and a faster route to clinical impact. RQM+ Flexible Partnering Solutions meet you where you are. Choose Outsourcing for full project or functional ownership, Consulting for targeted expertise and hands-on execution, or Staff Augmentation to fill skill and capacity gaps with vetted MedTech professionals. For the latter, you can start with a consultative conversation or use our Match with a Contractor form to get curated talent fast. Further Reading : Greenlit in Europe, Grounded in America: A Medtech Paradox #### What GMP Means in Pharma The acronym GMP refers to the good manufacturing practices promoted by the U.S. Food and Drug Administration (FDA) under the remit of the FD&C Act; which mandates strict levels of quality assurance at every stage of the pharmaceutical manufacturing chain. Although GMP principles are not exclusive to drug production and packaging, this article will focus specifically on GMP guidelines in the pharma industry. What Exactly is GMP? Good manufacturing practice is a critical system used to ensure that drugs and medical devices are produced according to the highest quality standards. Although the overarching framework of GMP is set up by the FDA, continuously adhering to the most stringent levels of quality control demands a robust set of internal protocols for ensuring that every link in the manufacturing chain is above reproach from a quality assurance perspective. Essentially, GMP is a pharmaceutical quality benchmark which is achieved by setting an extremely high bar for ongoing QA/QC. Understanding GMP Pharma Guidelines As most GMP principles are relatively open-ended, the onus is on the pharmaceutical manufacturer, processer, and/or packager to implement the necessary controls which are in-keeping with current good manufacturing practices (cGMP). Current indicates that the systems used should be reasonably up-to-date. So, while there is an element of interpretation and flexibility in cGMP guidelines, modern systems should be deployed in order for the QA process to be adequate. The FDA defines company GMP practices as a formal system of controls which help to prevent contamination, deviation, errors, failures, and mix-ups which will ensure that drug products meet internal quality standards: “This includes establishing strong quality management systems, obtaining quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories.” Consequences of GMP Non-Compliance GMP guidelines in the pharma industry are established to prevent contamination and errors which could be hazardous—or in the worst case fatal—for end users. Adhering to GMP guidelines also mitigates the risk of delivering ineffective products to consumers. As a result, non-compliance opens the door to litigation and regulatory action. The FDA considers any drug manufactured by a company not complying with cGMP standards to be adulterated, and though distribution is rarely halted to minimize disruption to established patient therapies, action may be taken cease manufacture where a drug is deemed unsafe. In other cases, such as where a product does not offer the marketed benefits, the FDA may order a recall and seize the drug on the rate occasion when a pharma company refuses to comply with that request. Fortunately, the FDA routinely publishes guidance documents for complying with GMP pharma regulations, to help new drug companies learn the basics of cGMP and how to reduce the risk of releasing a sub-par product to market. Following GMP Pharma Guidelines It is important to remember that cGMP protocols set the bar for a minimum level of pharmaceutical quality, and that many companies will have existing QA/QC practices which go above and beyond the regulatory requirements. But it is never worth running the risk of non-compliance. If you are involved in the pharmaceutical manufacturing chain and would like to ensure your test results are in line with cGMP guidelines, why not contact a member of the RQM+ Lab Services team today? Source: https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-manufacturing-practices-cgmps Further reading - Good Manufacturing Practice in the Medical Device Industry #### What Is a Contract Research Organization (CRO)? Launching a pharmaceutical, biotechnology, or medical device product demands more than innovation—it requires precise clinical trials management, strong data management practices, and full alignment with good clinical practice standards. Pharmaceutical companies face increasing complexity in clinical development, from patient recruitment and site selection to regulatory submissions and quality assurance. Contract research organizations (CROs) offer a wide range of research services that streamline the clinical trial process. By managing trial data, ensuring development clinical standards, and adapting to real world challenges, a contract research organization becomes an essential partner in drug development. With deep expertise in contract research, CROs help sponsors meet regulatory demands and accelerate time to market. Rather than building and maintaining in-house teams for every development function, sponsors—from startups to global manufacturers—can leverage CRO expertise to bring new products to market more efficiently, safely, and compliantly. The Role of CROs in the Product Development Lifecycle Contract research organizations operate at the intersection of science, regulation, and logistics. They support sponsors by delivering critical services across three main areas: Clinical Research: Including study design, protocol development, site selection, and clinical trial execution. Regulatory Affairs: Providing strategic guidance, authoring submissions, and managing communications with agencies such as the FDA, EMA, and Notified Bodies. Quality Systems: Developing or refining quality management systems (QMS), conducting audits, and ensuring adherence to standards such as ISO 13485, EU MDR/IVDR, and GCP. This breadth of services allows CROs to act not merely as vendors, but as integral partners in accelerating innovation while reducing operational burden and regulatory risk. Key Benefits of Partnering with a CRO Choosing to work with a contract research organization provides sponsors with numerous strategic advantages: Tailored Expertise: CROs bring deep domain knowledge across therapeutic areas and device classes. Their teams often include clinicians, statisticians, regulatory experts, and quality engineers with decades of experience. Scalability and Efficiency: With established global infrastructure, CROs can scale operations up or down based on project needs. This flexibility reduces the cost and complexity of building internal capabilities. Faster Time-to-Market: CROs streamline timelines through efficient trial execution, robust SOPs, and ready-to-go site networks—ultimately helping sponsors meet commercial milestones more quickly. Regulatory Insight: CROs monitor evolving regulations and proactively adapt study designs and evidence strategies to meet the latest requirements. Risk Mitigation: By handling trial oversight, monitoring, and safety reporting, CROs help ensure compliance and protect patient safety, which in turn supports regulatory success. These benefits are especially critical in MedTech, where new product development often involves iterative prototyping, evolving indications, and strict post-market obligations. What Makes a MedTech-Focused CRO Different? Medical device and diagnostics trials require a different mindset and skill set than pharmaceutical trials. Device studies often involve smaller cohorts, engineering iteration during development, and hybrid study designs that combine bench testing, usability evaluation, and clinical evidence generation. A contract research organization must therefore not only understand the science but also the specific design and regulatory pathways relevant to medical technology. This is where RQM+ stands apart. RQM+: Your Integrated MedTech CRO Partner At RQM+, we provide end-to-end CRO services designed specifically for the medical device, diagnostic, combination products, and digital therapeutic sectors. Our model goes beyond traditional service delivery—we function as a seamless commercialization platform that integrates regulatory, clinical, and laboratory expertise across the entire product lifecycle. From first-in-human feasibility studies to pivotal trials, from material characterization in the lab to full regulatory submissions and post-market surveillance, RQM+ offers one connected team with deep operational experience and regulatory foresight. Our clients benefit from: MedTech-Focused Clinical Trial Execution: RQM+ designs and manages early feasibility, pilot, pivotal, and post-market studies with a focus on patient safety, meaningful outcomes, and device-specific endpoints. Embedded Regulatory and Quality Strategy: We build compliance into product development from day one, ensuring alignment with FDA, EU MDR/IVDR, and ISO 13485 standards from design controls to post-market obligations. In-House Laboratories and Testing Capabilities: Our labs support device and diagnostic development with material characterization, biocompatibility testing, and bench studies that feed directly into clinical and regulatory planning. Proactive Evidence Planning: Our regulatory strategists include former FDA reviewers and notified body representatives who anticipate the evidence requirements for today’s (and tomorrow’s) regulatory environments. This integration enables faster iteration, clearer documentation, and fewer surprises during agency review. Why RQM+? Bringing a MedTech product to market is a marathon, not a sprint. It requires sustained effort across disciplines—each with its own challenges, risks, and timelines. At RQM+, we’ve built a CRO that is fully aligned with the unique demands of medical devices, combination products, diagnostics, and software-enabled products. Whether you’re a startup aiming to validate a new concept or an established manufacturer navigating a complex regulatory shift, we offer the infrastructure, insight, and integration to help you succeed. If you're looking for a contract research organization that brings more than just services—a true partner that can anticipate challenges, streamline processes, and accelerate your path to market—RQM+ is ready. Let’s build your roadmap from concept to commercialization. Contact RQM+ today to schedule a consultation with our clinical trials, lab, regulatory and quality, and reimbursement experts. Together, we’ll bring your innovation to life: safely, efficiently, and with confidence. #### What is Elemental Analysis Used For? Elemental analysis is a process in analytical chemistry in which a sample of material such as water, minerals and bodily fluid is analyzed to ascertain its elemental composition. Elemental analysis can be qualitative, determining which elements are present or quantitative, determining the levels of elements. This article will outline some of the key forms of elemental analysis and what they are used for. Scanning Electron Microscopy Elemental analysis can be used to provide surface elemental composition information for scanning electron microscopy (SEM) for areas as low as nanometers in diameter. An electron beam scans the sample and monitors reflected electrons from the sample surface. The impact of this electron beam creates X-rays which are representative of the elements present in the sample. This type of elemental analysis can also create elemental maps of the surface of a sample which can show which elements are present in small localized impurities or broad phases. Neutron Activation Analysis Neutron activation analysis is a highly sensitive and precise method for attaining needs of industries for trace elemental analysis. This sampling of elements is discrete, focusing specifically on the atomic nuclei of a sample. The elements form radioactive isotopes as the sample is bombarded with neutrons. This results in radioactive emissions and decay paths being determined which leads to the establishment of exact elemental concentrations. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) ICP-MS is an elemental analysis technology which can detect many of the periodic table of elements at milligram to nanogram levels per liter. This technique combines a highly sensitive mass spectrometric detector (percent level to parts per trillion (ppt) range) with an inductively coupled plasma source. It is employed in a range of industries such as geochemical analysis, metallurgy, environmental monitoring, pharmaceutical analysis, as well as in clinical research. Determining Carbon, Hydrogen, Nitrogen, Sulfur and Oxygen Content Elemental analysis can be used to determine the levels of many gases via combustion analysis. This method employs the instant and complete oxidation of samples via “flash combustion”, converting every organic and inorganic substance into a combustion product and the resulting combustion gases determine the concentration information. This method of elemental analysis is particularly useful for ascertaining the elemental composition and purity of unknown compounds as they generally establish the weight percentage of the element in a compound. This is particularly useful for chemical characterization in materials science, natural products and pharmaceutical products. X-ray Photoelectron Spectroscopy for Chemical Analysis XPS is a method of elemental analysis which is used for the surface of a sample employing a monochromatic X-ray beam. XPS uses a monochromatic X-ray beam to cause the emission of core electrons and the kinetic energy which is emitted helps to identify the elements present. This form of elemental analysis can be used to characterize particular functional groups related to a specific element. X-ray Fluorescence This elemental analysis technique employs photons from an X-ray tube which leads to inner shell electrons leaving the excitation volume of a tested sample. Fluorescent photons are then produced to balance the difference in energy between outer and inner shells and the fluorescent X-rays are characteristic of the atoms they originate from. This particular method of elemental analysis works well in applications of quality control. Elemental Analysis from RQM+ Lab Services At RQM+ Lab Services we can offer elemental analysis for a broad spectrum of inorganic components such as Uranium and Hydrogen. We are able to analyze even ultra-trace elements and both surface and bulk elemental composition. #### What is Polymer Material Performance Testing? Polymers are integral to medical devices, offering the trifecta of versatility, biocompatibility, and adaptability–provided they are up-to-standard. At RQM+ (and Jordi Labs), we’re intimately aware of the challenges of polymer material performance testing during medical device development, as well as the cost of getting it wrong. Such testing ensures that devices meet stringent safety standards and regulatory expectations. It's a process we genuinely value because it directly impacts patient safety, regulatory compliance, and ultimately, the successful approval and market entry of medical devices. Why Polymer Performance Testing Matters for Medical Devices Polymers have become indispensable across the gamut of medical applications—from catheters and stents to wearable health monitors and surgical implants. These materials offer unique advantages like flexibility, chemical inertness, and customizable mechanical properties. But we've also seen what can happen when polymer materials aren't rigorously tested. Failures can result in serious issues such as device recalls, harm to patients, and regulatory noncompliance, particularly with bodies like the FDA and EU MDR. Through material performance testing, we help manufacturers identify and mitigate potential risks such as polymer degradation, mechanical stress failures, or instability over time. By proactively addressing these concerns, we safeguard patient safety, ensure reliable device performance, and meet stringent regulatory requirements—all foundational elements of the work we do every day. Key Types of Polymer Performance Testing At RQM+, we handle a comprehensive array of polymer performance tests to thoroughly evaluate material properties and how they behave under real-world conditions: Mechanical Testing: We assess tensile strength, elongation, fatigue resistance, and compression strength. These tests show how materials react to physical stresses experienced in actual medical use, ensuring long-term durability and reliability. Thermal Analysis: Polymer performance can change significantly with temperature. Thermal analysis, including thermal degradation and stability, helps identify how polymers respond to heat during processes like sterilization, or exposure to human body temperatures over time. Chemical Resistance and Stability Testing: It's essential to confirm that polymer materials can withstand interactions with bodily fluids, sterilization chemicals, and pharmaceuticals without degrading. We perform these tests to ensure that no unforeseen chemical reactions compromise patient safety or device integrity. Biocompatibility Testing: Confirming that polymers are safe for patient contact is crucial. By following ISO 10993 standards, we ensure materials do not provoke harmful biological responses, supporting both regulatory compliance and patient safety. Accelerated Aging: Medical devices must perform reliably throughout their intended shelf life. Our accelerated aging tests simulate extended periods to confirm ongoing device safety and effectiveness. We don't just conduct these tests—we translate the complex results into actionable insights to support our clients' successful regulatory submissions. Navigating Regulatory Expectations: More Than Just Compliance The regulatory landscape for polymer materials has significantly evolved, especially with increased scrutiny from agencies like the FDA and EU MDR. Today, authorities expect detailed, comprehensive polymer testing data demonstrating proactive consideration of material safety and performance. We emphasize staying ahead of these evolving expectations by integrating proactive testing strategies into product development from the outset. Our team helps clients adopt rigorous, transparent testing programs aligned with current regulatory requirements. Doing this not only facilitates smoother regulatory approval but also avoids costly delays and enhances the marketability of medical devices. Addressing Common Challenges: How We Help We know that navigating polymer testing can be complex. Manufacturers often struggle with insufficient testing scopes, misunderstanding regulatory standards, or generating inadequate data, leading to regulatory setbacks. Our integrated team of regulatory experts, scientists, and clinical specialists addresses these exact challenges. We collaborate closely with our clients, helping them define the right testing protocols, correctly interpret regulations, and communicate results effectively to regulatory bodies. By leveraging our experience, we ensure our clients can confidently navigate the complexities of material testing from concept through to market approval. Looking Ahead Polymer material performance testing isn't just about meeting regulatory requirements—it's central to ensuring medical device safety and effectiveness. At RQM+, we remain committed to staying ahead of industry trends, and constantly adapting to evolving regulatory landscapes. Our goal is to provide clear, strategic guidance that supports innovation, compliance, and, most importantly, patient safety. Together, we're shaping the future of medical device development, ensuring safer and more reliable solutions for everyone. #### What is Polymer Molecular Weight? Polymer molecular weight (MW) is the molecular mass of a polymer chain. While small molecules of the same elemental composition all exhibit the same molecular weight, polymer chains exhibit different characteristics. These chains are compounded from multiple small molecules that can alter the mechanical behavior of the polymer and skew its molecular weight. This makes determining a consistent molecular weight for synthetic polymer chains almost impossible. As such, a bell curve distribution is used to determine polymer molecular weights and find an average value for synthetic polymer chains. Three distinct molecular weight averages are used to ascribe a numeric value for the molecular weight distribution of polymer chains: The number average molecular weight (Mn), which describes the lowest portion of molecular weight of the sample; The weight average molecular weight (Mw), which describes the average that is closest to the center of the bell curve; The Z average molecular weight (Mz), which describes the highest portion of molecular weight of the sample. The Importance of Polymer Molecular Weight The physiochemical properties of a polymer are entirely dependent upon the molecular weight and its distribution throughout the polymer chain. Consistency is critical for numerous manufacturers in sectors as varied as the pharmaceutical, biotech, litigation, and petroleum industries. The properties of commercial polymers also depend upon the molecular weight of the chains used in their construction. Products such as car parts and food packaging depend upon ductile materials that exhibit good plastic deformation to withstand rugged daily use. Polymeric materials are fundamentally varied. Those consisting of a low number of repeated units, thus low molecular weight, tend to exhibit soft or even fluidic properties with little mechanical strength. Conversely, larger chains with increased molecular weight display solid properties with vastly improved physical integrity over their shorter chain counterparts. These properties can determine the softening and melting points of a polymeric product, its solution and melt viscosity, and its elasticity. Determining Polymer Molecular Weight Molecular weight is determined by multiplying the mass of each subsequent repeating unit in the polymer chain, before adding the mass of either end group. This provides a range of values that are used to establish the molecular weight distribution of the material. The average molecular weight is the most common value of merit for manufacturers, but the low and high portion molecular weights are also important for understanding the entire distribution curve and establishing the broader characteristics of the polymer. The processing properties of polymeric materials are largely determined by their molecular weight distribution, with narrower distribution curves typically suggesting improved mechanical and processing properties compared to broader distributions. This is due to the plasticizing effects of the low portion molecular weight that softens the material, while the high portion disproportionately contributes to the melt viscosity. Molecular Weight Distribution with RQM+ Lab Services RQM+ Lab Services provides unparalleled expertise in the field of molecular weight analysis, using cutting-edge chromatographic techniques to determine polymer molecular weight distributions with outstanding degrees of accuracy. We use Gel Permeation Chromatography (GPC) to determine polymeric molecular weight distributions for a broad range of products. If you would like any more information about GPC technology or analyzing polymer molecular weight, please do not hesitate to contact us. #### What is the Benefit of Seeing the Brain? Defining and demonstrating clinical benefits of diagnostic imaging The prevalence of research into brain imaging modalities has solidified this practice into a relied-upon tool to provide information on a variety of neurological conditions. These devices are tools to not only see the structure of that once elusive yet fascinating part of the anatomy but to also guide treatments for nearly any neurological condition including epilepsy, stroke, cancer, and Parkinson’s disease to name a few. When it comes to assessing these imaging devices and determining regulatory and market acceptability, the fundamental question is “do the benefits outweigh the risks?” This question is captured in both GSPRs 1 and 8 (state GSPRs) and rely on the clinical evaluation report (CER) to demonstrate compliance. Intuitively, the answer is straightforward. Yes, of course we want a noninvasive method to see the brain. These pictures give us valuable insight into lesions, masses, and other structural anomalies under the surface. However, if you’ve ever submitted a CER to a notified body, you know that intuitive arguments don’t take you very far. We need to dig into the data, figure out a way to define benefits and risks, and provide evidence to justify the acceptability of the device. Balancing Benefits and Risks in Medical Imaging Devices Risk is generally the easier part to define, which is done by considering any potential harms to the patient. The most prevalent modern imaging techniques include MRI, CT- and PET-scans. While these methods are noninvasive, that doesn’t always equate to no risk. For example, some of these technologies emit radiation to both patient and user if precautions are not taken. Downstream cumulative effects of exposure can lead to very serious health risks, but are they acceptable considering the benefits of the technology? Describing benefits of the device should be done with the perspective of the state of the art in medicine. What are the alternatives to the device under evaluation? If this device was not on the market, what other options do clinicians have to view the brain? Consider a glioma patient whose healthcare provider uses diffusion tensor imaging (DTI) to determine tumor grade. Without DTI, the clinician’s other options may be a standard MRI or CT-scan. Communicating Value for Regulatory and Market Success Since the device does not provide a direct therapeutic effect, this is where manufacturers get stuck. They find it difficult to put a finger on the benefits of a diagnostic imaging device. Clinical benefit, by definition, is the positive impact of a device on the health of an individual, expressed in terms of any of the following: a meaningful, measurable positive impact on the health of an individual a meaningful, measurable, patient-relevant diagnostic outcome(s), a positive impact on patient management a positive impact on public health While DTI has no direct therapeutic benefit to the patient, we can highlight improvements in diagnostic outcomes and patient management that it provides. More accurate diagnosis (higher sensitivity and specificity) compared to traditional MRI and CT Less time to diagnosis compared to traditional MRI and CT Given the appropriate comparator, these outcomes can be evaluated against the state of the art to understand the value of DTI and the latest imaging technologies in neurological diagnoses. The true value of these images is in the accurate information they provide aiding clinicians in providing the appropriate care and treatment for their patients. As manufacturers recognize and communicate the ways that these devices can aid in patient management, they pave the way for regulatory success and true evolution in healthcare. Let's Make Neurology Happen If you're navigating the complex regulatory landscape for neurological imaging devices, you're not alone—and you don't have to go it alone. At RQM+, our experts specialize in helping manufacturers define clinical benefits, assess risks, and craft compelling CERs that meet regulatory expectations. Whether you're developing cutting-edge imaging technologies or refining existing devices, we’re here to support your journey to market success. Looking for more neurology device advice? Join us on June 26th for our RQM+ Live! panel discussion, "Electric Brains & Regulatory Pains: Accelerate Neurology Innovation, Slash Risk, & Win Approval." Gain practical insights from industry leaders and get your questions answered live. Contact us today to learn how we can help bring your neurological innovations to life—and don’t forget to register for the panel! #### What is Thermal Gravimetric Analysis? Thermogravimetric analysis, or thermal gravimetric analysis (TGA), is a method of determining the overall mass of a sample as a temperature-dependent property. Mass change as a function of temperature is a fundamental property of many materials as they degrade and lose volatile components. This phenomenon can provide rich detail about materials under test. By strategically subjecting a sample to a precise temperature program under strict atmospheric controls and simultaneously measuring changes in weight, thermal gravimetric analysis can provide vital data for a wide range of materials characterization objectives. Step-by-Step Principles and Procedure In simple terms, thermal gravimetric analysis provides a statistical readout of material mass as a function of temperature and time. This is carried out by heating samples in a chosen atmosphere on a highly accurate balance. Various temperature profiles can be programmed to suit different experiments, including parameters such as peak temperature, ramp rate and dwell times. Measuring the sample’s mass at regular intervals throughout this temperature profile yields a thermogravimetric curve where mass is plotted as a function of temperature or time. This characteristic curve is usually indicative of thermal decomposition; where elevated temperatures begin to break the sample down. Data Collection Through Thermal Gravimetric Analysis Determination of Content Thermal gravimetric analysis is routinely employed for content determination, providing accurate and actionable insights into sample composition. It is regularly employed to determine carbon and inorganic content. Properties of Reactivity & Corrosiveness Using thermal gravimetric analysis, researchers can prove the reactivity or corrosivity of sample materials when exposed to specific environments. This is particularly useful for metal alloys and catalysts. Changes in Size, Shape & Overall Mass Exposure to varying, pre-disposed temperatures and alternating thermal conditions can tell us if a composite might tend to shrink or expand, changing its size or shape, as well as, why this might occur. If, as researchers, we have a specific, targeted objective or use for a substance, the extent to which it is prone to possible changes in size, shape or scale may affect how the material is applied. Applications of Thermal Gravimetric Analysis The ability to accurately predict the durability, stability, and strength of a material carries wide-reaching connotations for cutting-edge technology, industry, and construction. Our chemists can understand the properties of a material which are significant to the goal of the specific application. If you would like more information about running thermogravimetric analysis with RQM+ Lab Services simply contact a member of the team today. Related Techniques Thermal Gravimetric Analysis #### What is Transmission Electron Microscopy? Transmission electron microscopy (TEM) is a form of microscopic analysis that transmits a high-energy beam of electrons through an ultrathin sample specimen. This provides imagery based on the transmission/attenuation of electrons, which is then magnified for direct observation and analysis on the micro- and nano-scales. It is a very high-resolution technique for mapping a samples size, shape, and elemental structure in the nanometer size range. Conventional microscopy is limited by the wavelength of photons used in visible light microscopes which are confined to imaging specimens of several hundred nanometers (nm) and upwards. Transmission electron microscopy allows direct observation of a sample’s structure and morphology at an atomic level, lower than a single nanometer. This blog post will explore transmission electron microscopy in more detail. The Working Principles of Transmission Electron Microscopy Transmission electron microscopy operates using three primary components: an electron source; a series of electromagnetic lenses; and a sensitive optical detector. The high-voltage electron gun directs a beam of accelerated electrons through a condenser aperture, which focuses the beam onto the ultra-thin sample. Transmitted electrons imprint an image based on the distinct optical characteristics of the sample onto a photosensitive screen. This screen then emits photons that are acquired and imaged using a high-resolution camera. These principles only operate effectively in low vacuum conditions otherwise gas molecules may interfere with the electron beam and cause inconsistencies in the generated micrograph. Applications of Transmission Electron Microscopy Transmission electron microscopy is ideal for characterizing materials on the sub-micron scale. It represents the most powerful magnification capacities and the highest possible resolution for microscopic imaging techniques, with a robust range of additional measuring parameters available for distinct applications. Transmission electron microscopy has been coupled with energy-dispersive X-ray spectroscopy (EDS) to accurately determine the elemental composition of samples down to the nanometer scale. It has also been combined with electron energy loss spectroscopy (EELS). This technique is most commonly used in materials research for biological and physical sciences, with good suitability for assessing the morphology of nanoparticles. It is also an established technique for identifying particulates and residue in pharmaceutical products. Transmission Electron Microscopy with RQM+ Lab Services RQM+ Lab Service provides expertise in the field of materials analysis for a broad range of industrial, commercial, and academic applications. We have been enabling researchers with cutting-edge analytical techniques and services since 1980, and we have since become a worldwide authority on how to detect, quantify, and eliminate particulate and residue for manufacturing chains. If you would like any more information about performing transmission electron microscopy with RQM+ Lab Services, please do not hesitate to contact us. #### Where can your CE mark take you next? By Chris A. Parr - Principal, CRO As a follow up to “Europe, the EU, and the EU Single Market: what are the implications of geopolitics for medical device manufacturers?” we will uncover market access outside the EU/EEA based on reliance and recognition. Regulatory reliance and recognition in countries outside of the European Union (EU) and European Economic Area (EEA) may form an important part of market access strategies. In this blog we will look at regulatory reliance and recognition based on the CE mark. We will review selected countries outside the EU/EEA in which manufacturers can leverage the CE mark as part of their regulatory strategies to achieve market access. What is Regulatory Reliance? Regulatory reliance, as defined in the "Draft Playbook for Medical Device Regulatory Reliance Programs" is the act whereby the regulatory authority in one jurisdiction takes into account and gives significant weight to assessments performed by another regulatory authority in reaching its own decision. The relying authority remains independent, responsible, and accountable for the decisions taken, even when it relies on the decisions, assessments, and information of others. What is Regulatory Recognition? Regulatory recognition (described in the same draft playbook mentioned above) is the acceptance of the regulatory decision of another regulator. Recognition should be based on evidence that the regulatory requirements of the reference regulatory authority are sufficient to meet the regulatory requirements of the relying authority. Recognition may be unilateral or mutual and may, in the latter case, be the subject of a mutual recognition agreement. The CE Mark (Conformité Européene) The CE mark for medical devices, while primarily intended for the EU/EEA, is also recognized or accepted in several countries outside the EU/EEA. Here is where your CE-marked medical device can potentially take you beyond the EU/EEA (map built with source material from Vemaps.com): Europe Albania Bosnia and Herzegovina Montenegro North Macedonia Serbia Northern Ireland Switzerland Turkey United Kingdom Asia Pacific (APAC) Australia Malaysia Singapore Middle East and Africa (MEA) Israel Saudi Arabia In the subsequent sections we will examine each of these countries in more detail (in alphabetical order). Albania (Shqipëria) Albania is located in Europe but is not part of the EU or EEA. It is aligning its medical device regulations with the MDR/IVDR and recognises the CE mark for market access. It recognises CE-marked medical devices and IVDs, meaning that if your device is CE-marked under the MDR (or IVDR), you do not need to undergo a full local conformity assessment. The CE mark is a prerequisite for registration and market access. The responsible authority is the National Agency for Medicines and Medical Devices (Agjencia Kombëtare e Barnave dhe Pajisjeve Mjekësore, AKBPM1) Australia In Australia, the Therapeutic Goods Administration (TGA2) allows the use of CE certificates issued under MDR/IVDR to support applications for device approval. This is part of a regulatory reliance strategy to streamline access to safe and effective medical devices. If a device has already been assessed by a notified body, then the manufacturer may be eligible for an abridged conformity assessment. This means submitting fewer documents, the TGA may reduce the depth of its own assessment, manufacturers may benefit from reduced assessment fees. Bosnia and Herzegovina (BiH) BiH is located in Europe but is not part of the EU or EEA. It is aligning its regulatory framework with the MDR/IVDR and recognises the CE mark for market access. However, local registration is required before a device can be placed on the market. The competent authority is the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (ALMBiH3). Registration is mandatory for all devices before they are placed on the market. Devices must be CE-marked under the MDR or IVDR for IVDs as applicable for the device’s classification. Israel Israel is located outside Europe and is not part of the EU or EEA. In Israel, the use of overseas market authorisation evidence plays a significant role in the medical device and IVD registration process, particularly under the Fast-Track Route managed by the Ministry of Health’s AMAR (Medical Devices Division4). Israel allows medical devices that have been approved in certain reference countries (including the EU) to be registered more quickly through the Fast-Track Route. Registrations via Fast-Track are valid for up to 5 years (3 years for implants). The Israeli approval cannot exceed the validity of the reference country’s authorisation. Malaysia In Malaysia, the CE mark is not automatically accepted for general market access, but it plays a significant role in simplifying the conformity assessment process, especially for medical devices and IVDs. Medical devices and IVDs approved by recognized foreign regulatory authorities (including CE-marked devices) can undergo a streamlined conformity assessment. Malaysia’s Medical Device Authority (MDA5) implemented Circular Letter No. 1/2025, which introduces a process called “verification”, where CE-marked devices can be registered more efficiently. Montenegro Montenegro is located in Europe but is not part of the EU or EEA. In Montenegro, overseas market authorisation evidence particularly from the EU and other recognized jurisdictions plays a supportive role in the medical device registration process. While Montenegro does not have a formal regulatory reliance pathway, it accepts and requires several documents that are typically issued by overseas authorities. A CE certificate under MDR or IVDR can be used to demonstrate compliance with international standards and support the local conformity assessment process with the Institut za lijekove i medicinska sredstva Crne Gore (CINMED6). Northern Ireland In Northern Ireland, the regulation of medical devices and IVDs is unique due to the Windsor Framework agreement which maintains alignment with EU laws for goods. Northern Ireland continues to follow the MDR and IVDR. This means that CE-marked devices under MDR/IVDR are required and accepted for placing products on the Northern Ireland market. The MHRA remains the competent authority for medical devices in Northern Ireland. However, EU Notified Bodies are responsible for conformity assessments under MDR/IVDR. North Macedonia North Macedonia is located in Europe but is not part of the EU or EEA. In North Macedonia, the regulation of medical devices is governed by the Agency for Medicines and Medical Devices (MALMED7) and is currently undergoing reforms to align more closely with EU standards as part of the country’s EU accession process. While North Macedonia does not have a formal regulatory reliance framework like Australia or Israel, it does accept and consider overseas market authorisation evidence, particularly from the EU and other regulatory authorities, as part of its device registration process. The CE certificate may be used to streamline the evaluation process, especially for devices already approved in the EU or other recognized jurisdictions. Saudi Arabia In Saudi Arabia, overseas market authorisation evidence plays a supportive but not standalone role in the medical device and IVD registration process. The regulatory authority is the Saudi Food and Drug Authority (SFDA8), and all devices must obtain Medical Device Marketing Authorization before being marketed. The CE certificate is typically part of the supportive information, but it does not replace the need for full documentation and conformity assessment. Serbia Serbia is located in Europe but is not part of the EU or EEA. In Serbia, the use of overseas market authorisation evidence is recognized and can support the registration of medical devices and IVDs, but it is not sufficient on its own. All devices must be registered with the Medicines and Medical Devices Agency of Serbia (ALIMS9) before being placed on the market. Serbia does not have a formal regulatory reliance pathway, but it does accept documentation from recognized jurisdictions (including the EU) to support the evaluation process. Serbia is aligning with EU standards as part of its EU accession process. The CE mark is accepted for medical devices if the product complies with Serbian technical regulations. Singapore In Singapore, the Health Sciences Authority (HSA10) allows the use of overseas market authorisation evidence to support the registration of medical devices and IVDs, particularly through its abridged evaluation routes. This is part of Singapore’s risk-based and internationally aligned regulatory framework. Singapore recognizes approvals from several reference regulatory agencies, including EU notified bodies. If a device has been CE marked, it may qualify for abridged evaluation in Singapore. Switzerland Switzerland is located in Europe but is not part of the EU or EEA. In Switzerland, the use of overseas market authorisation evidence, especially CE marking, has traditionally been central to medical device regulation. However, due to changes in the EU-Switzerland Mutual Recognition Agreement (MRA), the regulatory landscape has evolved, and Switzerland is now adapting its approach to include controlled acceptance of non-EU approvals, such as those from the US FDA. Switzerland primarily relies on CE marking but is now planning to open up to FDA-cleared devices through a controlled pathway. This marks a shift toward regulatory diversification, while still maintaining high safety and performance standards. Swissmedic11 is the national authority responsible for medical device regulation. Turkey (Türkiye) Turkey is partially located in Europe but is not part of the EU or EEA. In Turkey, overseas market authorisation evidence, especially CE marking, is central to the medical device regulatory framework due to the EU–Turkey Customs Union. Turkey has fully harmonized its medical device regulations with the MDR and IVDR. Medical devices and IVDs must bear the CE mark to be placed on the Turkish market. CE marking is accepted as proof of conformity with Turkish regulations, which are aligned with EU directives. The Turkish Medicines and Medical Devices Agency (TMMDA12) is the national authority responsible for device regulation. United Kingdom In the United Kingdom, the use of overseas market authorisation evidence for medical devices and IVDs is evolving under the post-Brexit regulatory framework. The UK now operates a distinct system for Great Britain (England, Scotland, and Wales) and Northern Ireland, with different rules for each. CE-marked medical devices and IVDs can be placed on the GB market until 30 June 2030. After that, UKCA marking becomes mandatory*, unless the proposed new international reliance routes are formally adopted. The Medicines and Healthcare products Regulatory Agency (MHRA13) is the national authority responsible for device regulation. * Will it, indeed? The MHRA have just announced that they will open further consultation on whether to recognise EU CE marked medical devices indefinitely due to the feedback received during the previous consultation on international reliance schemes. Whilst the MHRA's recent response to that previous consultation also indicates that they are going to move forward with a reliance scheme that accommodates 'approvals' from comparable regulator countries (Australia, Canada and the USA)14. Summary While the CE mark is primarily for the EU and EEA, many countries outside the EU/EEA recognize or rely on the CE mark to streamline their own regulatory processes. Several non-EU/EEA countries accept or rely on CE marking to varying degrees and for some it is mandatory. This reliance and recognition can be unilateral (one-way acceptance) or mutual (based on formal agreements) such as mutual recognition agreements. Manufacturers who make use of the CE mark in this way also need to be aware of any national legislation in those countries. While the CE mark may open the door, national legislation may cover things like language requirements, unique device identification (UDI), and postmarket surveillance. Related next steps If you’re having difficulty navigating the EU regulatory landscape and struggling to comply with horizontal EU regulations, our experts specialise in helping manufacturers develop comprehensive regulatory strategies designed to ensure that medical devices and IVDs comply with all applicable EU legislation. Contact us to discuss how we can support your efforts and stay tuned for more updates related to the European Medical Device landscape in our upcoming blog posts. https://akbpm.gov.al/ https://www.tga.gov.au/ https://almbih.gov.ba/en/agencija-za-lijekove-i-medicinska-sredstva-bosne-i-hercegovine-eng/ Medical Device Division, Ministry of Health https://www.mda.gov.my/ https://cinmed.me/en/ https://malmed.gov.mk/ https://www.sfda.gov.sa/en https://www.alims.gov.rs/english/ https://www.hsa.gov.sg/ https://www.swissmedic.ch/swissmedic/de/home.html https://www.titck.gov.tr/ https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency https://www.gov.uk/government/consultations/consultation-on-medical-devices-regulations-routes-to-market-and-in-vitro-diagnostic-devices/outcome/response-to-international-reliance-ukca-marking-and-in-vitro-diagnostic-devices-consultation-proposal #### Why Agile Staffing Is Essential for Regulatory-Heavy MedTech Projects Bringing a high-risk medical device or diagnostic to market demands more than just innovation—it requires precise execution across complex regulatory and quality systems. Whether preparing a CE mark technical file under the EU MDR, submitting a 510(k) application to the FDA, or remediating legacy products, regulatory-heavy MedTech projects generate unpredictable and intensive workloads. In such high-stakes scenarios, internal teams are often stretched to capacity. That’s why agile staffing—the strategic deployment of flexible, specialized personnel—has emerged as a mission-critical tool for MedTech organizations. For regulatory leaders and MedTech executives alike, agility is not a luxury—it’s a competitive edge. The Challenge: Regulatory Demands Are Unpredictable and Relentless MedTech regulatory and quality teams routinely face surges in workload due to: Unanticipated regulator feedback requiring new data or analyses Compressed timelines for product launches or regulatory remediation Simultaneous global submissions and compliance updates Traditional staffing models can’t keep pace. Hiring is slow, training is time-consuming, and even seasoned teams can be overrun by submission backlogs or audit prep requirements. What Is Agile Staffing in MedTech? Agile staffing refers to the ability to scale regulatory, clinical, and quality operations quickly by deploying pre-vetted experts for short- or mid-term assignments. These professionals integrate seamlessly into internal teams and help deliver time-sensitive outcomes with minimal onboarding and guidance. Agile staffing resources can include: Regulatory affairs specialists with FDA, EMA, or notified body experience Quality system engineers and auditors for ISO 13485 and MDR readiness Clinical research associates (CRAs) and trial managers for site expansion or data cleaning Risk management and biocompatibility experts for technical documentation Unlike traditional outsourcing, agile staffing is dynamic, strategic, and responsive to immediate project needs. The Advantages of Agile Staffing for Regulatory-Heavy Projects 1. Hit Regulatory Deadlines Without Compromising Quality In regulated industries, speed is meaningless without accuracy. Agile staffing helps teams respond to tight deadlines and evolving requirements while maintaining high documentation standards. With agile staffing, teams can: Complete or revise regulatory submissions under pressure Tackle Q-sub meetings or Notified Body feedback with precision Scale documentation efforts to match clinical, labeling, or cybersecurity updates RQM+ routinely delivers qualified experts within days—keeping your team productive and projects on track. We also increase the likelihood of regulatory acceptance for submissions. There are many consultants who could complete your submission quickly, but speed of completion is ultimately worthless if that submission ends in rejection.  2. Fill Expertise Gaps Quickly Certain regulatory requirements—like IVDR performance evaluations or software risk classifications—demand niche expertise. Agile staffing connects you with professionals who specialize in these domains. Examples of high-impact skills: Toxicologists and analytical chemists for biocompatibility assessments Software and cybersecurity experts for SaMD and digital health products Regulatory strategists with cross-border experience (EU MDR, UKCA, MDSAP) By eliminating the learning curve, these experts reduce risk and accelerate readiness. 3. Scale Responsively With Project Demand As product portfolios grow or timelines compress, teams must expand rapidly—then contract without excess overhead. Agile staffing offers that operational elasticity. This means you can: Ramp up support during audits, inspections, or trial launches Reduce team size post-submission or post-market transition Maintain a lean core team without risking project delays This flexibility allows for smarter budgeting and more adaptive planning. 4. Maintain Momentum During Internal Transitions Turnover, parental leave, or rapid growth can all leave critical gaps. Agile staffing helps maintain continuity without sacrificing project knowledge or momentum. Key use cases include: Interim coverage for senior regulatory roles Backfilling QA/RA talent during hiring freezes Bridging support for new product teams With RQM+, you gain immediate access to experienced professionals who align with your systems, tools, and expectations. 5. Outpace Competitors With Faster Execution In MedTech, every delay can cost market share or funding. Agile staffing supports strategic speed—allowing you to file faster, respond sooner, and scale smarter. Tangible business benefits: Faster time-to-market for critical devices More responsive engagement with regulators Greater confidence among partners and investors Agility is not just operational—it’s a marker of leadership in today’s competitive MedTech environment. RQM+ Agile Staffing in Action RQM+ offers a deep bench of domain-specific professionals ready to support clients in regulatory, quality, clinical, and lab operations. Their agile staffing services include: Rapid deployment of pre-screened talent tailored to your project Seamless integration with internal teams and systems Strategic oversight to ensure alignment with broader program goals Whether you need a single submission specialist or an entire remediation team, RQM+ scales to meet the needs of your MedTech project, on your terms. Closing Thoughts The pace and complexity of MedTech regulation demand more than internal capacity can often deliver. Agile staffing fills that gap—not reactively, but strategically. For regulatory-heavy projects, it’s the smartest way to scale without compromise. By partnering with an agile provider like RQM+, MedTech companies gain the flexibility, speed, and precision needed to meet regulatory expectations, protect timelines, and succeed in a fast-moving market. Exploring MedTech Consulting? Full-service support isn’t just about doing more, it’s about designing stronger, more resilient product strategies from day one. Whether you’re bringing a first device to market or responding to shifting regulations, a partner like RQM+ brings the agility, depth, and cross-functional horsepower to accelerate progress with confidence. For MedTech leaders, the upside is clear: fewer delays, lower risk, and a faster path to clinical impact. RQM+ Flexible Partnering Solutions meet you where you are. Choose Outsourcing for end-to-end project or functional ownership, Consulting for targeted expertise and hands-on execution, or Staff Augmentation to add vetted MedTech talent and capacity. Prefer to start quickly? Begin with a consultative conversation or use our Match with a Contractor form for curated candidates fast. #### Why You Should Verify Your Supplier's MedTech Materials In the MedTech sector, the biocompatibility of materials is critical for patient safety and product efficacy. Every material needs to be tested, with suppliers often providing quality and biocompatibility assurances. As convenient as it is to take them at their word, the stakes are too high to trust your suppliers. MedTech companies are ultimately responsible for their products and any failings will likely result in severe legal and regulatory problems for the company — not the supplier.  In this article, we explore what MedTech businesses can do to gain greater control and understanding over supplier-provided materials. Let’s start by first unpacking the risks of relying on supplier data.  Can You Trust Supplier-Provided Data? Ensuring the biocompatibility of materials requires clear sightlines over testing. This is the only way to guarantee all materials comply with key regulatory and quality checkpoints. When it comes to supplier-provided biocompatibility data, however, tests are often performed in a black box.  In other words: you know what materials are being tested and you are handed the test results. But, as you have no view of the procedure, you have no idea how rigorous and accurate the testing is. This black box scenario leaves significant room for error and misinterpretation.  The supplier, for instance, might declare a material as medical grade, yet the definition of 'medical grade' is far from consistent across the industry. The supplier's testing methods may lack the thoroughness and expertise required to uncover potential contaminants, degradation products, or individual chemical components that jeopardize patient safety. Supplier testing processes may not align with evolving regulatory requirements and industry standards, leading to inadequate or incomplete biocompatibility tests. This can delay the time-to-market for products. Fortunately, a proactive approach can minimize these risks and guarantee the biocompatibility of materials.  Mastering Knowledge Over Product Materials Biocompatibility testing should take place both before and after MedTech materials are provided by new suppliers. The more meticulous and proactive your approach, the smoother your path to regulatory compliance. To gain full knowledge of supplier materials, follow these three steps: Perform Preliminary Tests Before Engaging Suppliers Early-stage chemical profiling reveals the inherent properties of materials, potentially uncovering attributes that could either be beneficial or detrimental in the medical device's real-world application. This should be conducted long before a supplier is engaged. Conduct Verification Testing After Supplier Engagement Once materials are provided, you must validate the supplier’s biocompatibility claims. This involves unboxing the 'black box' of supplier-provided data and engaging in rigorous testing to ascertain the true biocompatibility of the materials. This verification phase also accounts for any new variables that the manufacturing process might introduce, which could affect biocompatibility. Implement Continuous Quality Control Testing Quality control testing is a continuous commitment to ensuring that materials uphold the required standards and specifications over time. By maintaining a vigilant eye, you also ensure materials remain compliant with evolving regulatory standards. The meticulous approach of early and thorough verification of materials' biocompatibility pays dividends in the long run. It paves the way for a smoother regulatory approval process and significantly mitigates the risks associated with supplier-provided data.  A key risk is that suppliers may change their materials without informing you. These changes might be identified too late in the quality control process. This brings us to our next point. The Necessity of Robust Quality Agreements Establishing robust quality agreements with suppliers is critical for successful and transparent collaboration. These agreements define the standards, specifications, and responsibilities that govern the supplier–manufacturer relationship.  A robust quality agreement sets clear specifications for the materials, stipulating the testing and quality control measures that must be adhered to. It lays down the terms for quality assurance, inspections, and audits, ensuring a coherent understanding between all parties.  A well-structured quality agreement ensures that you are notified about any changes to the materials, processes, or sub-suppliers. This is crucial, as any alterations can have significant implications on the biocompatibility and overall safety of medical devices. Building a Resilient Supply Chain for MedTech Materials To secure continual access to quality materials, you need a network of reliable alternative suppliers. After all, recent global supply chain vulnerabilities such as those caused by the COVID-19 pandemic have been extremely disruptive for the MedTech industry. Those relying on a handful of suppliers found their product line impacted by stock-outs and delays. To avoid these situations, MedTech companies must find alternative material sources.  This is difficult news for many, as focusing on a single material source for regulatory approval saves time and money. Not to mention the work that goes into establishing new supplier relationships and performing additional material testing.  So, what can your business do to balance supply chain concerns with the need to quickly get your product to market? One strategy is to rely on a single source of materials for regulatory approval. Once approval is secured, you can focus on finding alternate suppliers and protecting your supply chain. Here, comparative studies, side-by-side material testing, and statistical analysis can help simplify the qualification process — potentially reducing the need for extensive biological testing. Either way, partnering with alternate suppliers is a crucial long-term strategy for building resilience and guaranteeing a continuous supply of quality materials. How RQM+ Can Help Verify Your Suppliers and Materials In MedTech, the only materials you can trust are the ones that you’ve verified yourself. Adopting a verification-centric approach requires performing precise chemical characterization and biocompatibility testing. You also need to keep pace with shifting standards and regulatory requirements. This is where RQM+ can help. As a full-service CRO, RQM+ provides comprehensive testing, analysis, and validation services to support regulatory compliance. Our expert Lab Services team can help you vet your suppliers and develop long-term strategies to safeguard the quality of your materials. Speak with our experts and ensure that you’re using the safest and most efficient materials for the job. Contact our team now to find out how we can support your material verification process.  Further Reading: Contaminant Analysis: How to Interpret Particulate Matter #### Why You Still Need Medical Writers in the Age of AI The rapid rise of artificial intelligence (AI) and large language models, such as GPT-4, has transformed how content is created across industries, including medical and regulatory writing. Many MedTech companies now wonder whether AI tools can replace human medical writers for developing Clinical Evaluation Reports (CERs), regulatory submissions, technical documentation, and other documents. While AI offers undeniable efficiencies, there are crucial reasons why expert medical writers remain indispensable.  At RQM+, our AI philosophy is driven by finding ways that AI can empower humans to be more efficient, but not to replace them. This evolution represents a shift toward human-AI collaboration rather than substitution. What Do Medical Writers Do in MedTech? Medical writers in MedTech occupy a vital space between science, regulation, and communication. They craft and organize complex technical documents that communicate scientific evidence, safety, and performance in a way that meets regulatory expectations. Their work includes: Clinical Trial Protocols and Reports. Clinical Evaluation Reports (CERs) and Post-Market Clinical Follow-up (PMCF) documentation. Regulatory submissions such as FDA 510(k)s, De Novos, PMAs, and EU MDR Technical Documentation. Risk-benefit analyses, scientific publications, and investigator brochures. Medical writers ensure documents are clear, accurate, and compliant with regulations and guidances such as the EU MDR, MDCG guidance, or FDA guidance. They collaborate with cross-functional teams—engineers, clinicians, statisticians, and regulatory specialists—to interpret complex data and craft a logical, evidence-based narrative. Their expertise lies not just in writing, but in scientific interpretation, regulatory alignment, and narrative coherence—areas where automation struggles. How AI Is Changing the Writing Process AI-driven writing tools have introduced real efficiencies. Generative AI can summarize literature, draft background sections, or refine grammar and phrasing. These tools help writers focus on higher-value tasks, such as analysis, interpretation, and strategy. However, AI’s capabilities have limits. Large language models draw from vast datasets, but they lack contextual understanding of a specific medical device or regulatory framework. They can produce outdated or inaccurate information, or even fabricate plausible but false content (“hallucinations”). In medical and regulatory writing, where precision, traceability, and compliance are core, such errors are unacceptable. AI also cannot evaluate confidential manufacturer data or weigh subtle regulatory nuances, both of which are critical for compliant submissions. Regulatory Requirements and the Need for Human Accountability Regulatory authorities and scientific publishers consistently emphasize human accountability. The International Committee of Medical Journal Editors (ICMJE) and major medical journals explicitly state that AI tools cannot take authorship, a human must accept responsibility for the content’s integrity. In regulatory contexts, qualified professionals must sign reports such as CERs or PMCF evaluations, attesting to their accuracy. Confidentiality and data protection also remain central concerns. Public AI models pose risks when used with proprietary or sensitive data. Medical writers manage this by ensuring secure data handling and full compliance with data privacy standards. They verify every citation, cross-check every claim, and tailor the message to regulatory expectations, a process requiring discernment that no AI can yet replicate. AI as an Augmentation Tool, Not a Replacement The most effective strategy is not replacing medical writers, but augmenting them. AI can handle structured, repetitive, or linguistic tasks, such as creating initial drafts when authors face writers’ block, summarizing standard sections, or flagging inconsistencies, while human writers provide the oversight, validation, and strategic interpretation. Using AI-assisted workflows writers can exemplify this model: automating low-level authoring tasks to improve consistency and free writers for higher-order analysis. Human writers contribute the critical thinking that ensures: Regulatory criteria are fully addressed. Evidence is interpreted correctly and ethically. The overall document narrative remains coherent and persuasive. AI can generate content, but it cannot judge whether an argument aligns with EU MDR or FDA standards. Only an experienced writer can. Pitfalls of Relying Solely on AI Several risks accompany an AI-only approach: Accuracy and truthfulness: AI systems may invent citations, misinterpret data, or fabricate statistics. One false statement could invalidate a regulatory submission or compromise patient safety. Nuance and tone: Regulatory documents require precise language. The difference between “may improve” and “is proven to improve” can determine compliance. AI lacks this contextual awareness. Up-to-date knowledge: Regulations evolve rapidly. While human writers track the latest EU MDR and FDA guidances and best practices, AI models operate on static training data. Ethical and legal accountability: AI cannot sign off on legal attestations, disclose its own use, or assume responsibility for errors. Human oversight is indispensable for ensuring ethical compliance. As the American Medical Writers Association (AMWA) notes, “chatbot output currently carries the risk of including biases, distortions, irrelevancies, misrepresentations, and plagiarism”. The World Association of Medical Writers has subsequently issued new recommendations, including: “chatbots cannot be authors”. Removing humans from the process thus risks both compliance failures and reputational harm. The Value of Human Expertise and Insight Human medical writers bring more than writing skill,they bring judgment, and strategic foresight. Many have clinical or scientific backgrounds, enabling them to: Interpret complex data and extract clinically meaningful insights. Craft cohesive narratives that preempt regulator concerns. Collaborate across departments to gather inputs and resolve inconsistencies. Ensure that every claim, table, and conclusion aligns with regulatory expectations. Complex documentation is inherently iterative and collaborative. It involves human negotiation, prioritization, and decision-making, dimensions that AI cannot reproduce. An apt analogy: AI is like an autopilot. It can handle certain aspects of flight efficiently, but a human pilot must manage takeoff, landing, and any turbulence. Likewise, AI can draft or format content, but human medical writers must steer the document to regulatory approval. Closing Thoughts AI is transforming medical and regulatory writing, but not by replacing humans. Companies like RQM+ demonstrate how AI-driven processes can enhance efficiency without sacrificing quality. The human writer’s role is evolving, from content producer to strategic editor, quality gatekeeper, and regulatory storyteller. Ultimately, regulators, investors, and patients place their trust in human accountability. AI can augment intelligence, but it cannot substitute it. The future of medical writing is human-guided automation, where skilled writers harness AI to deliver faster, more accurate, and more consistent documentation, while ensuring that every word stands up to scientific and regulatory scrutiny. References Brave New World: Authorship and AI in Medical Writing. American Medical Writers Association. 2023. https://blog.amwa.org/brave-new-world-authorship-and-ai-in-medical-writing. #### Wires to AI: The Regulatory Landscape of Neurological Devices Over the past few decades, the field of neurological devices has seen disruptive innovation, fueled by advances across the broader medical device industry. In response, FDA has continually adapted its review processes – both in practice and organizational structure – to keep pace with this evolution. The goal remains consistent: to ensure the safety, effectiveness, and clinical benefit of devices designed for neurological care. From traditional implants to cutting-edge, software-driven platforms, what does the neurological device landscape look like today – and how has the regulation of these devices evolved? The Modern Neurological Device Landscape Neurological devices encompass a wide range of technologies intended to detect, diagnose, treat, or support disorders of the central and peripheral nervous systems. These conditions span categories such as neurodegenerative diseases, neuromuscular disorders, and conditions affecting the brain, spine, and peripheral nerves – often in conjunction with other physiological systems. Examples of neurological devices include neurostimulation systems, neuroimaging tools, neurosurgical and neurointerventional technologies, and diagnostic platforms. Over time, there has been a notable shift from traditional, hardware-based implants to hybrid devices that integrate complex software components. Innovations in artificial intelligence and machine learning are now frequently embedded in device design, bringing new challenges and opportunities in areas such as cybersecurity, human factors, and real-time performance monitoring. How FDA Has Adapted In the early days of neurological device reviews, FDA regulatory oversight fell under divisions that were not solely specialized in neurology. Historically, these devices were reviewed within the Division of General Restorative Devices – primarily aligned with orthopedic technologies. While sufficient at the time, this structure limited the FDA’s ability to address the unique risks and complexities of neurological technologies, particularly as they became more software-driven and connected. Recognizing these limitations, the FDA gradually restructured its oversight. Here's a quick look at how regulatory oversight for neurological devices at the FDA has shifted over time – note that these dates are based on information found in FDA’s publicly available clearance & approval databases, and therefore they are approximate: Pre-2008: Division of General Restorative Devices 2008–2010: Division of General, Restorative and Neurological Devices 2010–2014: Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices 2014–2019: Division of Neurological and Physical Medicine Devices 2019–Present: Office of Neurological and Physical Medicine Devices (OHT 5), under the Office of Product Evaluation and Quality (OPEQ) A major turning point came in 2014, when neurological devices gained their own dedicated review division, allowing for more focused, consistent, and clinically informed evaluations of device safety and effectiveness. That structure was solidified in 2019 with FDA's Total Product Life Cycle (TPLC) reorganization, resulting in today’s Office of Health Technology 5 (OHT 5): Office of Neurological and Physical Medicine Devices. OHT 5 is organized into two Divisions of Health Technology (DHTs): DHT 5A (Neurosurgical, Neurointerventional and Neurodiagnostic) and DHT 5B (Neuromodulation and Rehabilitation Devices). Each of these DHTs is further divided into specialized sub-teams, each overseen by an Assistant Director. Like other OHTs, OHT 5 integrates both pre-market and post-market review, to ensure continuity and informed oversight across the product lifecycle. As neurological devices have grown more advanced with features like AI, machine learning, digital health tools, wearables, and nanotechnology, OHT 5 has had to stay ahead. Reviewers now work closely with the FDA’s Digital Health Center of Excellence and engage manufacturers early through Q-submissions and interactive reviews. OHT 5 has also taken a leading role in assessing emerging technologies such as brain-computer interfaces (BCIs), adaptive neurostimulation, and other therapies that blend hardware, software, and real-time data. FDA Pathways for Neurological Devices Neurological devices span a wide spectrum of FDA classifications (Class I through III) with most currently regulated under 21 CFR Part 882. However, due to the complexity of these technologies, some devices also fall under other FDA review panels such as orthopedics, ENT, or ophthalmology, and may be regulated under other sections of 21 CFR. Depending on the device’s risk profile and novelty, regulatory submissions may follow the 510(k), De Novo, or Premarket Approval (PMA) pathways. A rapidly growing area of interest is BCI systems. While no complete BCI system has yet received full FDA approval, several are in clinical trials or taking a stepwise regulatory approach – seeking clearance for individual components (e.g., brain mapping tools) while continuing broader system development. FDA’s 2021 guidance, Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-Clinical Testing and Clinical Considerations, outlines key considerations for design, risk management, and both non-clinical and clinical studies. To further support progress in this space, FDA joined a collaborative community launched by Mass General Brigham in 2024, focused on advancing the safety, effectiveness, and accessibility of BCI technologies. Participating organizations include Synchron, Precision Neuroscience, Blackrock Neurotech, Neuralink, and the BCI Society. This cross-sector effort reflects the growing importance of public-private collaboration in addressing the unique regulatory and technical challenges of next-generation neurotechnology. Neuroscience, Blackrock Neurotech, Neuralink, and the BCI Society. This cross-sector effort reflects the growing importance of public-private collaboration in addressing the unique regulatory and technical challenges of next-generation neurotechnology. Compliance Strategy and the Role of Subject Matter Experts Bringing a neurological device to market requires more than innovation – it takes a well-planned, adaptive compliance strategy. FDA reviewers expect: Clear evidence of safety, effectiveness, and usability Robust quality systems and a total product life cycle approach Alignment with current standards and guidance for non-clinical testing, such as software validation, cybersecurity, labeling, biocompatibility, and electrical safety Given this complexity, engaging subject matter experts (SMEs) early can be critical. Experienced regulatory consultants help interpret FDA feedback, shape submission strategies, and anticipate potential challenges. Specialized regulatory knowledge in areas like software as a medical device (SaMD), AI/ML, and clinical trial design can streamline the path to clearance or approval. RQM+’s Perspective As neurological devices become more advanced and software-driven, FDA has evolved to provide more specialized, life cycle-focused oversight. This has opened the door for faster, safer innovation in neurology. Our team has supported a wide range of manufacturers spanning early to mature stages on neurological devices ranging from implantables to AI-enabled platforms. We help companies navigate every phase of development – from regulatory strategy and FDA submissions to clinical trials, quality systems, laboratory services, reimbursement, and market access. Companies that plan early, understand the regulatory landscape, and work with the right experts are best positioned to bring safe, effective, and transformative neurological devices to patients Developing neurological devices in today’s complex regulatory environment requires more than technical excellence—it takes the right partner with deep FDA expertise and a proven track record. At RQM+, we specialize in helping MedTech companies accelerate progress while ensuring safety, compliance, and clinical impact. Let's Make MedTech Happen. Contact us today to speak with a neurological device expert. For more on a similar topic - Transhumanism – Science from Fiction: Part I – Bionic Body Parts and AI/ML-Enabled Medical Devices: Recognition & Reliance in the UK ### Pages #### About Us As The MedTech CRO, we’re your strategic partner in mutual success. Our experienced team uncovers the unknowns, guiding you through the nuances of regulatory compliance and market access. We’re your single stop for regulatory and quality services, lab expertise, clinical trial management and execution, and reimbursement solutions to provide full life cycle support for your MedTech products.  With expertise in medical devices, diagnostics, software-enabled products, and combination products, plus leading-edge technology and a people-centric approach, we ensure your innovations reach patients — faster, safer, better.  Explore Our Expertise Our MedTech Solutions Our portfolio of MedTech solutions span the entire product life cycle to accelerate your success:  Our Core Priorities Addresses and Phone Numbers United States HQ 5000 Centregreen Way,Suite 100Cary, NC 27513United States (U.S.) +1 877 652 0830 EuropeHQ 3rd Floor, 1 Ashley RoadAltrincham, Cheshire, WA14 2DTUnited Kingdom (U.K.) +44 115 921 6200 Switzerland Office Grosspeter TowerGrosspeteranlage 294052 BaselSwitzerland +41 61 511 4930 United States Lab Jordi Labs, an RQM+ Company 200 Gilbert St.Mansfield, MA 02048United States (U.S.) +1 833 888-0224 Germany  Frankfurt Office Eschersheimer Landstraße 1460322 Frankfurt/MainGermany +49 23 82 987-44-0 Germany  AhlenOffice Von-Geismar-Straße 259229 AhlenGermany The Evolution of RQM+ #### Blog Discover valuable insights and industry updates from our team of MedTech experts. Use the filters to explore content by topic, type, and region.  #### Candidate Privacy Statement Privacy Policy Client Privacy Notice Candidate Privacy Notice RQM+ is committed to processing your data securely and transparently. This privacy notice sets out the types of data that we collect and hold on you as a current or previous candidate for job opportunities with RQM+. It also sets out how we use that information, how long we keep it for and other relevant information about your data. RQM+ is aware of its obligations to residents and citizens of the EU under the General Data Protection Regulation (GDPR), of the UK under the Data Protection Act (UKDPA), of the USA under a variety of legislation and acts that include data protection requirements - specifically including the California Consumer Privacy Act (CCPA), of Switzerland under the Data Protection Act (DPA) and the Data Protection Ordinance (DPO), and the data protection requirements of residents and citizens of other countries. This privacy notice complies with the requirements of GDPR, UKDPA, CCPA, DPA and DPO and is applicable globally but may be supplemented by additional information on our privacy practices that may be provided as required by applicable laws and regulations via notices provided at the time of data collection. Together, these are referred to as “Data Protection Legislation”. This notice applies to individuals who are or have been job applicants. That is: Individuals who directly apply or respond to a job advertisement placed by RQM+ in the media including but not limited to LinkedIn, Job Board, local media. Individuals who apply directly or respond to a job advertisement placed by an Agency hired by RQM+ to search for candidates. Individuals who submit resumes/CVs to platforms such but not limited to Monster, CV Library, Career Builder, Total Jobs etc which RQM+ have legally obtained from such platforms. Individuals who have speculatively or voluntarily provided their resume/CV to RQM+. DATA CONTROLLER DETAILS RQM+ is a data controller, meaning that it determines the processes to be used when using your personal data. RQM+ has appointed Data Protection Officers who are responsible for ensuring your data is stored and processed in accordance with this privacy notice. Data Protection Officers can be contacted at dpo@rqmplus.com.  DATA PROTECTION PRINCIPLES In relation to your personal data, we will: process it fairly, lawfully and in a clear, transparent way collect your data only for reasons that we find proper for the course of your potential employment in ways that have been explained to you only use it in the way that we have told you about ensure it is correct and up to date keep your data for only as long as we need it process it in a way that ensures it will not be used for anything that you are not aware of or have consented to (as appropriate), lost or destroyed. TYPES OF DATA WE PROCESS We may hold many types of data about you depending on the length of our dialogues together regarding job opportunities: your personal details including your name, address, date of birth, email address, phone numbers your photograph gender marital status information included on your resume/CV/application including qualifications, references, education history and employment history information about your current level of remuneration, including benefit entitlements and your future expectations information about selection decisions for your application including shortlisting, interview notes, personality profiles and other selection activity performance data documentation relating to your right to work in the countries you are being considered to work in non-disclosure agreement HOW WE COLLECT YOUR DATA We collect data about you in a variety of ways including the information you would normally include in a CV or a job application cover letter, from your LinkedIn and/or job board profile or notes made by our recruiting officers during a recruitment interview and other selection activities. Further information will be collected directly from you when you complete forms at the start of your employment, for example, your bank and next of kin details. Other details may be collected directly from you in the form of official documentation such as your driving licence, passport, or other right to work evidence. In some cases, we will collect data about you from third parties, such as employment or recruitment agencies, former employers when gathering references, credit reference agencies or background checks where appropriate. Personal data is kept in electronic recruitment files and/or within RQM+ CRM, Applicant Tracking and IT systems. WHY WE PROCESS YOUR DATA The laws on data protection allows us to process your data. Data Protection Legislation allows us to process your data for certain reasons only: where we have your consent to do so in order to perform the employment contract that we are party to in order to carry out legally required duties in order for us to carry out our legitimate interests to protect your interests and where something is done in the public interest All of the processing carried out by us falls into one of the permitted reasons. Generally, we will rely on the first four reasons set out above to process your data as a candidate. We need to process data to take steps at your request prior to entering into a contract with you. We may also need to process your data to enter into a contract with you. We need to collect your data to ensure we are complying with legal requirements such as: carrying out checks in relation to your right to work in the countries you are being considered to work in making reasonable adjustments for disabled candidates We also collect data so that we can carry out activities which are in the legitimate interests of RQM+. We have set these out below: ensuring confidentiality making decisions about who to offer employment to making decisions about salary and other benefits assessing training needs keeping in touch with you for future employment opportunities dealing with legal claims made against us If you are unsuccessful in obtaining employment, as we operate in such a specific sector, we will hold your data to make contact with you in case other suitable job vacancies arise in RQM+ for which we think you may wish to apply. You may at any time contact us and ask us to stop doing this. Special categories of data Special categories of data are data relating to your: health disabilities gender expression sexual orientation race ethnic origin political opinion religion trade union membership and genetic and biometric data We must process special categories of data in accordance with more stringent guidelines. Most commonly, we will process special categories of data when the following applies: you have given explicit consent to the processing we must process the data in order to carry out our legal obligations we must process data for reasons of substantial public interest you have already made the data public We will use your special category data: to consider reasonable adjustments for disclosed disabilities in relation to our application, selection and offer processes We do not need your consent if we use special categories of personal data in order to carry out our legal obligations or exercise specific rights under employment law (article 9 GDPR). However, we may ask for your consent to allow us to process certain particularly sensitive data. If this occurs, you will be made fully aware of the reasons for the processing. As with all cases of seeking consent from you, you will have full control over your decision to give or withhold consent and there will be no consequences where consent is withheld. Consent, once given, may be withdrawn at any time. There will be no consequences where consent is withdrawn. IF YOU DO NOT PROVIDE YOUR DATA TO US One of the reasons for processing your data is to allow us to carry out an effective recruitment process. Whilst you are under no obligation to provide us with your data, we may not be able to process, or continue with (as appropriate), your application in the absence of this information. SHARING YOUR DATA Your data will be shared with colleagues within RQM+ where it is necessary for them to undertake their duties with regard to recruitment. This includes, for example, Company managers, Recruiters, Resourcing, HR, those in the department where the vacancy is who are responsible for screening your application and interviewing you. Your data may also be shared externally with our clients for the purpose of assessing your suitability for a role, RQM+ IT contractors where you require access to our systems and our HR/recruitment consultants who may support us in our recruitment and selection processes. In some cases, we will collect data about you from third parties, such as employment or recruitment agencies. Your data will be shared with third parties if you are successful in your job application. In these circumstances, we will share your data in order to obtain references, personality profiling, to obtain a criminal records check, background checks or credit check as appropriate as part of the recruitment process. We may also share your data with third parties as part of a Company sale or restructure, or for other reasons to comply with a legal obligation upon us. RQM+ does not and will not sell your data or any personal data to any third party for any reason. As a globally operating organisation RQM+ may be required to transfer personal data to countries between the USA, EEA, UK and also outside of those countries/jurisdictions. We have put the following measures in place to ensure that your data is transferred securely and that the bodies who receive the data that we have transferred process it in a way required by Data Protection Legislation: Using IT systems with data security assurance to access data from overseas Utilizing portals and other methods for transferring data securely Using encryption if sending high risk data by email Data protection training for overseas data processors Procedures for storing and processing data to Data Protection Legislation standards PROTECTING YOUR DATA We are aware of the requirement to ensure your data is protected against accidental loss or disclosure, destruction, and abuse. We have implemented processes to guard against such. E.g., backing up our servers, firewalls, access control for personal information, using password protected documents and encryption when transferring sensitive data, ensuring our IT systems that process personal information are secure to Data Protection Legislation requirements. Where we share your data with third parties, we provide written instructions to them to ensure that your data is held securely and in line with Data Protection Legislation requirements. Third parties must implement appropriate technical and organisational measures to ensure the security of your data. HOW LONG WE KEEP YOUR DATA FOR In line with data protection principles, we only keep your data for as long as we need it for and this will depend on whether or not you are successful in obtaining employment/work with us. If your application is not successful, we will keep your data for the purpose of contacting you for future work opportunities for a period of 5 years once the recruitment exercise ends. At the end of this period, we will delete or destroy your data, unless you grant us specific consent to our processing of your data for a further period. If your application is successful, your data will be kept and transferred to the systems we administer for employees, workers and sub-contractors. We have a separate privacy notice for employees, workers and sub-contractors, which will be provided to you. AUTOMATED DECISION MAKING No decision will be made about you solely on the basis of automated decision making (where a decision is taken about you using an electronic system without human involvement) which has a significant impact on you. YOUR RIGHTS IN RELATION TO YOUR DATA Data Protection Legislation gives citizens and residents in certain jurisdictions rights in relation to the data we hold. Although these rights may not be rights to citizens and residents in some countries and jurisdictions where Data Protection Legislation is limited, RQM+ extends these privileges to all. These are: the right to be informed. This means that we must inform you what data we hold, how we use your data, data that may be disclosed and this is the purpose of this privacy notice the right of access. You have the right to access the data that we hold on you. To do so, you should make a subject access request or in California, a consumer request the right for any inaccuracies to be corrected. If any data that we hold about you is incomplete or inaccurate, you are able to require us to correct it the right to have information deleted. If you would like us to stop processing your data, you have the right to ask us to delete it from our systems where you believe there is no reason for us to continue processing it. Under certain circumstances we may not be able to delete your data and where this is the case, we will confirm the reasons to you the right to restrict the processing of the data. For example, if you believe the data we hold is incorrect, we will stop processing the data (whilst still holding it) until we have ensured that the data is correct the right to portability. You may transfer the data that we hold on you for your own purposes the right to object to the inclusion of any information. You have the right to object to the way we use your data where we are using it for our legitimate interests the right to regulate any automated decision-making and profiling of personal data. You have a right not to be subject to automated decision making in way that adversely affects your legal rights You will not be discriminated against if you exercise any of your rights as detailed above including: Not considering you for employment or sub-contractor opportunities with RQM+ Excluding you from general communications provided to candidates Where you have provided consent to our use of your data, you also have the unrestricted right to withdraw that consent at any time. Withdrawing your consent means that we will stop processing the data that you had previously given us consent to use. There will be no consequences for withdrawing your consent. However, in some cases, we may continue to use the data where so permitted by having a legitimate reason for doing so. If you wish to exercise any of the rights explained above, please contact the Data Controller listed above. MAKING A COMPLAINT If you think your data protection rights have been breached in any way by us, you should contact our Data Protection Officer at dpo@rqmplus.com. If you think your data protection rights under GDPR or UKDPA have been breached in any way by us, you are able to make a complaint to a supervisory authority. In the UK, the supervisory authority is the Information Commissioner (ICO) – ico@org.uk  ABOUT RQM+ RQM+ as referred to in this document includes the following companies: RQM+ Corporation Regulatory and Quality Solutions, doing business as RQM+ R&Q Regulatory and Quality Solutions West, doing business as RQM+ West Maetrics LLC, doing business as RQM+ Maetrics Maetrics Limited, trading as RQM+ Maetrics GmbH, trading as RQM+ RQM+ (Germany) GmbH, trading as RQM+ Updated December 2023 #### Careers At RQM+, we know the success of our company and the success of our employees go hand in hand. That’s why we offer a compelling employee experience and are committed to helping you be your best. Find your next purpose-driven career move. Search Job Openings What Guides Us We take pride in fostering a rewarding culture by...​​ Our Core Values At RQM+, our core values shape how we work, collaborate, and contribute to the success of our clients — and ultimately, to improving patients’ lives. Maintain the highest level of integrity “The caliber of people who work here is amazing. We have so many smart, kind, decent, and caring people, and that is so nice. From the minute I started, I felt so welcomed and included. Great job on making sure you hire team players, people willing to collaborate and compromise and be just overall kind and decent people.” Be courageous, proactive, and figure it out to achieve the highest level of success “We get to work on projects that directly affect patients. I feel grateful that I can work with Tier 1 companies and see the product I've worked on 'in the wild.' I appreciate that my scientific training and experience are so well-suited to my work here and appreciated by clients.” Laser focus on customer success “I would recommend working at RQM+ because you work with a range of clients, helping them achieve compliance. You help ensure safe and effective medical devices are placed on the market.” Operate as a cohesive team… who likes to have fun “The work/life balance is unmatched and the ability to network with such a breadth of expertise and experience is an incredible asset.” Improve all the time “It's a caring and balanced culture that is remains driven to achieve greatness which gives confidence in the company and growth opportunities.” Share concerns and follow up with a thoughtful solution “I would recommend working at RQM+ because the work/life balance is unmatched and the ability to network with such a breadth of expertise and experience is an incredible asset.” Communicate… effectively and proactively “I find meaning in working with my team to find technical solutions that help our clients and promote safe and effective medical devices. Great team.” Live by the golden rule “I cannot get over how kind and intelligent everyone is. I feel safe and heard every time I speak. I love the work life balance I have here.” DEIB Statement At RQM+ we promote equity for all by empowering our people to participate, learn, and excel. We embrace our individual talents and harness them to a common purpose. Together, we strive to create and sustain an inclusive and equitable environment where all employees feel a sense of belonging, respect, and acceptance.  We create a culture that attracts and retains brilliant talents of all backgrounds and cultures while advancing global healthcare through MedTech innovation. Collectively, we help bring innovative, safe, and effective medical technology to the patients who need it most within the global communities we serve. Join Our Team Where Passion Meets Purpose Working at RQM+ isn’t just a job—it’s a chance to make a real impact. Here, your career is more than a path forward; it’s a platform for growth, innovation, and purpose. Explore our open positions and discover how your next move can help shape the future of MedTech. Find purpose in every step. #### Chemical & Cosmetic When accuracy is critical, RQM+ delivers expert chemical testing services designed to meet the unique needs of manufacturers in these highly regulated industries.   From regulatory compliance to product safety, our advanced analytical methods provide the insights you need to confidently and quickly bring your products to market.  Start Now  Chemical Lab Testing Benefits Partnering with RQM+ for chemical lab testing ensures: Core Chemical Lab Testing Services Our chemical lab testing services include: Chemical Characterization Advanced techniques for extractables and leachables (E&L) testing  Identification and quantification of organic and inorganic compounds  Comprehensive risk assessments for ISO 10993 compliance Consumer Product Testing Safety and stability testing for consumer products  Ingredient analysis and impurity identification  Regulatory documentation support for FDA and EU requirements  Product Deformulation Reverse engineering of chemical formulations for quality control and competitor analysis Identification of active and inactive ingredients in complex mixtures Support for intellectual property claims, regulatory compliance, and formulation optimization  Failure Investigations Root cause analysis for manufacturing defects and material inconsistencies  Guidance on corrective actions to prevent future issues  Biological Evaluation Support Toxicological assessments to ensure product safety  Support for biocompatibility testing under global regulations  Chemical Testing Results That Add Clarity and Compliance Expert Biocompatibility Testing Comprehensive testing capabilities aligned with ISO 10993 standards to ensure product safety and compliance Regulatory Support for Innovative Formulations Guidance tailored to meet FDA and international compliance requirements for chemical and consumer products Contamination Analysis and Solutions Identification and resolution of material issues to support product integrity and accelerate time to market  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  #### Client Privacy Statement Privacy Policy Candidate Privacy Statement Client Privacy Notice RQM+ is committed to processing your data securely and transparently. This privacy notice sets out the types of data that we collect and hold on you as a client or potential client of the company. It also sets out how we use that information, how long we keep it for and other relevant information about your data. RQM+ is aware of its obligations to residents and citizens of the EU under the General Data Protection Regulation (GDPR), of the UK under the Data Protection Act (UKDPA), of the USA under a variety of legislation and acts that include data protection requirements - specifically including the California Consumer Privacy Act (CCPA), of Switzerland under the Data Protection Act (DPA) and the Data Protection Ordinance (DPO), and the data protection requirements of residents and citizens of other countries, This privacy notice complies with the requirements of GDPR, UKDPA, CCPA, DPA and DPO and is applicable globally but may be supplemented by additional information on our privacy practices that may be provided as required by applicable laws and regulations via notices provided at the time of data collection. Together, these are referred to as “Data Protection Legislation”. This notice applies to individuals who are: Clients - individuals who represent (or represented) a company who RQM+ has or had a binding contract with to deliver services Potential Clients - individuals who represent (or represented) a company who RQM+ has or is currently discussing potential opportunities or contracts with for the delivery of services. Also individuals who represent (or represented) a company who RQM+ is developing a relationship with in regards to business development DATA CONTROLLER DETAILS The Company is a data controller, meaning that it determines the processes to be used when using your personal data. The company has appointed Data Protection Officers who are responsible for ensuring your data is stored and processed in accordance with this privacy notice. Data Protection Officers can be contacted at dpo@rqmplus.com  DATA PROTECTION PRINCIPLES In relation to your personal data, we will: process it fairly, lawfully and in a clear, transparent way collect your data only for reasons that we find proper for the course of your relationship with RQM+ in ways that have been explained to you only use it in the way that we have told you about ensure it is correct and up to date keep your data for only as long as we need it process it in a way that ensures it will not be used for anything that you are not aware of or have consented to (as appropriate), lost or destroyed. TYPES OF DATA WE PROCESS We may hold many types of data about you, including: your personal details including your name, address, e-mail address, phone numbers job title and job descriptions job responsibilities employer (and previous employers if known) who you report to your location country that you reside in information accessed and downloaded from company websites events attended and met with RQM+ representatives records of your contact with RQM+ marketing material and campaigns that you have shown an interest in. We do not request, hold or process special categories of data (such health, sexual orientation, race, ethnic origin, political opinion, religion, trade union membership and genetic and biometric data) or criminal conviction data for clients or potential clients. HOW WE COLLECT YOUR DATA We collect data about you in a variety of ways and we would normally collect the data from you directly. This will usually start when you contact us or talk to us about a business need you or your company has, but can also be when you have provided your details to access and download information from our website or shown an interest in specific topics of a marketing campaign. Further information may be collected directly from you as our relationship and correspondence increases. In addition, data about you may be obtained from other sources including from your colleagues as the person to speak to regarding a business opportunity or need, from publicly available sources or third parties such as LinkedIn and Zoominfo. Where this is the case, data that we hold will be limited in nature. WHY WE PROCESS YOUR DATA The laws on data protection allows us to process your data. Data Protection Legislation allows us to process your data for certain reasons which are detailed below: where we have your consent to do so in order to perform the contracts that we are party to in order for us to carry out our legitimate interests in order to carry out legally required duties to protect your interests and where something is done in the public interest. All of the processing carried out by us falls into one or more of the permitted reasons. Generally, we will rely on performance of contracts and legitimate interest to process your data. We need to collect your data so that we can perform and meet our obligations under the contracts we are part to for delivering agreed services. We also collect data so that we can carry out activities which are in the legitimate interests of the Company. We have set these out below: discuss and secure future business opportunities business pipelining making decisions regarding marketing activities analyse the effectiveness of marketing activities market intelligence including analysing the needs and potential need within the life science industry maintaining effective correspondence and relationships ensuring effective business administration business forecasting including business planning and growth & restructuring exercises achieving legal compliance and dealing with legal claims made against us preventing fraud ensuring our administrative and IT systems are secure and robust against unauthorised access. With your consent, we collect your personal data to be able to include you on regular company e-mails and marketing correspondence (see separate Contact Privacy Notice). IF YOU DO NOT PROVIDE YOUR DATA TO US One of the reasons for processing your data is to allow us to carry out our deliverables in line with our contractual obligations. If you do not provide us with the data needed to do this, we will be unable to perform those duties e.g. carry out an audit, attend site, provide consultancy, supply labour. Likewise, we may be unable to provide or agree contracts with you. SHARING YOUR DATA Your data will be shared with colleagues within RQM+ where it is necessary for them to undertake their duties. This includes, for example, Business Development who maintain contact and build relationships with you, Client Services and Clinical Services Management to work alongside you by managing projects and RQM+ resources working on your projects, RQM+ management and administration to oversee sales, contracts, invoicing and company operations, Resource Management, Corporate Recruiters, Resourcing and Business Development to discuss your resource needs and liaise with you on submitted candidates. We share your data with third parties in order to obtain legal support and business advice and when applicable, to obtain quotations on your behalf, work with third parties as required in Statements of Work. We may also share your data with third parties as part of a Company sale or restructure, or for other reasons to comply with a legal obligation upon us. RQM+ does not and will not sell your data or any personal data to any third party for any reason. As a globally operating organisation RQM+ may be required to transfer personal data to countries between the USA, EEA, UK and also outside of those countries/jurisdictions. We have put the following measures in place to ensure that your data is transferred securely and that the bodies who receive the data that we have transferred process it in a way required by Data Protection Legislation: Using IT systems with data security assurance to access data from overseas Using encryption if sending high risk data by email Data protection training for overseas data processors Procedures for storing and processing data to Data Protection Legislation requirements PROTECTING YOUR DATA We are aware of the requirement to ensure your data is protected against accidental loss or disclosure, destruction and abuse. We have implemented processes to guard against such. E.g., backing up our servers, firewalls, access control for personal information, using password protected documents and encryption when transferring sensitive data, hard drive encryption on all laptops, ensuring our IT systems that process personal information are secure to Data Protection Legislation standards. Where we share your data with third party suppliers, we ensure that the contracts between RQM+ and the third-party provider that your data will be held securely and in line with Data Protection Legislation requirements. Third parties must implement appropriate technical and organisational measures to ensure the security of your data. Where needed, a separate Non-Disclosure Agreement (NDA) is also signed. HOW LONG WE KEEP YOUR DATA FOR In line with data protection principles, we only keep your data for as long as we need it for. As a consulting company, we build long term relationships with individuals and companies. The history and the contact we have with you is an important factor in the relationships that we build for business development purposes. In the niche market of life science regulatory and quality compliance, individual standards, rules and regulations change from every three to four years with more substantial changes occurring every 10-15 years. Thus, it is possible that a client or potential client may only require our services on an infrequent basis. For Clients, we will hold data in order to perform the contracts that we are party to. We hold data to continue our relationship with you by understanding services we have delivered to you, potential services we have discussed with you and as a legitimate business interest to identify future opportunities to work with you again. We will retain data for 10 years after the last item of work in a SOW has been delivered and invoiced and/or the last opportunity for work was closed. For Potential Clients, we hold data to continue our relationship with you by understanding services we have previously discussed with you and as a legitimate business interest to identify opportunities to work with you in the future. We will retain data for 10 years after the last item of work in a SOW has been delivered and invoiced and/or the last opportunity for work was closed. We also hold data for individuals who do not wish to hear from us and individuals we may not wish to do business with. We have a legitimate business interest in holding this data to ensure that our employees do not contact those individuals inadvertently. AUTOMATED DECISION MAKING No decision will be made about you solely on the basis of automated decision making (where a decision is taken about you using an electronic system without human involvement) which has a significant impact on you. YOUR RIGHTS IN RELATION TO YOUR DATA Data Protection Legislation gives citizens and residents in certain jurisdictions rights in relation to the data we hold. Although these rights may not be rights to citizens and residents in other countries and jurisdictions where Data Protection Legislation is limited, RQM+ extend these privileges to all. These are: the right to be informed. This means that we must inform you what data we hold, how we use your data, data that may be disclosed and this is the purpose of this privacy notice the right of access. You have the right to access the data that we hold on you. To do so, you should make a subject access request or if California, a Consumer request the right for any inaccuracies to be corrected. If any data that we hold about you is incomplete or inaccurate, you are able to require us to correct it the right to have information deleted. If you would like us to stop processing your data, you have the right to ask us to delete it from our systems where you believe there is no reason for us to continue processing it. Under certain circumstances we may not be able to delete your data and where this is the case, we will confirm the reasons to you the right to restrict the processing of the data. For example, if you believe the data we hold is incorrect, we will stop processing the data (whilst still holding it) until we have ensured that the data is correct the right to portability. You may transfer the data that we hold on you for your own purposes the right to object to the inclusion of any information. You have the right to object to the way we use your data where we are using it for our legitimate interests the right to regulate any automated decision-making and profiling of personal data. You have a right not to be subject to automated decision making in way that adversely affects your legal rights. You will not be discriminated against if you exercise any of your rights as detailed above including: Denying services to you Charging you a different price for services, including granting discounts or other benefits or imposing penalties Providing you with a different level of service Suggesting that you may receive a different rate or level of service Where you have provided consent to our use of your data, you also have the unrestricted right to withdraw that consent at any time. Withdrawing your consent means that we will stop processing the data that you had previously given us consent to use. There will be no consequences for withdrawing your consent. However, in some cases, we may continue to use the data where so permitted by having a legitimate reason for doing so. If you wish to exercise any of the rights explained above, please contact the Data Protection Officers listed above. MAKING A COMPLAINT If you think your data protection rights have been breached in any way by us, you should contact our Data Protection Officer at dpo@rqmplus.com. If you think your data protection rights under GDPR or UKDPA have been breached in any way by us, you are able to make a complaint to a supervisory authority. In the UK, the supervisory authority is the Information Commissioner (ICO) – ico@org.uk  ABOUT RQM+ RQM+ as referred to in this document includes the following companies: RQM+ Corporation Regulatory and Quality Solutions, doing business as RQM+ R&Q Regulatory and Quality Solutions West, doing business as RQM+ West Maetrics LLC, doing business as RQM+ Maetrics Maetrics Limited, trading as RQM+ Maetrics GmbH, trading as RQM+ RQM+ (Germany) GmbH, trading as RQM+ Updated December 2023 #### Clinical Trials Clinical trials that deliver quality data are the bridge between innovation and positive human impact. At RQM+, The MedTech CRO, we use our deep operational and therapeutic expertise to provide end-to-end clinical trial services that are tailored to the unique needs of the MedTech industry.   With expertise across trial types – including early feasibility, pilot, pivotal, and post-market studies – and a focus on compliance, safety, and operational efficiency, we safeguard your journey to reliable results, meaningful outcomes, and informed decisions about your next steps. Want to deliver safe and effective medical devices to patients? Let’s make your MedTech happen.  Start Now  Clinical Trial Services Built for Your Success We provide end-to-end clinical trial management solutions that are designed to deliver quality data to advance your MedTech journey. With streamlined operations, deep therapeutic expertise, and insights you can actually use, we ensure compliance, efficiency, and patient safety every step of the way.  Our services include: Custom Trial Design Tailored EFS to pilot, pivotal, and post-approval studies designed by leading experts  Functional Support Project management, site feasibility, strategy and activation, data management, medical affairs and product safety, clinical site management, CEC/DMC adjudication management and reporting, biostatistics, and medical writing  Global Expertise Seamless compliance with U.S., EU, and international regulatory requirements  Therapeutic Focus Areas We have comprehensive expertise across a wide range of therapeutic areas, with specialized focus areas for Medical Devices and IVD: Medical Device: Cardiology  Orthopedics Neurology Oncology Ophthalmology Dermatology Endocrinology Gastroenterology Respiratory Care IVD: Infectious Disease​ Oncology & Companion​ Chronic Disease & Metabolic Disorders​ Hematology & Immunology​ Neurology & Neurodegenerative Disorders​ Women’s & Reproductive Health​ Genetic & Molecular ​ Gastrointestinal Why Choose Us? Why partner with RQM+ for your clinical trial consulting and management needs? Let’s count the ways:  “The efficiency and collaboration of the RQM+ team in conducting our IVD clinical study was exceptional. The collaboration across the US and EU geographies was seamless. We have found our go-to CRO partner for future IVD projects.” Laboratory Manager, Global IVD Manufacturer “RQM+ was extremely professional, prompt and easy to work with on the Animal Tissue Literature Review project. Everyone we worked with was very friendly and made our lives simpler. The report that was put together fit our exact needs and expectations. We hope to work with RQM+ more in the future.” Senior Quality Engineer, Innovative MedTech Company “The team was very friendly and professional, easy to work with.” Senior Regulatory Affairs Specialist, Global Medical Device Manufacturer Expertise Across Diverse Industry Segments Clinical Trial Success Stories  Successfully managed trials across 20+ therapeutic areas, including oncology, cardiovascular, urology, and neurology  Achieved timely approvals for 510(k) and PMA applications through optimized trial and regulatory strategies  Delivered data integrity and actionable insights that shaped regulatory submissions and market access strategies  Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Coding & Billing Effective coding and billing are the backbone of successful MedTech reimbursement strategies. We specialize in developing and securing accurate Healthcare Common Procedure Coding System (HCPCS) and Current Procedural Terminology (CPT) codes, ensuring MedTech market access. With deep industry expertise and strong relationships with key stakeholders — including medical societies and the Centers for Medicare and Medicaid Services (CMS) — RQM+ streamlines the coding process and eliminates barriers.   Our coding and billing services for MedTech help your technology reach patients faster.  Start Now  Coding and Billing Benefits When you partner with RQM+ for MedTech market access guidance, you gain:  Core Coding and Billing Services HCPCS and CPT Code Development  Submission of applications for new and revised codes  Guidance on coding strategies to optimize reimbursement potential Code Analysis Review of existing codes to align with payer policies  Recommendations for code updates to address gaps in coverage or payment  Stakeholder Engagement Advocacy with CMS, private payers, and medical specialty societies  Creation of clinical and reimbursement dossiers to support coding initiatives  Comprehensive Support Coding integration with reimbursement and regulatory strategies  Insights into global coding requirements for international market access  Demonstrated Coding and Billing Success  Successfully supported top 20 pharma clients in securing HCPCS and CPT codes to align with payer requirements and optimize reimbursement  Developed robust coding strategies to address gaps in payer recognition  Partnered with clients to align coding, coverage, and payment strategies with CMS and private payer standards  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  #### Combination Products Combination products represent the forefront of innovation, merging the best of drug, biologic, and device technologies to revolutionize patient care. However, their complexity demands expert integration of regulatory, clinical, and commercialization strategies. RQM+ is your combination product consulting lifeline, uniquely positioned to guide you through the product life cycle from start to finish.   Our solutions for combination products ensure compliance, optimize performance, and accelerate patient access.  Start Now  Combination Products Consulting Benefits Integrated Life Cycle Approach: Beyond Compliance Combination products require both regulatory clearance and alignment across development, testing, and post-market phases. RQM+ supports you throughout the entire life cycle, ensuring compliance at every stage while optimizing speed to market: Development Strategic planning to meet drug-device combination requirements Testing Integrated biocompatibility and chemical characterization tailored to combination products Market entry Comprehensive submission packages and agency liaison Post-market Ongoing compliance monitoring and reporting aligned with MDR and FDA standards Gold standard lab& material science Industry-leading materials testing and chemical characterization recognized by the FDA Global reach Successful regulatory submissions across the U.S., Europe, and the U.K. Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. Life Cycle Support Expand each to see key services. 1. Design Concept Regulatory  Product classification (drug vs. device vs. biologic-led)  Primary mode of action (PMOA) analysis  Jurisdiction strategy (CDRH/CDER/CBER, EMA, NCAs)  FDA Intercenter Consult Request (ICCR) planning  EU: Borderline determination, EMA consultation  Global regulatory pathway strategy Documents: Regulatory strategy memo, PMOA justification, briefing documents  Quality  Risk management plan (ISO 14971)  Combination product development framework alignment  Device constituent quality planning  cGMP vs. QSR mapping Documents: Risk management plan, combination product quality plan  Clinical  Early feasibility assessments  Clinical development plan concept (drug + device integration)  Human factors planning Documents: Draft CDP, early clinical plan outline  Reimbursement  Combination product market and value proposition assessment  Reimbursement landscape across drug and device pathways Documents: Early reimbursement strategy memo, HTA readiness assessment  Labs (Jordi Labs)  Material selection and formulation consulting  Extractables/leachables strategy setup Documents: Material justification report, E/L testing strategy  Medical Writing  Draft TPP (Target Product Profile) including drug/device attributes  Early IFU/label concept drafts Documents: TPP draft, outline of clinical utility rationale 2. Design & Development Regulatory  Meeting requests and briefing packages (FDA/EMA)  Combination product classification confirmation  IND vs. IDE determination (US)  EMA drug-device consultation support Documents: Pre-sub/Q-Sub packets, EMA consultation dossiers  Quality  Design control documentation for device constituent  Integration of cGMP/QSR/QMS hybrid system  Supplier and component traceability Documents: DHF, DMR drafts, QMS alignment plan  Clinical  Protocol design with drug-device endpoints  Safety reporting structure planning (both CDER and CDRH/CDER split) Documents: Draft protocol, safety reporting SOPs  Reimbursement  Evidence-to-value strategy for hybrid pathways  Companion diagnostic and delivery method considerations Documents: Reimbursement roadmap, payer messaging alignment  Labs (Jordi Labs)  Extractables and leachables method development  Container/closure system compatibility Documents: Testing protocol, method validation reports (support only)  Medical Writing  Protocol authorship  Risk-benefit narrative development Documents: Draft protocol, target labeling document  3. Verification & Validation Regulatory  Verification and validation planning support (not execution)  Device constituent regulatory impact assessment Documents: Verification planning rationale, validation summary memo  Quality  Test method documentation support  Design validation documentation (support only) Documents: TMV protocol support, validation documentation templates  Clinical  Final protocol completion  Site qualification planning Documents: Final protocol, monitoring plan  Reimbursement  Coding implications of product configuration Documents: Coding rationale document  Labs (Jordi Labs)  Execution of E&L testing, biocompatibility  ISO 10993 testing strategy Documents: Biocompatibility reports, E/L test reports  Medical Writing  IFU drafts with validated content  Risk-based justification summaries Documents: IFU, Instructions for administration/use, Safety summary   4. Clinical Evidence Generation Regulatory  Clinical trial submission support (IND, IDE, CTAs)  Risk-based monitoring strategy consultation Documents: Clinical protocol, IND/IDE/CTA documentation  Quality  Clinical quality SOPs  GCP compliance guidance Documents: Clinical SOPs, monitoring logs  Clinical  Full trial execution (project management, monitoring, data management)  Real-world evidence setup if applicable Documents: CSR, study reports, safety summaries  Reimbursement  Clinical value justification  Economic endpoint strategy Documents: Value dossier contributions  Labs (Jordi Labs)  Stability testing  Product interaction evaluations Documents: Stability report, compatibility analysis  Medical Writing  CSR development  Clinical summaries for regulatory submission Documents: CSR, Summary of Clinical Safety, Summary of Clinical Efficacy   5. Manufacturing Readiness Regulatory  Drug-device combination compliance strategy (e.g., CFR 4)  EMA/Notified Body consultation Documents: Manufacturing SOPs (support), bridging justifications  Quality  Process validation documentation (support only)  Final DMR/DHF review Documents: Validation plan (documentation support), lot release SOPs  Clinical  Finalize IFU and training materials for HCPs Documents: Training plan, clinical performance checklist  Reimbursement  Payer-facing clinical utility justification Documents: Updated economic model or HTA pre-submission package  Labs (Jordi Labs)  Final E&L, stability, shelf-life support Documents: Final test reports  Medical Writing  Final IFU/label content  Manufacturing/administration documentation for submission Documents: Administration guide, packaging insert    6. Regulatory Submissions Regulatory  Submission compilation and formatting (eCTD, 510(k), PMA, BLA/IND)  Drug-device combination modules (Module 3, Annex I per MDR)  Responses to FDA/EMA/NB queries Documents: Full regulatory submission, RTA checklists, deficiency responses  Quality  Audit readiness support Documents: Audit response documents  Clinical  Clinical evaluation report (CER)  Clinical summaries (EU and US) Documents: CER, SSCP  Reimbursement  Health economics inclusion in submission (optional) Documents: HTA-ready value dossier sections  Labs (Jordi Labs)  Inclusion of full chemistry and toxicology package Documents: Chemical characterization summaries  Medical Writing  Compilation of technical documents  Regulatory writing support for submission documents Documents: Clinical Overview, 2.7.1–2.7.4 summaries  7. Market Access & Launch Regulatory  Global registrations  Labeling translation review (EU) Documents: Registration forms, packaging content  Quality  Post-market surveillance planning  Product complaint system setup Documents: PMS plan, complaint handling SOPs  Clinical  PMCF plan  Registry planning Documents: PMCF plan, RWD study framework  Reimbursement  Coding assignment (US: HCPCS, EU: NUB)  Payer engagement Documents: Coding request letters, coverage justifications  Labs (Jordi Labs)  Ongoing batch testing  Real-time aging studies Documents: Batch test reports  Medical Writing  PMCF study documents  Payer communication tools Documents: PMCF protocols, evidence summaries   8. Post-Market Activities Regulatory  Vigilance support  Periodic safety update reports (PSUR) Documents: PSUR, MDRs  Quality  CAPA system setup and oversight  Periodic audit support Documents: CAPA reports, internal audit plans  Clinical  PMCF surveys and studies Documents: PMCF reports, clinical update summaries  Reimbursement  HTA reassessment submissions Documents: Updated value dossiers  Labs (Jordi Labs)  Long-term stability and impurity profiling Documents: Updated test reports  Medical Writing  Safety summary reports  PMS-related narrative reports Documents: PSUR narrative, PMS summary   9. Design Changes, M&A, & Market Expansion Regulatory  Change impact assessments  Global change notification support Documents: Supplement submissions, change memos  Quality  Change control documentation  QMS integration planning (post-M&A) Documents: Updated SOPs, integration plan  Clinical  Bridging studies and labeling extensions Documents: Bridging protocol, justification memo  Reimbursement  Pricing update strategy Documents: Payer re-engagement materials  Labs (Jordi Labs)  New formulation testing  Comparative testing Documents: Side-by-side chemical assessments  Medical Writing  Update IFU, CERs, and submission modules Documents: Revised CER, Summary of Product Characteristics   10. Emergency Support Regulatory  Regulatory remediation (warning letter, CE mark suspension)  Emergency meeting request drafting and response strategy Documents: Remediation plans, briefing docs  Quality  CAPA plans under regulatory scrutiny  QMS overhaul under tight timelines Documents: CAPA logs, QMS revision memos  Clinical  Safety incident investigation  Emergency PMCF implementation Documents: Safety reports, rapid evidence summaries  Reimbursement  Payer renegotiation following adverse events Documents: Risk mitigation plan  Labs (Jordi Labs)  Confirmatory testing under urgent conditions Documents: Emergency test summary  Medical Writing  Root cause analysis documents  Urgent regulatory communications Documents: Safety notices, response narratives  Partner Testimonial “I have been working with RQM+ for the last couple of years. They have always been systematic and thorough in getting the documents completed on time. Very approachable to have any discussions or clarifications on the EU MDR process. Working with RQM+ has been a great experience.” Clinical Development Specialist, Global Medical Device Manufacturer “The teams worked great together to successfully deliver the Periodic Safety Update Report on time with no rework or change authorizations needed.” Post-Market Quality Assurance Specialist, Innovative MedTech Company Combination Products FAQs What is the impact of adding a recognized drug to my device? In the U.S., under the 510(k) process, it can be fairly straightforward on the submission side if you have a predicate that utilizes the same drug product at the same level. Adding an established drug that hasn’t been used in a device complicates the situation tremendously. It most likely will raise new questions of safety and performance leading to a de novo or PMA pathway. Adding a new chemical entity that functions as a drug will bring a consult from CDER on your device submission and all the testing to support the product just like a New Drug Application (NDA). In the EU, the answer is that if the drug is ancillary to the device, you will leap all the way to a Class III device under Rule 14 and the drug substance dossier will be reviewed in addition to your full technical documentation package at the NB. Entering into the combination product world also means you will have to follow additional quality system regulations including 21 CFR 4 in the U.S. I’m developing a combination product — do I need to submit a drug and a device application? While some combination products can rely on a single application to gain regulatory approval, the simple answer is this — it depends! There are two main factors that impact this decision: The intended market — U.S. and EU have key differences The type of combination product — There are regulatory differences for single-entity/integral products, co-packaged products, or cross-labeled products In the U.S., combination products that are single-entity or co-packaged products are assigned to a single FDA Center that will have primary jurisdiction for its premarket review and regulation based on the most important therapeutic action. Typically, only a single marketing application is necessary for these types of combination products although inter-agency consults may be utilized during the review of the application. In an example where the most important therapeutic action is the drug, then the product will require a drug application and will be regulated by CDER. During the drug application review, a consult with CDRH may be requested for the device constituent of the product. Conversely, if the most important therapeutic action is the device, then the product will require a device submission to CDRH and may include a CDER consult during the review. Products where the drug and the device constituents would be sold separately and labeled to be used together are considered cross-labeled combination products. For these products, each constituent would typically be regulated separately, and each product would require their own marketing applications to the appropriate FDA Centers. In the EU, Article 117 of the new EU MDR introduced new requirements for drugs with an integral medical device, which are equivalent to single-entity products in the U.S. Since 2021 the drug application will need to include a CE certificate for the device or include an opinion from a notified body on the conformity of the device if it is not CE marked. The notified body opinion could be obtained during the drug review if it is not separately CE marked. Devices with an integral medicinal product are automatically classified as Class III medical devices and may require a drug review to achieve CE marking. Co-packaged products are treated differently in the EU and would typically require separate device and drug applications. Cross-labeled products align with the U.S. in that CE marking is required separately from the drug application for these product types. Should I use the Pre-Request for Designation (Pre-RFD) process or the Request for Designation (RFD) process to determine what will be the lead FDA Center assigned to review my product? The Pre-RFD process is used to get informal and non-binding feedback from the FDA about your combination product, whereas the RFD process provides binding feedback through a formal process. The Pre-RFD is helpful early in the product development stages where you may want to understand how the agency is likely to designate the lead center for reviewing your combination product — CDER, CBER, or CDRH. The Pre-RFD process provides a flexible and approachable way to obtain informal feedback from the Agency about the type of marketing application and the lead FDA Center that is most likely to be assigned for review and regulation of the product. If you are in later stages of development and the device does not have a clear primary mode of action, then the formal RFD process provides a binding decision to assign the lead center for review. This process can be used to avoid rejection or delays in a marketing application if the classification or assignment is determined to be unclear or in dispute during the review process. It is important to note that a Pre-RFD or an RFD are not always required for a product. If the product is very similar to an existing product, then it is possible to rely on capsular decisions that are posted on the FDA website to understand how similar products have been assigned. I have a legacy drug product that is considered a combination product in the U.S. Do I need to make any changes to my quality system to ensure I’m meeting the combination product regulations? Yes, your drug quality system will need to be adjusted to comply with additional device quality system requirements under 21 CFR 820 for management responsibility, design controls, purchasing controls, corrective and preventive action, installation, and servicing. While many of these elements may be covered in Pharmaceutical Quality Systems, design controls is one element that typically poses the most significant challenge for drug manufacturers. Design controls are a systematic process to ensure the product design meets the user needs, the intended uses, and any specific regulatory requirements. The design process culminates in a design history file, or a DHF, that is maintained over the product lifecycle. Drug manufacturers often need to adjust their quality systems to meet these requirements and also perform DHF remediation to ensure that changes in the product are appropriately documented over the lifecycle. #### Companion Diagnostics (CDx) RQM+ delivers integrated and tailored regulatory, clinical, and market access support for pharmaceutical sponsors, biotech companies, and diagnostic developers advancing companion diagnostics (CDx) and precision medicine. Whether your goal is full commercial launch or obtaining the right regulatory clearance to support therapeutic clinical trials — such as IVDR compliance for performance studies in the EU — our MedTech experts provide fully integrated solutions to streamline approvals and align with drug development timelines. Start Now  Why RQM+ for CDx? Standards We Navigate FDA 21 CFR Parts 809, 812, 814 (PMA), and 820 IVDR (EU 2017/746), Article 2(7), 56-77, and Annex XIII and XIV EMA GVP and Companion Diagnostic Guidelines ISO 13485 and ISO 20916 ICH Q2(R2)/Q14 (analytical validation for biomarker assays) PMDA Companion Diagnostic Guidelines EUnetHTA HTA Core Model® for CDx value dossiers Companion Diagnostic Life Cycle Support Expand each to see key services. 1. Design Concept Regulatory  Biomarker-CDx alignment strategy for drug labeling  IUO/RUO vs. CDx classification guidance (US and EU)  EU IVD requirements for assays used in trials (require IVD certification even if investigational)  Companion diagnostic regulatory development roadmap  Quality  QMS gap analysis for diagnostic partners or labs  GCLP-compliant planning for assay use in clinical trials  Early quality system setup for future CDx or IUO alignment  Clinical  Biomarker and trial design strategy  Trial schema alignment to biomarker stratification (adaptive, enrichment models)  Clinical strategy to support therapeutic trial with investigational assay  EU: clinical evidence planning for IVDR if CDx transition is likely  Reimbursement  Early payer landscape assessment  Exploratory HEOR and diagnostic value modeling tied to drug indication  Medical Writing  Drafting biomarker rationale for protocols and investigator brochures  Positioning of assay as investigational in trial documents  EU-specific IFU (Instructions for Use) documentation for investigational IVDs  2. Design & Development Regulatory  IND or IDE regulatory strategy (if assay affects trial endpoints or subject stratification)  Companion diagnostic co-development alignment with therapeutic timeline  Pre-submission planning with FDA or Notified Body  Quality  Vendor qualification and audits (central labs, CROs, assay developers)  Quality documentation support for LDT or IUO under clinical trial use  CLIA, ISO 13485, and IVDR lab compliance review  Clinical  Protocol development including assay integration  Site and lab qualification  Biomarker stratification training and data capture plans  Reimbursement  Risk-based evidence plan for future payer support  Clinical utility framework for companion diagnostics  Medical Writing  Study protocol input (biomarker sections)  Informed consent language for assay use  Analytical validation plans and summaries  3. Verification & Validation Regulatory  Support for IUO documentation for IND or IDE  Evidence generation plan aligned to FDA and IVDR expectations  EU: confirmation of analytical performance as per IVDR Annex I  Quality  Design control documentation  Verification protocol support (analytical precision, accuracy, specificity)  Documentation to support regulatory submission or trial audit readiness  Clinical  Coordination of validation data with clinical endpoints  Analysis of biomarker-stratified outcomes  EU: Clinical performance data planning for IVD certification  Reimbursement  Incorporating real-world elements into validation design (where applicable)  Evidence mapping to potential HTA requirements  Medical Writing  Drafting validation reports (analytical and clinical)  Cross-linking assay performance to therapeutic claims  Preparing content for regulatory submission or scientific publication  4. Clinical Evidence Generation Regulatory  Regulatory support for clinical protocols and endpoints tied to biomarker use  EU: Ensuring IVD certificate or performance study application is in place  FDA meeting prep (Type C, Pre-Sub) for assay data  Quality  Oversight of assay use and data integrity during trials  Data traceability support for biomarker performance  Clinical  Trial execution support with embedded assay use  Risk-based monitoring of assay-related endpoints  Multi-arm and enrichment trial design consulting  Reimbursement  Capture of clinical utility evidence  Drafting of payer-facing clinical summaries post-trial  Medical Writing  Interim and final CSR sections related to biomarker and assay  Clinical evaluation reports for EU if conversion to CDx occurs  Regulatory briefing documentation  5. Regulatory Submissions Regulatory  Companion diagnostic module preparation for NDA/BLA/MAA  Standalone CDx PMA/510(k) submission support  EU: Performance evaluation reports, GSPR, Technical Documentation per IVDR  Quality  Final design history file and DHF compilation  Risk management file preparation  Traceability matrix linking assay to therapeutic use  Clinical  Final trial evidence summaries  Preparation for clinical site inspection or audits  Reimbursement  Dossier development for EU payers and US CMS engagement  Mapping evidence to coding/reimbursement pathways  Medical Writing  Submission-ready labeling, IFU, and summary of safety and performance  PMA/510(k) narrative components  EMA or NB response packages  6. Market Access & Launch Regulatory  Post-approval change support  Labeling alignment with drug  EU: Notified Body communication and updates  Quality  Supplier and lab network quality agreements  CAPA, complaint handling, and postmarket change management  Clinical  Postmarket performance studies (if required)  Evidence generation for new indications  Reimbursement  Payer engagement and evidence updates  Coding pathway activation (PLA, Z-code)  Medical Writing  Clinical utility publications  Label updates  HTA submission writing  7. Post-Market Activities Regulatory  Vigilance reporting (MDR)  Labeling change support  PMCF/PMPF plan development  Quality  Ongoing QMS support  Supplier audits  Complaint trending analysis  Clinical  PMCF study oversight  Registry participation and data integration  Reimbursement  Evidence refresh to maintain coverage  Price renegotiation strategy  Medical Writing  PMCF reports  Labeling changes  Scientific publications for long-term data  8. Emergency Support Regulatory  Response strategy for FDA/EMA/Notified Body  CAPA documentation  Reclassification strategy  Quality  Rapid QMS remediation  SOP gap analysis and rewrite  Field action documentation  Clinical  Root cause analysis of trial deviation or failure  Emergency study redesign  Reimbursement  Damage control with payers  Evidence remediation planning  Medical Writing  Crisis response documentation  Justification memos  Incident reports Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Cookies Policy Information About Our Use Of Cookies Our website uses cookies to distinguish you from other users of our website. This helps us to provide you with a good experience when you browse our website and also allows us to improve our site. A cookie is a small file of letters and numbers that we store on your browser or the hard drive of your computer if you agree. Cookies contain information that is transferred to your computer's hard drive. We use the following cookies: #### Emerging MedTech & Startups Emerging MedTech and startup companies drive innovation, often by addressing specific, unmet market needs. However, these organizations often face a special set of challenges – from limited resources to complex and unfamiliar regulatory pathways. RQM+ offers customized MedTech solutions with flexible ways of partnering for companies of all sizes. Let us help you overcome these barriers and make sure your innovative products reach the patients who need them. Whether you’re launching a new product, managing sustaining activities, or navigating remediation, we provide the strategic guidance you need to advance your program – faster, safer, better.   Make Your MedTech Happen What does that mean for your business? Explore how we support your product type Solutions Tailored for Smaller MedTech Companies We understand that growing MedTech companies require flexible, business-balanced solutions. RQM+ provides scalable, cost-effective support designed for startups, small, and mid-size organizations that need help overcoming regulatory challenges and accelerating market entry. No matter your stage of growth, our team of former regulators and industry experts guide you through every step of the MedTech lifecycle.   Regulatory & Quality: Expertise in regulatory compliance, quality management, and market access strategies   Clinical Trials: Complete support in designing, executing, and analyzing clinical studies to ensure product safety and effectiveness  Laboratory & Materials Analysis: Advanced testing solutions to assess material properties for quality, reliability, and compliance  Reimbursement Services: Personalized strategies to secure payer reimbursement for medical technologies  Right Partner = Right Solutions Our emerging partners often have clinical affairs managers who take on a broader range of tasks. In these cases, practical and resource-efficient solutions are even more critical to success. RQM+ specializes in delivering these solutions. Whatever your growth stage, therapeutic area, or product type, we collaborate closely with you to ensure your needs are met and your program fulfills its potential.   Proven Expertise at All Stages of Growth We’ve partnered with a wide range of emerging MedTech companies, building a track record of regulatory and market success.   #### Events URL: https://www.rqmplus.com/about-us/news-events/events/ #### Expertise When speed and certainty matter, trust RQM+. We bring 40+ years of MedTech expertise, 50+ years of direct FDA experience, and a legacy of leadership from top notified bodies like BSI and TÜV. We’re the trusted global partner for accelerating your device, diagnostic, or combination product to market. We are The MedTech CRO for all your needs. Talk to an Expert Accelerate Your Success Expertise throughout the entire development life cycle Access Device-Specific Expertise Whatever your MedTech area of need, we’ve got you covered. Expert Spotlight: Ronnie Mahofski Executive Vice President, Corporate Development  Ronnie Mahofski joined RQM+ in 2015 and now serves as the Executive Vice President of Corporate Development. He has extensive experience in strategic account development and mergers and acquisitions, having spearheaded several acquisitions for RQM+, and he excels at corporate development, commercialization, and operational excellence. Ronnie provides strategic leadership across RQM+ initiatives, ensuring our clients receive tailored solutions to achieve market success. Learn more about our Regulatory and Quality Solutions Expert Spotlight: David Novotny Chief Operating Officer, Trial Services As Chief Operating Officer of Trial Services, David leads the RQM+ clinical trials division. David has more than 20 years of leadership experience with trial operations, consulting, and device research across North America, Europe, and Asia-Pacific. He previously served in strategic leadership positions at global MedTech CROs.  Learn More About Clinical Trials Expert Spotlight: Kevin Rowland Executive Vice President & General Manager, Lab Services​  Kevin received his bachelor’s degree in ceramic engineering in 2001, followed by a master’s degree in 2003 in materials science and engineering — both from Alfred University. He then received a master’s degree in chemistry from Brown University under Dr. Brian Moulton in 2008 with research focusing on molecular self-assembly. Kevin has been at Jordi Labs (now part of RQM+) since 2009 and has served as team leader for the GCMS and LCMS groups as well as laboratory manager. His work has focused on interpretation of high-resolution accurate mass MS data for identification of non-target, unknown compounds.   Learn More About Lab & Material Science Expansive Therapeutic Expertise Our expertise spans a wide range of therapeutic areas:  Medical Device: Cardiology  Orthopedics Neurology Oncology Ophthalmology Dermatology Endocrinology Gastroenterology Respiratory Care IVD: Infectious Disease​ Oncology & Companion​ Chronic Disease & Metabolic Disorders​ Hematology & Immunology​ Neurology & Neurodegenerative Disorders​ Women’s & Reproductive Health​ Genetic & Molecular ​ Gastrointestinal "Extremely happy with RQM+. My main interaction is with our lead consultant, who is a well-experienced expert that serves our company with distinction. Whenever it is necessary to consult, there are always experts within RQM+ to draw on." President and Chief Scientific Officer, Global Medical Device Manufacturer "During the project conduction, the RQM+ team was quick responding and gave a lot of professional suggestions to develop the clinical documents." Product Manager, Global Medical Device Manufacturer "RQM+ was extremely professional, prompt and easy to work with on the literature review project. Everyone we worked with was very friendly and made our lives simpler. The report that was put together fit our exact needs and expectations. We hope to work with RQM+ more in the future." Senior Quality Engineer, Innovative MedTech Company "It was a pleasure working with the entire team at RQM+ on our sterilization validation review project. As always, everyone at RQM+ is extremely professional, flexible, and always available and willing to go above and beyond. In addition to the annual sterilization reviews, our team had a lot of requests this year related to sterilization changes. Your guidance was invaluable. We were able to meet our timeline for the completion of the sterilization reviews and were complimented by or notified body on the content and process used. We look forward to working with you again!" Sr. Quality Systems Engineer, Global Medical Device Manufacturer "I have been working with RQM+ for the last couple of years. They have always been systematic and thorough in getting the documents completed on time. Very approachable to have any discussions or clarifications on the EU MDR process. Working with RQM+ has been a great experience." Clinical Development Specialist, Global Medical Device Manufacturer "Great team, great knowledge and insights in helping small, young startups navigate gaining clearance from FDA on new devices." COO, Global Medical Device Manufacturer "Our technical lead is the best we've had from RQM+ so far. She was an SME, extremely organized and knowledgeable and an absolute pleasure to work with. She was meticulous, disciplined and had a great team spirit. She gave the program a new life and we feel incredibly fortunate to have worked with her." Clinical Project Manager, Clinical Affairs, Breast and Skeletal Health Innovative MedTech Company "Our collaboration with RQM+ was very smooth and we are very happy with the end result of our first project." Project Management Team Lead, Contract Testing Laboratory "Our regulatory specialist did a great job in not only generating maintaining and adjusting the Gantt chart, but also in facilitating areas than needed action to assure the team stayed on schedule." Director Product Development R&D, Innovative MedTech Company "RQM+ has been very helpful and great to work with, very thorough, organized, accommodating and knowledgeable." Senior Manager, Clinical Affairs, Operations Innovative MedTech Company "The RQM+ lead has been a great asset to multiple projects for us. Our teams love working with her. RQM+ has made the process of adding short term talent to our teams easy and painless." Associate Director, Project Management, Global Medical Device Manufacturer "We were happy to find the right skillset from your resources to meet our project needs." Sr Specialist Regulatory Affairs, Global Medical Device Manufacturer "Great company to work with. Meetings provided visibility and progress on the project. Excellent communication and timely response to questions." Head of Quality-Biologics Midwest Cluster, Innovative MedTech Company "Our team lead is very responsive and knowledgeable about both our system and FDA regulations. She brings in help when she needs to, and I see motivation as very well taken care of." COO, Innovative MedTech Company "I cannot think of anything negative in my experience with RQM+ so far. Everyone has been great to work with." Program Director, Global Medical Device Manufacturer "Our project lead has been a true asset: always responsive and thorough, no matter what we ask." Global Clinical Development Manager, Patient Care Solutions - Consumables, Global Medical Device Manufacturer #### Full Site Map URL: https://www.rqmplus.com/full-site-map-36/ #### Health Economics Securing reimbursement for MedTech innovations often hinges on demonstrating their economic value. At RQM+, our health economics consulting and related services provide comprehensive analyses that quantify the cost-effectiveness of your products. This helps you build a compelling case for payer support.   From robust cost analyses to health economic studies, we help you navigate payer landscapes with confidence.  Start Now  Health Economics Benefits Partnering with RQM+ for health economics services delivers important benefits:  Core Health Economics Services Cost Analysis Detailed accounting of expenses associated with medical devices and programs  Support for policy and program decision-making through financial transparency Cost-Effectiveness Analysis (CEA) Comparative evaluations of technologies and procedures with similar outcomes  Quantifiable insights to position your product as a superior choice for payers Cost-Benefit Analysis (CBA) In-depth comparison of benefits and costs tied to your innovation  Evidence-based recommendations to strengthen your market access strategy Health Economic Modeling Development of models to predict economic impact and adoption rates  Data-driven strategies to optimize pricing and positioning Our Health Economics Track Record  Collaborated with clients to develop cost-effectiveness analyses that secured reimbursement approvals for breakthrough medical devices  Delivered economic models that demonstrated value propositions and led to accelerated payer acceptance  Supported health economic analyses for top-tier MedTech companies for successful entry into global markets  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  #### Home Default Heading This is the default text for the paragraph block. As The MedTech CRO, RQM+ makes MedTech happen by accelerating innovation from concept to patient impact. Our tailored solutions throughout the product life cycle deliver regulatory and quality expertise, FDA-recognized laboratory services, clinical trials, and reimbursement strategies across device types and therapeutic areas to bring life-changing technologies to patients — faster, safer, better. MedTech Solutions for Every Stage of Your Product’s Life Cycle We provide tailored expertise across four core service and diverse therapeutic areas to advance your MedTech product from concept to market. Why RQM+ Guiding your MedTech journey with faster solutions, fewer obstacles, and complete support from start to finish. Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. Delivering Real Results Real results that demonstrate our expertise and commitment to your MedTech success: 40+ Yearsof Expertise Delivering regulatory and quality (RA/QA) consulting excellence. 19 of the Top 20 MedicalDevice Companies Trusted by industry leaders worldwide. 7 of the Top 10 IVDCompanies Chosen by innovators for their most critical projects. 50% EfficiencyGain Achieved through our proprietary technology platforms. Gold Standard Lab & Material Science Through Jordi Labs Industry-leading materials testing and chemical characterization recognized by the FDA. Global Reach Successful regulatory submissions across the U.S., Europe, and the U.K. Make Your MedTech Happen Hear From Our Clients Trusted by industry leaders to simplify the complex and help bring life-changing innovations to market. “Highly recommend. I have been working with RMQ+ for the past 3 years and am very thankful for all the help and indispensable knowledge the team has brought to my organization. RQM+ talented members have helped make complex projects easy to manage and enabled our submissions to be successful. I couldn't ask for a better company to partner with.” Regulatory Compliance Manager, Innovative MedTech Company “I found the people who I've worked with from RQM+ to be professional, knowledgeable, and friendly. It was a pleasure to work with your team! I would recommend RQM+ to a colleague without any hesitation. I would look forward to working with RQM+ on other projects in the future. Your team would be my first choice when looking for external support, should the need arise.” Director of Quality Systems and Regulatory Affairs, Global Medical Device Manufacturer “Very happy with ongoing support and always quick, proactive response to need for help. Very happy with expertise and guidance provided by RQM+.” Senior Director, Innovative MedTech Company “RQM+ provided great team work with me during the external support, the communication is good and response is fast.” Clinical Product Manager, Global Medical Device Manufacturer “RQM+ have been incredibly professional, knowledgeable, efficient and patient throughout our SOW. I would not hesitate to recommend your services again.” Post Market Surveillance Manager, Innovative MedTech Company “Our regulatory affairs manager was a great support, offered great collaboration, and I appreciated his input into this project.” Regulatory Affairs Manager, Innovative MedTech Company “RQM+ offered incredible support throughout the project, and the engineer recommended was extremely well-trained and provided a ton of value to the project!” Sr. Manager Supplier Quality Engineering, Innovative MedTech Company “I have recommended RQM+ to others and will continue to do so, and RQM+ will be the first place I turn if the need for external support arises. I depend on the support I receive from RQM+ and I trust the guidance provided to me by their expert staff.” RA Lead, Innovative MedTech Company “I appreciate the support provided by RQM+ and the dedication to our projects, as well as kind and efficient communication and RQM+ availability whenever there is such a need. Thank you!” Medical Director, Innovative MedTech Company “Absolutely a 10 for our clinical research lead. My organization is stronger thanks to her support and expertise.” Director, Clinical Research & Scientific Affairs, Innovative MedTech Company “Our regulatory specialist is a great support, with great collaboration and discussion. I appreciate his input into our projects.” Regulatory Affairs Manager, Innovative MedTech Company “Our regulatory specialist and entire RQM+ team have been very pleasant to work with and are very knowledgeable and have provided great support with our clinical documentation for EU MDR.” Regulatory Affairs Specialist, Innovative MedTech Company “Our design quality expert has provided excellent support. His knowledge of medical devices and regulations is very good and he takes on difficult tasks with little guidance needed.” Sr Manager, Design Quality Assurance, Innovative MedTech Company “As always, it is a pleasure to work with the RQM+ team. They have very knowledgeable and professional; I greatly appreciate your support!” VP of Quality, Global Medical Device Manufacturer “Our project lead's team continues to provide great support for our PMS documents, they are very well organized and on track for all deliverables related to this project.” PMS Specialist, Innovative MedTech Company “An absolute 10. RQM+ has provided invaluable support that has made a huge impact to our team and bottom line.” PMS Specialist, Innovative MedTech Company The Latest From RQM+ #### In Vitro Diagnostics RQM+ provides deep regulatory and clinical expertise for in vitro diagnostic (IVD) manufacturers, with fully integrated support across EU IVDR and U.S. FDA requirements. From strategic planning through post-market performance follow-up (PMPF), our MedTech-only team helps de-risk development, accelerate submissions, and support global market success.  Start Now  Why RQM+ for IVDs? Standards We Navigate EU IVDR (Regulation EU 2017/746) ISO 13485 – Quality Management Systems for Medical Devices ISO 15189 – Medical Laboratories – Requirements for Quality and Competence ISO 20916 – Clinical Performance Studies of IVDs FDA 21 CFR Parts 11, 50, 56, 58, 807, 809, 812, 820 CLSI EP Series Guidelines (e.g., EP05, EP07, EP09) GDPR and IVDR Article 61 – Data protection in EU clinical research IVD Support Across the Total Product Life Cycle Expand each to see key services. 1. Design Concept Regulatory (US/EU) Intended use statement refinement (US: 510(k), De Novo, PMA / EU: IVDR classification A–D)  Regulatory pathway determination  Companion diagnostic vs. standalone diagnostic determination  Risk classification analysis under IVDR and FDA guidance  Jurisdiction and technology type assessment (e.g., NGS, PCR, antigen-based)  Quality QMS planning (ISO 13485, IVDR-specific requirements)  Design control strategy  Risk management framework aligned to IVD-specific hazards  Supplier evaluation and selection planning  Clinical Analytical vs. clinical performance study planning  Early clinical evidence generation roadmap  Companion diagnostic biomarker validation requirements  Reimbursement Coverage landscape for diagnostic category  Coding and payment feasibility assessment (CPT/PLA/HCPCS in US)  HTA and evidence expectations (EU)  Preliminary value proposition outline  Medical Writing Regulatory strategy brief  Preliminary Intended Use and claims language  Value proposition outline  Development of initial analytical/clinical performance plans  2. Design & Development Regulatory (US/EU) FDA pre-submission package (e.g., Q-Sub, IDE)  EU Scientific Advice engagement  Labeling and IFU content guidance  Classification and grouping strategy under IVDR  Software as part of IVD (SaMD) pathway alignment  Quality Design History File (DHF) preparation  Traceability matrix from requirements to testing  Risk management file development  Supplier quality documentation  Reagent manufacturing control documentation  Clinical Clinical performance study design (e.g., prospective, retrospective, bridging)  Analytical protocol development (sensitivity, specificity, LoD, etc.)  Comparator selection and justification  Site/investigator alignment  Reimbursement Evidence strategy development for payers and HTA  Clinical utility study planning  Economic modeling inputs  Strategy for obtaining proprietary codes or PLA codes  Medical Writing Protocol writing (analytical and clinical)  Labeling and IFU content  Drafting risk-benefit narrative  Early technical documentation for IVDR  3. Verification & Validation Regulatory (US/EU) Analytical validation summary documentation support  FDA alignment for LoD/LoQ studies  EU verification report preparation per IVDR Annex II  GSPR mapping  Quality Verification & validation test protocol support  Documentation for analytical software testing (for software-enabled IVDs)  Risk file finalization  Support for verification method documentation  Clinical Clinical performance study execution support  Comparator analysis documentation  Sample size justification and statistical plan validation  Reimbursement Aligning performance claims with economic messaging  Demonstrating clinical relevance of endpoints for payer acceptance  Medical Writing Analytical and clinical validation summary reports  Study protocol amendments  CER performance summary  Labeling refinements  4. Clinical Evidence Generation Regulatory (US/EU) Clinical performance study management support  Support for IDEs (US) and Clinical Performance Study Applications (EU)  Clinical trial compliance documentation  Consent and ethics review documents  Quality Monitoring SOPs and GCP compliance  Clinical site quality documentation  Data integrity controls for sample tracking  Clinical Full-service clinical trial execution  Data management and statistical analysis  Interim analyses and enrollment tracking  Study site monitoring  Reimbursement HTA dossier input strategy (EU)  Integration of clinical evidence with payer-required outcomes  Planning for post-trial economic modeling  Medical Writing Clinical performance protocols  Informed Consent Forms (ICFs)  Interim and final Clinical Study Reports (CSRs)  Patient narratives or case reports (if needed) 5. Manufacturing Readiness Regulatory (US/EU) Labeling and UDI prep  Country-specific registration planning  Instructions for Use (IFU) finalized per IVDR Annex I  Quality QMS implementation (ISO 13485, IVDR Annex IX)  Manufacturing process documentation  Supplier audit documentation  CAPA system and field readiness processes  Clinical PMPF planning (EU)  Stability studies for performance impact  Reimbursement Alignment of launch label with payer-relevant claims  Launch price justification documentation  US: coding and coverage planning  Medical Writing Final Instructions for Use (IFU)  Launch-ready GSPR checklists  PMPF plan write-up  Labeling for global submissions  6. Regulatory Submissions Regulatory (US/EU) FDA: 510(k), De Novo, PMA or Dual 510(k)/CLIA submissions  EU: IVDR Technical Documentation (Annexes I, II, III, IX)  GSPR crosswalk development  IFU and UDI compliance  Quality DHF/DMR audit-ready review  SOP readiness  Final traceability documentation  Clinical Final CER with analytical and clinical evidence  Summary of Safety and Performance (SSP)  Performance claims substantiation  Reimbursement Reimbursement strategy integration into submission  HTA document coordination  Pre-sub alignment with CMS (US) or HTA (EU)  Medical Writing Submission module writing (FDA/IVDR)  CER and SSP writing and formatting  Deficiency response letters  Labeling narrative summaries 7. Market Access & Launch Regulatory (US/EU) Registration execution (FDA, EU NB, global)  UDI and EUDAMED support  Country labeling variations  Quality Complaint handling SOPs  Surveillance process documentation  Notified body / competent authority audit prep  Clinical PMPF study initiation  RWE program planning  Reimbursement Reimbursement code submission  Engagement with HTA bodies  Development of launch market dossiers  Medical Writing PMPF protocols  Launch support materials for access teams  Health economics summaries  Payer education content  8. Post-Market Activities Regulatory (US/EU) PMS reports, PSURs, PMPF Reports (EU)  Vigilance and adverse event reporting  CAPA regulatory support  Quality Audit support and system monitoring  Complaint investigations  Change control documentation  Clinical:  PMPF execution and analysis  RWE capture strategy  Registry participation (if applicable)  Reimbursement Evidence updates to support continued reimbursement  Annual review of coverage and payer support tools  Troubleshooting batch variation  Medical Writing PSURs and PMPF reports  RWE summaries  CER updates  Surveillance narrative reports  9. Design Changes, M&A, & Market Expansion Regulatory (US/EU) EU: Substantial Modification review under IVDR  US: Special/Panel-track supplement strategy  Global regulatory expansion support  Quality QMS integration for acquired products  Risk file and DHF updates  Updated training documentation  Clinical Clinical bridging study planning  CER updates  Label expansion justification  Reimbursement Global pricing strategy  New indication value messaging  Expansion of economic modeling  Medical Writing Revised IFUs and labeling  Updated CERs  M&A transition documentation  10. Emergency Support Regulatory (US/EU) Notified body non-conformance response  FDA 483/Warning Letter remediation  Rapid audit preparation  Quality Emergency SOP development  Field action documentation  Quality system triage support  Clinical Clinical investigation remediation  CAPA and study redesign  Post-market corrective study support  Reimbursement Crisis coverage reevaluation support  Engagement with CMS/HTA to mitigate disruption  Medical Writing Emergency update of CERs/SSPs  CAPA narratives and NB responses  Clinical risk assessment documentation  Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Lab & Material Science When speed and quality are paramount, you need a partner who delivers results you can trust. At RQM+, we specialize in comprehensive analytical lab and material science tailored to meet the needs of medical devices, pharmaceuticals, consumer products, and polymers. Jordi Labs, an RQM+ company, is recognized by the FDA as the gold standard in chemical characterization and extractables and leachables (E&L) testing, providing critical insights that ensure product safety and regulatory compliance.  With 40+ years of experience, we turn complexity into clarity — delivering faster timelines than industry norms and pricing that keeps you ahead. Start Now  Our Core Lab Services Jordi Labs services are designed to address your unique challenges: Chemical Characterization Extractables and leachables (E&L) analysis, polymer deformulation, unknown identification and contaminant investigations Biological Evaluation Biocompatibility assessments and toxicological risk evaluations to meet ISO 10993 requirements Investigative Testing Identify unexpected contaminants, degradation pathways, or unknown compounds. Resolve complex chemical and materials issues. Toxicology Expert toxicological assessments for biocompatibility, E&L, and impurity analysis. Supporting risk evaluations and regulatory submissions across product classes. Regulatory Submission Support Expert documentation to streamline approval processes with the FDA and notified bodies Failure Analysis Comprehensive investigations to identify root causes and provide actionable insights Extractables & Leachables Ensure patient safety and global compliance with targeted E&L studies. Precise identification for your product and material type. Key Benefits Partnering with RQM+ delivers:  Explore Jordi Labs' Analytical Expertise Jordi Labs' Demonstrated Expertise  Trusted by leading medical device and pharmaceutical companies around the world  FDA-recognized E&L methods are frequently cited in regulatory guidance documents  Extensive expertise in ISO 10993 biocompatibility testing  “The report provided was excellent. Clear, well-outlined, and exactly what we were hoping for. We're very pleased with the quality and professionalism of the work done.” Manager of Product Development, Innovative MedTech Company “Thank you so much for quickly completing the testing and report. I was able to confidently present results at my internal meeting. Your team's promptness really saved the day!” Senior Scientist, Innovative MedTech Company “We were thrilled with the quick turnaround of our latest report and the clarity of the results. Your team's responsiveness continues to impress, especially when we've needed additional insights.” Quality Assurance Lead, Innovative MedTech Company “The testing insights provided went above and beyond our expectations. Your report thoroughly answered our questions, was insightful, and the speed at which you delivered was impressive.” Director of Regulatory Affairs, Innovative MedTech Company “Your analysis was spot-on and provided precisely the clarity we needed. As always, your dedication to accuracy and detail stands out. Fantastic job!” Principal Scientist, Innovative MedTech Company “I'd like to take this opportunity to say thank you for your support and commitment to this project. Your support made so much of this project possible.” Director of Operations, Innovative MedTech Company “Your team's fast response and consistent reliability always impress us. Thanks for the excellent service - we genuinely appreciate your commitment!” Program Manager, Innovative MedTech Company Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Leadership We believe leadership is about more than titles. At RQM+, it’s all about evolving MedTech. Our executive team combines industry expertise, clinical know-how, and a passion for patient outcomes to lead RQM+ and our clients toward success. With decades of combined experience across clinical trials, regulatory and quality, lab services, and reimbursement, our leaders ensure that we remain at the forefront of the MedTech industry.  #### Make MedTech Happen MedTech is evolving — and so are we. RQM+ has long been your go-to partner for regulatory, quality, and compliance. That hasn’t changed. What’s changed is how much more we can do to support you today. As The MedTech CRO, we offer integrated clinical, regulatory, quality, and lab services — helping you accelerate development, reduce risk, and achieve global success. From startups to global manufacturers, we’re built to scale with your needs and simplify the most complex challenges. Legacy expertise. Expanded capabilities. Continued commitment to your success. Explore how RQM+ is redefining what a MedTech Contract Research Organization can do. Let’s Make Your MedTech Happen Access Device-Specific Expertise Whatever your MedTech area of need, we’ve got you covered. Discover our expertise for your product type:   Why RQM+? As The MedTech CRO, we deliver comprehensive, MedTech-specific solutions that help you bring life-changing innovations to market faster. Here’s how:  End-to-end MedTech expertise  We offer comprehensive services across the entire MedTech product lifecycle, from regulatory strategy and quality assurance to clinical trials, materials testing, and reimbursement — even post-market clinical follow-ups (PMCF). MedTech is all we do. Insider regulatory knowledge Our team consists of former FDA, MHRA, and notified body leaders; they understand regulatory processes from the inside. This expertise helps us anticipate your challenges, reduce your delays, and accelerate your approvals. Proven results across all products We bring deep expertise across medical devices, in vitro diagnostics, companion diagnostics, software-enabled products, and combination products to projects. Our solutions cover everything from pre-clinical development to post-market support, so no matter where you are in the process, we’ve got you. Tech-enabled solutions Leveraging technology and human expertise enables us to solve complex MedTech challenges faster with more strategic, insight-driven solutions. By combining advanced tools with deep expertise, we streamline regulatory processes and other critical functions, accelerating innovation. A partner for all MedTech companies Whether you’re a budding startup or a global leader, we tailor our solutions to meet your needs in every project. We even offer specialized support to growing companies to help overcome resource challenges and bring products to market.  Business-balanced approach Our strategies don’t just focus on compliance — we help you achieve regulatory success while meeting your commercial goals. We synergize regulatory strategy, reimbursement planning, and business priorities to ensure your innovations reach patients efficiently and effectively. “The talent, expertise, and professionalism with RQM+ sets them above the other vendors I have worked with in the past. We have developed a great relationship and it has been a pleasure to work with RQM+. Thank you.” Senior Manager, Quality Assurance, Innovative MedTech Company “Very happy with our working relationship and have plenty more projects lined up and ready to start.” Director, Clinical Affairs, Global Medical Device Manufacturer Integrated, End-to-End MedTech Solutions Our solutions are powered by tailored expertise across four core service areas to advance your MedTech product from concept to market:  Proven Track Record of Success We’ve worked with 19 of the top 20 medical device companies and 7 of the top 10 IVD companies, delivering transformative solutions across the MedTech product life cycle.  1,000+ Clients Served 5,000+ Completed Projects 1,300+ Studies Over 100 20+ Year Industry Veterans Through industry-leading experts and integrated solutions in areas that are key to your product’s success, we make innovative products happen for MedTech companies around the world.  Hear From Our Customers “I am amazed at how much work and the number of decisions that have been made to date on this project! I really appreciate the effort and patience of your entire team!” Director, Regulatory Affairs, Global Medical Device and Diagnostics Manufacturer #### Market Access Roadmap Achieving market access and reimbursement for your MedTech product is a process with multiple steps. At RQM+, we specialize in creating tailored market access road maps that address your product’s regulatory, reimbursement, and commercialization challenges.   We integrate actionable insights and strategic planning to ensure your innovations reach patients faster, safer, better.  Start Now  Benefits of RQM+ Reimbursement Strategy Services Core Market Access Road Map Services Our market access and reimbursement solutions include: Regulatory and Reimbursement Integration Aligning regulatory approval processes with reimbursement planning to ensure smooth transitions from development to market  Customized strategies for coding, coverage, and payment to optimize access Market Entry Planning In-depth analyses of payer landscapes, market dynamics, and patient populations  Identifying barriers based on clinical indications, place of service, and payer mix Payer Engagement Strategies Developing clinical dossiers and evidence-based advocacy materials  Building relationships with key stakeholders, including private payers, CMS, and medical specialty societies Data-Driven Decision Support Leveraging informatics and data analytics to refine market positioning and pricing strategies  Providing actionable insights for global launch planning and competitive benchmarking  Making It Happen for Our MedTech Partners  Partnered with top 20 MedTech companies to develop successful market access strategies  Secured coding and reimbursement solutions for emerging medical technologies, enabling faster adoption  Supported clients in advocating for expanded coverage through payer engagement and evidence-based materials  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  #### Match with a Contractor Match with a MedTech contractor who fits your needs, timeline, and budget. How it works: 1. Answer the questions below in five minutes or less.2. Your information triggers an automated database search across thousands of qualified MedTech professionals.3. Matches are delivered to you via email and if any fine tuning is required, we'll ask additional questions. Let’s Make Your MedTech Happen #### Med Device The path to bringing new medical devices to market is filled with regulatory hurdles, technical challenges, and market access nuances. At RQM+, we amass decades of expertise across regulatory and quality, clinical trials, lab & material science, and reimbursement strategies to help your product succeed at every stage of its life cycle.   From innovative product development to post-market surveillance (PMS), we have the tools and experience to make your MedTech happen.  Start Now  Medical Device Consulting Benefits Why partner with RQM+ for your clinical trial consulting and management needs? Let’s count the ways:  MDR Planning and Execution The European Union’s Medical Device Regulation (MDR) has redefined compliance standards for MedTech companies. This can pose challenges for manufacturers worldwide. RQM+ simplifies this process, offering industry-leading guidance to ensure your products meet MDR requirements efficiently and effectively.  Our MDR Expertise Includes: Technical documentation Comprehensive gap analysis and remediation of technical files to meet MDR standards Clinical evaluation reporting (CER) Developing robust CERs aligned with MDR Article 61 and Annex XIV requirements Post-market surveillance Strategies for MDR-compliant PMS plans, reports, and periodic safety updates (PSURs) Notified body engagement Expertise in preparing and managing submissions to notified bodies “We've recently received MDR certification thanks in large part to the guidance provided by the RQM+ team. Their expertise and availability have been instrumental in helping us to achieve this major milestone.” Director Global Regulatory Affairs, Global Medical Device Manufacturer “RQM+ was great to work with on this project, and the project lead provided exceptional support throughout.” Vice President Clinical Affairs and Project Management, Innovative MedTech Company “RQM was able to meet our needs and assist us during the CER support project. We appreciated the quality of the service, project follow-up and communication.” Senior Regulatory Affairs Specialist, Global Medical Device Manufacturer “Excellent work by a highly skilled and professional team of project manager (our regulatory specialist) and clinical-regulatory scientist/experts working within the agreed timelines and therefore resulting in high quality CER literature refresh.” Director of Clinical Research, Innovative MedTech Company “We were appreciative of the support the RQM+ team supplied assisting us with completing our CER.” Director of Quality & Regulatory Affairs, Global Medical Device Manufacturer Core Services for Medical Devices Consulting Tailored regulatory strategies for navigating U.S., EU, and global markets  Comprehensive remediation support for FDA warning letters, consent decrees, and global audits  Clinical Trials Pilot, pivotal, and post-market clinical trials designed to meet regulatory and payer expectations  Expertise in trial design, site activation, and biostatistics   Clinical Trials Overview Failure Analysis Root cause investigations for medical device and polymer material failures Detailed analysis of mechanical, chemical, and thermal degradation Actionable findings to inform CAPA and improve product performance and reliability  Lab & Material Science Extractables and leachables (E&L) testing, polymer analysis, and ISO 10993 compliance  Innovative solutions for investigating material failures and contamination issues  Lab & Material Science Overview Reimbursement Coding, coverage, and payment strategies tailored for medical devices   Health economic analyses to demonstrate value and secure market access Reimbursement Overview #### Media Inquiries Are you a member of the media looking to speak with an RQM+ representative? Our global media relations team is here to assist with your inquiries about our services, expertise, and insights into the evolving MedTech landscape.  Complete the form below, and a member of our team will get back to you promptly.  Media Contact Form #### Medical Device At RQM+, our medical device testing services provide the expertise, technology, and regulatory support to overcome even your most daunting challenges. From extractables and leachables (E&L) analysis to post-market surveillance, we offer comprehensive solutions to accelerate your product’s path to market.   With over 40 years of experience, our gold standard testing methods (via Jordi Labs, an RQM+ company) are trusted globally, ensuring your devices meet and exceed the highest regulatory requirements.  Start Now  Your Gold Standard Medical Device Testing Benefits When you partner with RQM+ for MedTech device testing, you gain:  Core Medical Device Testing Services Our analytical lab services for medical devices include: Extractables and Leachables (E&L) Testing Comprehensive assessments for regulatory requirements  Proprietary coverage-based methods for accurate identification and quantification  Deep know-how to support FDA and global regulatory submissions  Material Characterization and Deformulation Advanced analysis of polymers, additives, and contaminants  Failure investigations and quality control solutions  PFAS testing services  ISO 10993 Biocompatibility Testing Comprehensive testing and risk assessments for global market approval  Tailored support to speed your trek through complex regulatory pathways  Guidance on toxicological risk assessments and material selection  Delivering Real Results  Our focused, client-centric approach and deep pool of experienced team members — including former regulators — put you in a prime position to succeed:  Supported regulatory submissions for top global medical device manufacturers  Proprietary methods frequently cited in scientific and regulatory guidance  Equipped with cutting-edge technologies, including advanced spectrometry and chromatography  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  Medical Device Testing Services Made Easy  Your medical device deserves the best support to ensure safety, compliance, and market success. With RQM+, you gain industry-leading expertise and a globally trusted partner to guide you toward success every step of the way.  #### Medical Devices RQM+ provides deep regulatory, quality, clinical, testing, and reimbursement expertise across the entire life cycle of medical devices from early concept development to post-market surveillance. Whether you’re launching a novel device, expanding into new geographies, or addressing complex regulatory requirements in the U.S., EU, or globally, our MedTech-only team offers tailored solutions to de-risk development, accelerate submission, and support global market access. Start Now  Why RQM+ for Medical Devices? Therapeutic Expertise Cardiology Oncology Neurology Women's Health Orthopedics General Surgery Wound Care Urology Ophthalmology Infectious Disease Spine Life Cycle Support Highlights Expand each to see key services. 1. Design Concept Regulatory (US/EU) Regulatory strategy development  Intended use and indication refinement  Jurisdiction and classification (e.g., 510(k), PMA, EU MDR Rule-based)  Predicate/reference product analysis  Risk-based regulatory pathway assessment  Quality QMS planning (ISO 13485)  Supplier qualification strategy  Risk management framework planning (ISO 14971)  Design control planning documentation  Early traceability matrix structure  Clinical Early clinical development strategy  Endpoint identification for feasibility  Usability and human factors study planning (IEC 62366)  Reimbursement Payer landscape and evidence expectations (CMS, HTA bodies)  Value proposition development  Coding pathway research (US)  EU market access early input  Labs (Jordi Labs) Preliminary materials compatibility review  Biocompatibility risk assessment  Extraction methodology planning (ISO 10993-1)  Toxicological strategy  Medical Writing Regulatory strategy write-up  Intended use statement development  Clinical development plan summary  Value dossier framework draft  2. Design & Development Regulatory (US/EU) FDA Pre-Sub / Q-Sub support  EU Scientific Advice support  Design dossier regulatory reviews  Drafting device descriptions for regulatory filing  Quality Design History File (DHF) documentation  Traceability matrix and design input/output tracking  Software development life cycle documentation (IEC 62304)  Supplier quality documentation  Risk file construction  Clinical Study protocol design (feasibility or pivotal)  Site engagement and investigator identification  Human factors formative testing planning  Reimbursement Economic model input documentation  Stakeholder engagement prep (payers, HTA)  Coding/coverage feasibility  Pricing planning for target markets  Labs (Jordi Labs) Extraction testing protocol review  Chemical characterization planning  Batch-to-batch comparison testing strategies  Medical Writing Protocol writing  Investigator Brochure (IB) drafting  Risk-benefit summaries  IFU and product description writing 3. Verification & Validation Regulatory (US/EU) Test method documentation alignment with regulatory expectations  Human factors validation support documentation  FDA pre-sub for validation review  EU verification reports and risk file updates  Quality Support for test method validation documentation  Risk file closure  Compliance review of V&V protocols (IQ/OQ/PQ)  Final DHF/DMR compliance package  Clinical Human factors summative testing  Usability validation  Device handling and use validation documentation  Reimbursement Validation of outcomes-based value messaging  Clinical value alignment to payer strategy  Labs (Jordi Labs) ISO 10993 panel execution documentation support  Extractables & Leachables study design  Toxicological risk assessments  Material certificates and conformance review  Medical Writing Validation summary reports  Clinical validation evidence reports  Labeling support documentation  Final usability documentation  4. Clinical Evidence Generation Regulatory (US/EU) IDE (US) or Clinical Investigation Application (EU) preparation  Clinical trial regulatory compliance  Site and sponsor documentation preparation  Quality GCP compliance documentation  SOP development for monitoring and data handling  Clinical quality management plan  Clinical Full-service trial execution (monitoring, data collection, biostatistics)  Study site training and oversight  Clinical Study Reports (CSR)  Reimbursement Evidence development aligned with coverage expectations  Early payer discussions (US)  HTA evidence dossier strategy (EU)  Labs (Jordi Labs) Clinical use batch testing  Study product E&L review  Shelf-life testing  Medical Writing Clinical Protocols and Amendments  Informed Consent Forms (ICFs)  Clinical Study Reports (CSRs)  Investigator Brochures  Interim analysis summaries  5. Manufacturing Readiness Regulatory (US/EU) Device description finalization  IFU and UDI guidance  Country-specific registration strategy  Quality QMS implementation (ISO 13485, MDSAP prep)  Internal audit support  Supplier audit documentation  CAPA system readiness  Process validation documentation (support only)  Clinical PMCF plan (EU)  Clinical data use in manufacturing documentation  Reimbursement Labeling review to support coverage strategy  Finalization of payer messaging  Labs (Jordi Labs) Final materials testing and compliance  Packaging and shelf-life testing  Medical Writing UDI label content  Instructions for Use (IFUs)  PMCF plan narrative  Technical File content  6. Regulatory Submissions Regulatory (US/EU) FDA: 510(k), De Novo, PMA submissions & exemptions  EU MDR: Technical Documentation for NB review  Global registration document preparation  Deficiency response drafting  Quality Risk file updates  Audit prep documentation  Inspection readiness materials  Clinical Clinical Evaluation Report (CER)  Summary of Safety and Clinical Performance (SSCP)  Trial results summaries  Reimbursement Coverage and reimbursement support within submission  Value story alignment with submission strategy  Labs (Jordi Labs) Biocompatibility reports  Shelf-life data  Final material declarations  Medical Writing Submission module writing (FDA/CE)  GSPR cross-reference tables  Executive summaries for submissions  Deficiency response narratives Regulatory & Quality Overview 7. Market Access & Launch Regulatory (US/EU) UDI and EUDAMED submission  Final IFU, label, and country-specific approvals  Global registration execution  Quality Field action readiness  Complaint handling SOPs  Post-market audit support  Clinical PMCF study launch  Real-world data tracking plans  Registries integration  Reimbursement HTA engagement (EU)  Coverage and coding submissions (CMS/payers)  Launch toolkit development  Labs (Jordi Labs) Launch batch verification  Final packaging validation (documentation only)  Medical Writing PMCF protocol and plan  Launch content for field teams  HTA briefing book  Patient-facing educational content  8. Post-Market Activities Regulatory (US/EU) PSUR, PMS Reports (EU)  MDR, Vigilance Reporting (US)  PMCF Reporting  Quality CAPA execution  Surveillance system updates  Periodic internal audits  Clinical PMCF data collection  RWE strategy and study execution  Registry engagement and analysis  Reimbursement Real-world outcomes reporting  Coverage renewal support  Labs (Jordi Labs) Ongoing testing for materials/complaints  Root cause support testing  Medical Writing PSUR, PMS, PMCF Reports  RWE summary briefs  Post-market analysis and updates  9. Design Changes, M&A, & Market Expansion Regulatory (US/EU) Change notification strategy (FDA supplements, EU Substantial Changes)  Regulatory impact assessments  International expansion registration  Quality System harmonization  Risk file and DMR updates  Training program documentation  Clinical Bridging studies and comparative studies  PMCF updates  Reimbursement Value messaging updates for new claims  Pricing strategy updates for new geographies  Labs (Jordi Labs) New material characterization  Equivalence analysis  Medical Writing Change impact summary  Updated IFUs and CERs  Submission module updates  10. Emergency Support Regulatory (US/EU) 483 / Warning Letter response strategy  Notified body audit findings remediation  Regulatory crisis management  Quality Emergency audit prep  SOP development and QMS corrections  Field safety corrective action documentation  Clinical Clinical hold remediation  Urgent study redesign  Unplanned PMCF needs  Reimbursement Crisis-based payer messaging  Coverage re-engagement  Labs (Jordi Labs) Root cause failure testing  Rapid tox reanalysis  Medical Writing Emergency response narratives  CAPA documentation  Rapid CER/SSCP updates  Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### New Product Development RQM+ is your single stop for IVD, combination product, and medical device development consulting services. Our regulatory, quality, clinical, and reimbursement consulting help transform your innovative ideas into market-ready products. With decades of experience, we understand the ins and outs of new product development. We guide you through the process so you can take your device from initial concept to global market release.  It doesn’t matter whether you’re a small company designing a cutting-edge diagnostic or a large company developing a new auto-injector. We’re here to make MedTech happen for you — faster, safer, better.  Start Now  Comprehensive Product Compliance Support At RQM+, we go beyond standard regulatory frameworks to ensure your product is compliant across all critical global regulations. We cover:  Regulatory Essentials QMSR, EU MDR, IVDR, and ISO 13485 Artificial Intelligence Act Compliance for AI-driven medical technologies Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) Ensuring product safety and environmental sustainability Battery Regulation Supporting MedTech devices with integrated battery systems Packaging and Packaging Waste Regulation (PPWR) Sustainable packaging compliance for global markets Key New Product Development Benefits When you collaborate with RQM+, you receive benefits that directly impact your product’s success and improve patient outcomes:  Core Medical Device Development Consulting Services We provide comprehensive services tailored to ensure your product’s success, including:  Regulatory Strategy & Submissions  FDA submissions:   510(k) Premarket Notifications  De Novo Applications  Premarket Approvals (PMAs)  Emergency Use Authorization (EUA)  Request for Designations (RFDs)  Pre-Submission (Q-Sub)  Investigational Device Exemptions (IDEs)   Breakthrough Designation Requests  Humanitarian Use Device (HUD)  Safer Technologies Program (SteP)   Request for Information (513(g))  Drug-Device Combination Products (IND, NDA, ANDA, BLA – Device portion only)  CE marking and MDR/IVDR compliance  Regulatory pathway analysis and strategic planning  Worldwide regulatory strategies  Submission review (U.S. or EU)  Refuse to accept or hold letter support  Acquisition due diligence review  Biological evaluation plans/reports  Change impact assessments  Marketing and labeling review  Registrations and listings  Reimbursement strategies and approvals  Design Assurance & Technical Documentation Support  Development of Design History Files (DHF) and technical documentation  Risk management plans and safety analyses  Verification/validation (V&V) support  Manufacturing and supplier quality  Global Market Navigation Expertise in U.S., EU, U.K., Canadian, and APAC regulatory frameworks  Integrated support for combination products and IVDs  Ongoing collaboration with notified bodies in the EU and the FDA in the U.S.  Quality Management System (Support)  QMS development  QMS audits  Clinical Trial Support Literature searches and clinical strategy  Clinical investigation plans/protocols  Draft study documents  Clinical study approval  History of Success Supported 19 of the top 20 medical device manufacturers  Over 40 years of regulatory consulting expertise  Proven success navigating U.S., EU, and U.K. regulatory landscapes  Recognized as leaders in design assurance and risk management Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  Therapeutic Area Expertise Our expertise extends to numerous therapeutic areas, including: Oncology Respiratory care General surgery Women’s health Infectious disease Orthopedics and spine Urology Neurology Wound care Ophthalmology Explore Our Expertise #### News URL: https://www.rqmplus.com/about-us/news-events/news/ #### News & Events At RQM+, we’re constantly evolving to better serve the MedTech industry. From participating in leading global conferences to sharing thought leadership insights, we stay on the forefront of innovation and regulatory guidance.   Upcoming Events RQM+ on LinkedIn Get actionable MedTech insights, regulatory updates, event information, career opportunities, and more by following RQM+ on LinkedIn. We release a LinkedIn-exclusive newsletter every week (subscribe here).  RQM+ News #### Order an Audit How it works: 1. Answer the questions below in five minutes or less.2. Select a calendar date and time to speak with us and move your audit forward. Let’s Make Your MedTech Happen #### Partner with Us We help MedTech companies overcome regulatory and quality, laboratory, clinical, and reimbursement challenges. With vast expertise, proven solutions, and a commitment to client success, we’re a reliable, flexible partner in bringing life-changing medical technologies to patients — faster, safer, better. Let’s Make Your MedTech Happen Submit the form below and our team will respond within 1–2 business days. Addresses and Phone Numbers United States HQ 5000 Centregreen WaySuite 100Cary, NC 27513United States (U.S.) +1 877 652 0830 EuropeHQ 3rd Floor, 1 Ashley RoadAltrincham, Cheshire, WA14 2DTUnited Kingdom (U.K.) +44 115 921 6200 Switzerland Office Grosspeter TowerGrosspeteranlage 294052 BaselSwitzerland +41 61 511 4930 United States Lab Jordi Labs, an RQM+ Company 200 Gilbert St.Mansfield, MA 02048United States (U.S.) +1 833 888-0224 Germany  Frankfurt Office Eschersheimer Landstraße 1460322 Frankfurt/MainGermany +49 23 82 987-44-0 Germany  AhlenOffice Von-Geismar-Straße 259229 AhlenGermany #### Payer Research & Gap Analysis The road to MedTech market access is paved with challenges. From understanding payer requirements to addressing gaps in coverage, when you partner with RQM+, you gain deep expertise in market access consulting and robust data analytics. With decades of client success stories, our payer research and gap analysis services provide the clarity and strategy you need to advance.   We uncover the barriers to reimbursement and chart a path forward to ensure your products reach patients rapidly and effectively.  Start Now  Payer Research and Gap Analysis Benefits When you partner with RQM+ for market access consulting, you gain:  Core Payer Research and Gap Analysis Services Our payer research and gap analysis services include:  Payer Landscape Evaluation Comprehensive assessment of government and private payer policies  Identification of clinical and policy gaps that impact reimbursement eligibility Reimbursement Gap Analysis Evaluation of coding, coverage, and payment gaps across payer systems  Recommendations to align clinical evidence with payer expectations Stakeholder Engagement Strategies Development of targeted advocacy materials to address payer concerns  Facilitation of discussions with policymakers, medical societies, and private payers Data-Driven Decision Support Advanced analytics to assess policy trends and reimbursement risks  Insights you can use to improve product positioning and market entry How We’ve Supported Our MedTech Partners   Supported clients in securing coding and coverage for innovative medical devices using proven payer advocacy strategies  Delivered detailed payer landscape analyses that enabled optimized reimbursement pathways for global MedTech companies  Developed gap analysis reports that informed successful market access plans and timely product launches  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  #### Pharmaceutical In the pharmaceutical industry, precision and compliance are nonnegotiable. RQM+ specializes in pharmaceutical testing lab services designed to ensure your drug products meet regulatory standards. From extractables and leachables (E&L) testing to impurity analysis and contamination investigations, we provide the expertise and technology to help you achieve market readiness. Trusted by leading pharmaceutical manufacturers, we turn complexity into clarity with data you can trust and insights you can implement. Start Now  Your Pharmaceutical Testing Benefits Partnering with RQM+ delivers: Core Pharmaceutical Testing Lab Services Our analytical lab services for pharmaceuticals include: Extractables and Leachables Testing Comprehensive E&L analysis to assess potential risks and ensure regulatory compliance for biologics, injectables, and other pharmaceutical products Impurity and Degradation Analysis Identification and characterization of impurities and degradation products to maintain product integrity and safety Contamination Investigations Advanced techniques to identify and resolve contamination issues quickly and effectively  Toxicological Risk Assessments Expert guidance on risk assessment strategies to ensure patient safety and regulatory approval Pharmaceutical Testing Done Right FDA-recognized methodologies frequently cited in regulatory guidance documents  Trusted by top pharmaceutical manufacturers for E&L testing and impurity analysis  Proven track record of delivering actionable data and ensuring timely market readiness Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  One Provider for All Your Pharmaceutical Lab Testing Needs Bringing pharmaceutical products to market efficiently requires the seamless integration of testing, compliance, and regulatory support. At RQM+, we deliver end-to-end solutions that cover every stage of the process — from initial formulation and material analysis to regulatory submissions and post-market monitoring.  We deliver the data and insights you need for regulatory success. With industry-leading expertise and cutting-edge technology, we help you navigate complex challenges and bring safe, effective products to market.  #### Pilot Studies Pilot studies are the cornerstone of successful medical device development, serving as a critical step in validating safety, efficacy, and feasibility. At RQM+, we specialize in medical device clinical trial design, delivering tailored pilot studies that align with your product’s unique needs.   Partner with us to mitigate risk, refine your pilot study design, and seamlessly transition to pivotal studies — all while securing quality data and patient safety.  Start Now  Why Choose Us for Pilot Studies? Partnering with RQM+ means:  Core Services for Medical Device Pilot Studies Medical Device Clinical Trial Design Early feasibility studies customized to your product’s lifecycle stage and target markets  Integrated Regulatory Strategy Aligning trials with U.S., EU, and global compliance standards   Streamlined Operations Efficient management of site strategy, activation, and operational execution  Data-Driven Decisions Collection and analysis of meaningful data to inform pivotal trials Let the Track Record Speak We know MedTech pilot studies because we:  Supported our partners’ pilot studies across diverse therapeutic areas, including cardiovascular, neurology, and oncology  Helped leading MedTech innovators successfully transition pilot studies into pivotal trials with regulatory precision  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  Proven Success Across MedTech  Your pilot trial should be the firm foundation for your MedTech success. With RQM+ as your trusted partner, you gain the expertise, guidance, and quality data needed to satisfy regulators and validate your product.  #### Pivotal Studies Pivotal studies are the defining stage in your product’s journey to market. At RQM+, we specialize in clinical trial consulting, designing, and managing pivotal studies that demonstrate safety, efficacy, and regulatory compliance for your product. With our deep MedTech expertise and a team stacked with former regulators, we ensure your trials are executed with precision.   RQM+ provides the evidence you need to gain market approval and make a meaningful impact on patient lives sooner.  Start Now  Why Choose RQM+ for Pivotal Studies? Customized solutions, global compliance expertise, and real-time insights to drive study success: Core Services for Pivotal Studies End-to-end support to ensure your pivotal studies deliver high-quality, regulatory-ready data:  Trial design and planning Custom trial protocols that address safety, efficacy, and compliance requirements across global markets Integrated regulatory strategy Trials aligned with U.S., EU, and global compliance standards Site strategy and activation Efficient site management and rapid activation Data quality and reporting Focus on robust data collection and analysis Results Are Essential How we’ve supported our partners in pivotal studies:  Completed pivotal studies resulting in timely regulatory approvals for a range of MedTech innovations Delivered robust trial outcomes across diverse therapeutic areas, including oncology, neurology, and cardiology  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  Your Resource for Clinical Trial Management Your pivotal study is more than a regulatory requirement; it’s a gateway to delivering life-changing innovations to patients. With RQM+, you gain a trusted partner committed to your success at every stage.  #### Please confirm your opt in below! Submit your email to receive free and exclusive RQM+ content, including blogs, white papers, and invitations to our panel discussions and webinars. Get MedTech insights straight to your inbox #### Privacy Notice INTRODUCTION RQM+ and its subsidiaries (“We,” “Us”) is committed to processing your data securely and transparently. This Privacy Notice sets out the types of data that we collect and hold on you as a client, potential client, or employee of the company. It also sets out how we use that information, how long we keep it for and other relevant information about your data.  RQM+ is aware of its obligations to residents and citizens of the EU under the General Data Protection Regulation (GDPR), of the UK under the Data Protection Act (UKDPA) and the (UK GDPR), of the Swiss Federal Act on Data Protection (FADP) and of the USA under a variety of legislation and acts that include data protection requirements – specifically including the California Consumer Privacy Act (CCPA), and the data protection requirements of residents and citizens of other countries, This Privacy Notice complies with the requirements of the above laws and regulations and is applicable globally but may be supplemented by additional information on our privacy practices that may be provided as required by applicable laws and regulations via notices provided at the time of data collection. Together, these are referred to as “Data Protection Legislation.”  RQM+ ACTING AS A DATA PROCESSOR When RQM+ is acting as a data processor, meaning that they handle personal data only on behalf of and under the instructions of a data controller, they do not decide why or how the data is used; they simply carry out the controller’s directives, such as storing, organizing, or analyzing the data under a clear contract. In this case the privacy regulations differ from those of a data controller. The link below outlines RQM+ responsibilities when acting in the capacity as a data processor.  RQM+ ACTING AS A DATA PROCESSOR  RQM+ ACTING AS A DATA CONTROLLER RQM+ is acting as a data controller, meaning that it determines the processes to be used when using your personal data. The company has appointed Data Protection Officer who is responsible for ensuring your data is stored and processed in accordance with this Privacy Notice. The Data Protection Officer can be contacted at dpo@rqmplus.com.   SCOPE This Privacy Notice applies to personal data that we collect and process in our capacity as a data controller through:  Our websites Our applications Our services Any other means through which we communicate with individuals LEGAL BASIS FOR PROCESSING We only process personal data when we have a lawful basis to do so under Article 6 of the GDPR. Depending on the context, our processing may be justified by one or more of the following legal bases:  Consent (Article 6(1)(a)): You have given clear consent for us to process your personal data for a specific purpose.  Contract (Article 6(1)(b)): Processing is necessary for the performance of a contract with you or to take steps before entering into such a contract.  Legal Obligation (Article 6(1)(c)): Processing is necessary for compliance with a legal obligation to which we are subject.  Legitimate Interests (Article 6(1)(f)): Processing is necessary for our legitimate interests (or those of a third party), unless overridden by your interests or fundamental rights and freedoms.  In relation to your personal data, we will:  process it fairly, lawfully and in a clear, transparent way  collect your data only for reasons that we find proper for the course of your relationship with RQM+ in ways that have been explained to you  only use it in the way that we have told you about  ensure it is correct and up to date  keep your data for only as long as we need it  process it in a way that ensures it will not be used for anything that you are not aware of or have consented to (as appropriate), lost or destroyed.  TYPES OF DATA WE PROCESS We may hold many types of data about you, including:  your personal details including your name, address, e-mail address, phone numbers  job title and job descriptions  job responsibilities  employer (and previous employers if known)  who you report to  your location  country that you reside in  information accessed and downloaded from company websites  events attended and met with RQM+ representatives  records of your contact with RQM+  marketing material and campaigns in which you have shown an interest.  We do not request, hold, or process special categories of data (such health, sexual orientation, race, ethnic origin, political opinion, religion, trade union membership, and genetic and biometric data) or criminal conviction data for clients or potential clients.  HOW WE COLLECT AND YOUR DATA We collect data about you in a variety of ways, and we would normally collect the data from you directly. This will usually start when you contact us or talk to us about a business need you or your company has but can also be when you have provided your details to access and download information from our website or shown an interest in specific topics of a marketing campaign. Further information may be collected directly from you as our relationship and correspondence increases.  In addition, data about you may be obtained from other sources including from your colleagues as the person to speak to regarding a business opportunity or need, from publicly available sources or third parties such as LinkedIn and Zoominfo. Where this is the case, data that we hold will be limited in nature.  WHY WE PROCESS YOUR DATA We need to collect your data so that we can perform and meet our obligations under the contracts we are part for delivering agreed services.  We also collect data so that we can carry out activities which are in the legitimate interests of the Company. We have set these out below:  discuss and secure future business opportunities  business pipelining  making decisions regarding marketing activities  analyze the effectiveness of marketing activities  market intelligence, including analyzing the needs and potential need within the life science industry  maintaining effective correspondence and relationships  ensuring effective business administration  business forecasting including business planning and growth & restructuring exercises  achieving legal compliance and dealing with legal claims made against us  preventing fraud  ensuring our administrative and IT systems are secure and robust against unauthorized access.  With your consent, we collect your personal data to be able to include you on regular company e-mails and marketing correspondence.  SHARING YOUR DATA We may share personal data with:  Employees – where it is necessary for them to undertake their duties.  Service Providers: Third-party vendors who provide services on our behalf (e.g., IT services, marketing, payment processing). These providers are bound by contractual obligations to protect personal data.  Business Partners: In the context of joint offerings, co-branded services, or events.  Legal or Regulatory Authorities: Where required by law, regulation, or court order.  Corporate Transactions: In the event of a merger, acquisition, sale of assets, or bankruptcy.  RQM+ does not and will not sell your data or any personal data to any third party for any reason.  INTERNATIONAL DATA TRANSFERS As a globally operating organization RQM+ may be required to transfer personal data to countries between the USA, EEA, UK and also outside of those countries/jurisdictions.  RQM+ follows the EU-U.S. Data Privacy Framework (with the UK extension) and the Swiss-U.S. Data Privacy Framework, which are established by the U.S. Department of Commerce to regulate the collection, use, and storage of personal information that is transferred from the European Union (EU), United Kingdom (UK), and Switzerland to the United States, respectively.  RQM+ complies with the EU-U.S. Data Privacy Framework (EU-U.S. DPF) and the UK Extension to the EU-U.S. DPF, and the Swiss-U.S. Data Privacy Framework (Swiss-U.S. DPF) as set forth by the U.S. Department of Commerce. RQM+ has certified to the U.S. Department of Commerce that it adheres to the EU-U.S. Data Privacy Framework Principles (EU-U.S. DPF Principles) with regard to the processing of personal data received from the European Union and the United Kingdom in reliance on the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF. RQM+ has certified to the U.S. Department of Commerce that it adheres to the Swiss-U.S. Data Privacy Framework Principles (Swiss-U.S. DPF Principles) with regard to the processing of personal data received from Switzerland in reliance on the Swiss-U.S. DPF. If there is any conflict between the terms in this Privacy Notice and the EU-U.S. DPF Principles and/or the Swiss-U.S. DPF Principles, the Principles shall govern. To learn more about the Data Privacy Framework (DPF) Program, and to view our certification, please visit  https://www.dataprivacyframework.gov/ and https://www.dataprivacyframework.gov/s/participant-search, respectively.  RQM+ shall transfer personal data to a third country or an international organization only if the Controller or Processor has provided appropriate safeguards, and on the condition that enforceable data subject rights and effective legal remedies for data subjects are available.  RQM+ will provide the appropriate safeguards by one or more of the following:  EU-U.S. Data Privacy Framework  A legally binding and enforceable instrument between public authorities or bodies;  Binding corporate rules;  An approved code of conduct together with binding and enforceable commitments of the Controller or Processor in the third country to apply the appropriate safeguards, including data subjects’ rights; or  An approved certification mechanism together with binding and enforceable commitments of the Controller or Processor in the third country to apply the appropriate safeguards, including data subjects’ rights.  RQM+ acknowledges that it is subject to the jurisdiction of the U.S. Federal Trade Commission for compliance and enforcement of the Data Privacy Framework applicable to the EEA, UK, and Switzerland.  Subject to authorization from the competent Supervisory Authority, RQM+ may also provide appropriate safeguards by:  Contractual clauses between RQM+ and the Controller, Processor, or recipient of the personal data in the third country or international organization; or  Provisions inserted into administrative arrangements between public authorities or bodies which include enforceable and effective data subject rights.  RQM+ subsidiaries follow the Data Privacy Framework Principles: Regulatory and Quality Solutions LLC, Maetrics LLC, Regulatory and Quality West LLC, Jordi Labs LLC.  Onward Transfers to Third Parties  We may transfer personal data to third-party service providers who perform functions on our behalf. In such cases, we ensure that these third parties provide at least the same level of protection for personal data as required under the U.S.-EU Data Privacy Framework Principles. We remain liable for the processing of personal data by these third parties unless we can prove we are not responsible for the event giving rise to the damage.  PROTECTING YOUR DATA We prioritize the confidentiality, integrity, and availability of your personal data. Our security measures are designed according to the NIST Cybersecurity Framework and include:  Identify: Regular assessments of systems and assets to manage cybersecurity risks.  Protect: Deployment of encryption, firewalls, and access controls to safeguard data.  Detect: Continuous monitoring and anomaly detection tools to identify threats.  Respond: Established incident response plans for data breaches.  Recover: Comprehensive disaster recovery and business continuity plans to ensure resilience.  These measures are regularly reviewed to meet evolving threats and comply with GDPR Article 32.  HOW LONG WE KEEP YOUR DATA FOR We retain personal data only as long as necessary to fulfill the purposes outlined in this policy or to comply with legal obligations. Retention periods are defined based on:  Legal requirements.  Business needs.  Risk assessments guided by the NIST Cybersecurity Framework.  AUTOMATED DECISION MAKING No decision will be made about you solely on the basis of automated decision making (where a decision is taken about you using an electronic system without human involvement) which has a significant impact on you.  DATA SUBJECT RIGHTS Data Protection Legislation gives citizens and residents in certain jurisdictions rights in relation to the data we hold. Although these rights may not be rights to citizens and residents in other countries and jurisdictions where Data Protection Legislation is limited, RQM+ extends these privileges to all. These are:  Right of Access: Obtain confirmation as to whether personal data concerning you is being processed and receive a copy of your personal data.  Right to Rectification: Request correction of inaccurate or incomplete personal data.  Right to Erasure (“Right to be Forgotten”): Request deletion of your personal data in certain circumstances.  Right to Restrict Processing: Request restriction of processing where certain conditions apply.  Right to Data Portability: Receive the personal data you provided to us in a structured, commonly used, and machine-readable format, and have it transferred to another controller where technically feasible.  Right to Object: Object to processing based on legitimate interests or for direct marketing purposes.  Right to Withdraw Consent: Where processing is based on your consent, you can withdraw consent at any time.  To exercise any of these rights, contact us at dpo@rqmplus.com. We will respond within the timeframe required by applicable law and will honor your request unless an exception applies. Such exceptions may include where fulfillment is necessary to comply with a legal obligation, complete a transaction, detect or prevent fraud or security incidents, support legitimate research or public interest activities, establish or defend legal claims, or where the request cannot be verified or is manifestly unfounded or excessive.  Verification of Your Identity   In order to correctly respond to your privacy rights requests, we need to confirm that YOU made the request. Consequently, we may require additional information to confirm that you are who you say you are.  ​​​For requests submitted via password-protected accounts, your identity is already verified. For requests sent by other means, we will verify your identity via reasonable and proportionate measures, including email or phone call.  We will only use the Personal Data you provide us in a request to verify your identity or authority to make the request.  Verification of Authority  If you submit a request on behalf of somebody else, we will need to verify your authority to act on behalf of that individual. When contacting us, please provide us with proof that the individual gave you signed permission to submit this request, a valid power of attorney on behalf of the individual, or proof of parental responsibility or legal guardianship. Alternatively, you may ask the individual to directly contact us by using the contact details above to verify their identity with RQM+ and confirm with us that they gave you permission to submit this request.  RECOURSE, ENFORCEMENT, AND LIABILITY If you have a privacy or data use concern, we ask that you contact us first at dpo@rqmplus.com. However, if you have an unresolved privacy or data use concern that we have not addressed satisfactorily, then you have the right to use your country’s data protection authority for dispute resolutions (free of charge). To find your country's data protection authority, visit https://edpb.europa.eu/about-edpb/about-edpb/members_en if you are located in the EEA,  https://www.edoeb.admin.ch/edoeb/en/home/deredoeb/kontakt.html if you are located in Switzerland, or  https://ico.org.uk/  if you are located in the UK.   This independent dispute resolution process is provided at no cost to the individual.   Under certain conditions an individual may choose to invoke binding arbitration to resolve any unresolved complaints not resolved by RQM+, but prior to initiating such arbitration, a resident of an EEA country, UK or Switzerland must first (1) contact RQM+ and afford us the opportunity to resolve the issue; (2) seek assistance from the US Department of Commerce directly or through their local data protection authority, and provide the Department time to attempt to resolve the issue.  If an EU or Swiss resident invokes binding arbitration, each party shall be responsible for its own attorneys’ fees. Please be aware that the arbitrator(s) may only impose individual-specific, non-monetary, equitable relief as necessary to remedy any violation of the Privacy Notice with respect to the resident. If an individual formally invokes binding arbitration, RQM+ will follow the terms set forth in Annex 1 of the Data Privacy Framework.   In compliance with the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF and the Swiss-U.S. DPF, RQM+ commits to cooperate and comply respectively with the advice of the panel established by the EU data protection authorities (DPAs) and the UK Information Commissioner’s Office (ICO) and the Swiss Federal Data Protection and Information Commissioner (FDPIC) with regard to unresolved complaints concerning our handling of personal data received in reliance on the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF and the Swiss-U.S. DPF.  For more information on binding arbitration visit: https://www.dataprivacyframework.gov/s/.  Questions or Complaints  If you have any questions about how we protect your personal data or comply with data protection laws of your country or state of residence, you can contact us at dpo@rqmplus.com or at our mailing address:  RQM+ Contact Information:   RQM+ Corporation 5000 Centregreen Way, Suite 100Cary, NC 27513 United States  Data Privacy Officer:  VeraSafe, LLC  100 M Street S.E., Suite 600 Washington, D.C. 20003 United States of America Tel: +1 (617) 398-7067 Email: experts@verasafe.com Web: https://www.verasafe.com/about-verasafe/contact-us/  EU Representative:  RQM+ Eschersheimer Landstraße 14, 60322 Frankfurt am Main  UK Representative:  RQM+ 3rd Floor 1 Ashley Road, Altrincham, Cheshire, WA14 2DT  We will work with you to resolve your issue.  Requirement to Disclose  We may disclose personal data when we have a good faith belief that such action is necessary to: conform to legal requirements or to respond to lawful requests by public authorities, including to meet national security or law enforcement requirements; or to enforce our contractual obligations.  Regulatory Oversight  RQM+ is subject to the investigatory and enforcement powers of the United States Federal Trade Commission (FTC).  Changes to this Privacy Notice  RQM+ reserves the right to change this Privacy Notice from time to time. RQM+ will maintain its current policy on this website so please check here to see the latest updates, which will be noted by the Effective Date. Your continued use of the RQM+ website, RQM+, and any other services offered by RQM+ after such modifications will constitute your: (a) acknowledgment of the modified Privacy Notice; and (b) agreement to abide and be bound by that Notice.  Updated May 2026  #### Regulatory & Quality Backed by 50+ years of direct FDA experience, we offer MedTech regulatory affairs and quality assurance solutions that help innovators achieve and maintain global compliance. From product development to post-market support, our integrated approach equips you to stay ahead of evolving standards while keeping your product pipeline on track.  Whether you’re launching, scaling, remediating, or acquiring, we deliver the insights and execution needed for long-term regulatory success.  Ready to stay ahead of the curve? Let’s move your product forward—faster, safer, and with confidence. Get Regulatory & Quality Support The MedTech Regulatory Risk Map: A Global Life Cycle Navigation Guide In the global MedTech market, regulatory risk is cumulative and asymmetric: it’s a Risk Amplification Engine. What clears the path for the FDA might create a dead end for CMS or an “Evidence Trap” under EU MDR. Use this interactive map to diagnose regional risk factors across the 7 stages of the product life cycle. The Risk Amplification Engine: 7 Stages of the MedTech Life Cycle Click each stage to see how one decision creates diverging global realities. Explore Our Regulatory & Quality Services Tailored Guidance for Every Stage of Your Product Life Cycle No matter where you are in your MedTech journey, our regulatory & quality services are designed to meet your unique challenges. Explore our customized solutions below.  Design Quality Engineering & Manufacturing QA  RQM+ integrates regulatory insight with design and manufacturing quality assurance to ensure your product meets global standards from the ground up. Our experts support design history file (DHF) development, design control optimization, and integration of quality processes into manufacturing environments to minimize risk and ensure compliance. Post-Market Clinical Follow-Up (PMCF) We provide expert strategy and execution for PMCF to meet evolving EU MDR requirements. Our team develops actionable PMCF plans and reports that satisfy notified body expectations, reduce regulatory delays, and help you continuously monitor product performance and safety in the field. Combination Products Regulatory Support Our team understands the nuanced requirements for drug-device and biologic-device combinations. We develop regulatory strategies aligned with U.S. FDA and EU expectations, providing expert support across development, submissions, and post-market compliance for combination products. CAPA & Complaints RQM+ streamlines your CAPA and complaints processes, quickly identifying root causes and implementing sustainable resolutions, reducing compliance risks and enhancing patient safety. Quality Management Systems We build and enhance QMS programs that are scalable, inspection-ready, and aligned with ISO 13485, FDA QSR, EU MDR and IVDR, MDSAP, and more. Whether you need support for initial implementation, optimization, or full remediation, we deliver right-sized systems tailored to your operations. Acquisition Integration & Quality System Harmonization Mergers and acquisitions (M&A) require seamless quality system integration. RQM+ offers proven strategies to consolidate and harmonize QMSs across legacy organizations, minimizing disruption and accelerating compliance across multisite operations.  Proven Global Regulatory Success Whether you're navigating regional regulatory challenges or managing global compliance, RQM+ delivers the strategic insights and execution that drive results. Our team of seasoned professionals — including former regulators and industry specialists — brings unmatched experience across therapeutic areas and device types. Supplier & Purchasing Controls We help you establish robust supplier and purchasing controls, ensuring quality throughout your supply chain to consistently meet regulatory expectations and maintain operational excellence. RQM+ RA/QA consulting encompasses a wide spectrum of specialties with hundreds of industry-leading consultants across the globe. Our strategic acumen and first-hand experience spans medical devices, IVDs, software-enabled products, combination products, and companion diagnostics. RQM+ understands the nuances and decisions our clients confront across device types. While MedTech regulations continue to evolve, our team remains at the forefront and primed to help our clients navigate RA/QA challenges with business-balanced solutions.  Why Choose RQM+ for RA/QA Services? We apply our comprehensive expertise and innovative tools to accelerate your success: Proven Success Across MedTech Join other innovators who trust RQM+ to deliver exceptional results.  “I wanted to extend my thanks and appreciation for all of the RQM+ team and especially our project lead. I've been doing this for almost 20 years with multiple FDA clearances, so I know how nontrivial it is to be a professional in our field. Our project lead is a true expert with significant knowledge, experience and a very balanced common sense. Moreover, they have a rare talent to differentiate between major and minor, and by this to allow the leading team to focus on the more critical aspects of the submission. At the beginning of the project, I've evaluated several groups and decided to move forward with RQM+, especially due to the impression I got from our project lead and it proved itself. Again, many thanks and for many more successful projects. Cheers!” CEO, Innovative MedTech Company “RQM+ provides unrivaled support and has been instrumental in helping our company achieve its regulatory goals. RQM+ is easy to work with, communicates often, and provides high quality deliverables that exceed expectations. I cannot recommend their services enough!” Regulatory Compliance Manager, Innovative MedTech Company “Our quality and regulatory expert is a reliable resource always willing to help and consistently providing clear, actionable responses.” Senior Regulatory Affairs Specialist, Innovative MedTech Company “If our regulatory consultant were my only experience with RQM+, I'd be rating her an 11 instead of a 10! Truly excellent.” Senior Regulatory Affairs Specialist, Innovative MedTech Company “You have rockstars on your team who are true experts in all things med device regulatory! I have had positive experiences with all RQM+ colleagues and it was reassuring to know the team and their expertise was there for guidance.” Principal Regulatory Specialist, Innovative MedTech Company “I was very pleased with the service provided by the 2 regulatory resources that were part of my project. Their level of expertise on the FDA registrations and understanding of the requirements drive us to a successful clearance of 4 different family of products, in addition both of them were always available for consultation within reasonable amount of time.” Project Engineer, Innovative MedTech Company Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Reimbursement​ The path to reimbursement can be as complex as the product development process itself, but it’s a critical step in bringing innovative medical technologies to market. Our team of seasoned experts combines deep industry knowledge with proven methodologies to deliver reimbursement strategies and services that help you secure coverage, overcome market access challenges, and ensure your product reaches patients fast.   We use decades of regulatory and clinical experience and insights to drive market access and increase revenue, supporting your product’s success.  Start Now  Explore Our Reimbursement Services Our suite of reimbursement services includes: Reimbursement Strategy Development Lay the groundwork for reimbursement success with customized strategies that are designed for your product’s unique needs.  Reimbursement Strategy Development Payer Research & Gap Analysis Gain critical insights into payer expectations and identify gaps in evidence to optimize your reimbursement pathway.  Payer Research & Gap Analysis Health Economics Demonstrate the value of your product through robust health economics and outcomes research.  Health Economics Market Access Road Map Lay the groundwork for market access with a detailed, step-by-step plan that positions your product for success. Market Access Road Map Coding & Billing Ensure accurate coding and streamlined billing processes to maximize your reimbursement potential.  Coding & Billing Why Choose RQM+ for Reimbursement? Because we bring leading expertise to every stage of the reimbursement life cycle: Proven Success in Reimbursement  Join innovators who trust RQM+ to streamline their path to market.  "RQM+ turned our reimbursement challenges into a clear, actionable strategy. Their expertise is unmatched. The RQM+ employees I worked with were outstanding in their levels of professionality, experience, friendly personalities, work ethic (very hard workers) and output." Senior Regulatory Manager, Innovative MedTech Company "RQM+ has been very helpful and great to work with, very thorough, organized, accommodating and knowledgeable." Senior Manager, Clinical Affairs Operations, Innovative MedTech Company Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Remediation When a compliance issue threatens your progress, regulatory findings from agencies like the FDA, notified bodies, and other global authorities can disrupt operations and delay your product’s success. Additionally, significant regulatory changes like the EU MDR and IVDR, can require extensive updates to technical documentation and quality systems. Mergers and acquisitions (M&A) can also require remediation support integrating quality systems, aligning regulatory documentation, or addressing compliance gaps that are exposed during due diligence.  What’s your best move at this critical time? Partnering with a team filled with former regulators and industry insiders.  At RQM+, we specialize in creating a culture of quality to accelerate your compliance and speed market success, all while minimizing risks. With decades of medical device regulatory support experience, we guide you through every step of the remediation process. When quality matters most, RQM+ has your back.  Start Now  Your Medical Device Remediation Services Benefits Partnering with RQM+ for remediation ensures: Core Remediation Services Global Regulatory Engagement Strategic responses to findings from the FDA, notified bodies, and other authorities  Consent decree resolution and management  Support for international regulatory audits and reviews  Quality System Remediation Gap analysis and corrective action plans  Full quality system redesign and implementation for ISO 13485, QMSR, MDR, and other global standards  Technical Documentation Updates Addressing deficiencies in Design History Files (DHF) and technical documentation  Remediation of Clinical Evaluation Reports (CER) and Performance Evaluation Reports (PER)  Audit and Inspection Readiness Mock audits and inspection preparation for the FDA, notified bodies, and other agencies  Proactive risk assessments and mitigation strategies  Regulatory Compliance Oversight Realignment of labeling, standards, and risk management practices  Ongoing monitoring to ensure sustained compliance  Helping Our Partners Put Remediation in the Rear View Partnered with leading medical device manufacturers to address FDA warning letters and global audit findings  Supported clients in achieving successful remediation outcomes through comprehensive quality system redesigns and strategic regulatory engagement  Helped clients navigate consent decrees with tailored compliance strategies and ongoing oversight  Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages for:  Comprehensive IVD, Combination, and Medical Device Regulatory Support for Remediation Needs Regulatory challenges don’t have to derail your success. With RQM+ by your side, you can address compliance issues confidently. Let’s tackle your compliance obstacles together and safeguard your MedTech product’s long-term impact.  #### Remediation Studies When compliance issues threaten your clinical trials, swift action is a must. We specialize in IVD, combination product, and medical device remediation studies that address regulatory findings, resolve compliance issues, and support your product’s journey to market.   With decades of experience and a team of former regulators, we provide the strategic guidance to turn challenges into opportunities and ensure your program’s long-term success.  Start Now  Why Choose RQM+ for IVD, Combination, and Medical Device Remediation Studies? Partnering with RQM+ for remediation studies delivers robust benefits, including:  Core Services for Remediation Our remediation study expertise addresses trial-specific challenges, including:  Regulatory Engagement for Clinical Trials Strategic responses to clinical trial deficiencies identified by regulatory bodies  Resolving trial-specific FDA warning letters, notified body audit findings, and other compliance issues Data Integrity and Documentation Updates Validating clinical trial data to meet regulatory expectations  Addressing deficiencies in trial protocols, safety data, and evaluation reports Protocol Redesign and Risk Mitigation Correcting flawed trial protocols to ensure regulatory compliance  Proactive risk management to avoid future compliance setbacks Inspection Readiness for Trials Preparing clinical trial sites for inspections and audits  Conducting mock audits and offering strategic guidance to address potential findings Expertise in FDA Warning Letters  How do you decide what is “good enough,” and how do you align with the regulators on this decision? What are some best practices for DHF remediation efforts? Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages:  Medical Device Remediation Experts Regulatory challenges don’t have to derail your program. With RQM+ as your trusted remediation partner, you can confidently address compliance issues: Achieve regulatory clearance for products under consent decree Reduce your response timelines to regulatory findings Prevent repeat FDA observations #### Resource Library Access our collection of MedTech resources, including white papers, case studies, webinars, and more. Use the filters to find exactly what you need.  Back to Top Making MedTech Happen with RQM+ Tune in to hear RQM+ experts and special guests discuss industry updates, best practices, and challenges relevant to MedTech professionals. Subscribe on Spotify, Apple Podcasts, and other platforms. Listen to the Podcast #### RQM+ Acting as a Data Processor (Privacy Notice Addendum) INTRODUCTION RQM+ and its subsidiaries (“We,” “Us”) is committed to protecting the privacy and security of personal data that we process on behalf of other organizations (the “Controller”). This Privacy Notice Addendum (“Addendum”) explains how we, as a Data Processor under the EU-UK-GDPR and Swiss General Data Protection Regulation, process personal data strictly in accordance with our contractual obligations and the Controller’s instructions. ROLE AS DATA PROCESSOR We act as a Data Processor (“Processor”) for our clients, who are the Data Controllers (“Controller”) responsible for determining the purposes and means of the personal data processing. Our processing activities are governed by a Data Processing Agreement (DPA) or other contractual arrangements between RQM+ and the Controller. We do not control or own the personal data that we process on behalf of our clients ENGAGING ANOTHER PROCESSOR RQM+ shall not engage another Processor without prior written authorization of the Controller. RQM+ shall inform the Controller of any intended additions/replacements of other Processors, so the Controller has the opportunity to object to such changes. If another Processor is engaged, the same contractual obligations between the Controller and RQM+ are required of other Processors as specified in a binding contract or other legal act, and the initial Processor remains fully liable for any failure to meet obligations under that contract. TYPES OF PERSONAL DATA PROCESSED As a Processor, our clients will be providing RQM+ pseudonymized data produced from certified Clinical Trials platforms used to collect Personal data and utilizing technology designed to create Pseudonymized data.  What is Pseudonymized Data? Pseudonymized data refers to personal data that has been processed in such a way that it can no longer be attributed to a specific individual without the use of additional information. This additional information is kept separately and is subject to strict technical and organizational controls to ensure the data cannot be re-identified.  Examples of pseudonymized data include:  Unique identifiers (e.g., pseudonyms or codes) that replace identifiable information. Data processed for research, statistical, or analytical purposes with direct identifiers removed. Purposes of Processing Pseudonymized Data We process pseudonymized data for the following purposes:  Research and analytics to improve our services.  Compliance with legal or regulatory requirements.  Enhancing security and preventing unauthorized access to sensitive data.  Supporting anonymized reporting for business insights.  We ensure that pseudonymized data is used only for legitimate and clearly defined purposes.  Lawful Basis for Processing  RQM+ shall process personal data in accordance with all applicable laws and contractual obligations, and will not process personal data unless at least one (1) of the following six (6) requirements are met:  Consent: The data subject has given consent to the processing of their personal data for one or more specific purposes;  Contract: The processing is necessary for the performance of a contract the data subject is party to, or to take steps requested by the data subject prior to entering into a contract;  Legal obligation: The processing is necessary for compliance with a legal obligation;  Vital interest: The processing is necessary to protect the vital interests of the data subject or of another natural person;  Public task: The processing is necessary for the performance of a task carried out in the public interest or in exercising official authority vested in RQM+ ;  Legitimate interest: Processing is necessary for the legitimate interests of RQM+ or a third party unless those interests are overridden by the interests or fundamental rights and freedoms of the data subject.  Some circumstances allow personal data to be further processed for purposes beyond the original purpose for which the data was collected. When determining the compatibility of a new processing purpose, guidance and approval shall be obtained from the DPO before any such processing occurs. RQM+ shall consider the following to determine if further processing is for a purpose that is compatible with the original purpose:  Any link between the purpose for which the personal data was collected and the reasons for intended further processing;  The context in which the personal data has been collected, particularly the relationship between data subjects and the Controller;  The nature of the personal data, particularly whether special categories of data, or personal data related to criminal convictions and offenses are being processed;  The possible consequences of the intended further processing for the data subject; and  The existence of appropriate safeguards for further processing, which may include encryption, anonymization, or pseudonymization.  SPECIAL CATEGORIES OF DATA  RQM+ will only process special categories of data where the data subject explicitly consents to such processing or where one of the following conditions apply:  The processing is necessary to protect the vital interests of the data subject or another natural person where the data subject is incapable of giving consent;  The processing involves data that has already been made public by the data subject;  The processing is necessary for the establishment, exercise, or defense of legal claims  The processing is specifically authorized or required by law or for a judicial process; and  Personal data is processed under the obligation of professional secrecy under law or rules established by national competent bodies (e.g., HIPAA).     In any case where special categories of data are to be processed, prior approval shall be obtained from the DPO and the purpose for processing is clearly recorded with the related personal data. When processing such data, RQM+ shall also adopt additional technical and organizational data protection measures.  Processing of personal data relating to criminal convictions and offenses shall be performed only under the control of official authority or when the processing is authorized by law and additional data protection measures are adopted to protect the rights and freedoms of data subjects.  How We Ensure the Security of Pseudonymized Data We implement robust technical and organizational measures to safeguard pseudonymized data, including:  Data encryption and secure storage of pseudonymization keys separately from the pseudonymized dataset.  Access controls to limit access to authorized personnel only.  Regular security audits and testing to identify and address vulnerabilities.  Policies and procedures for securely managing and deleting pseudonymized data when no longer needed.  Retention Period Pseudonymized data will be retained for as long as necessary to fulfill the purposes outlined in our contracts with the Data Controller, or as required by law. After the retention period, pseudonymized data will be securely deleted or further anonymized.  Sharing and Disclosure of Pseudonymized Data  We do not share pseudonymized data with third parties unless:  You have provided explicit consent.  It is necessary for fulfilling a contractual obligation.  We are legally required to disclose data.  We engage trusted service providers to process data on our behalf, subject to strict contractual safeguards.  We will only disclose personal data to:  Authorized Sub-processors: Third parties engaged by us to assist in providing services to the Controller, such as platforms used in clinical trials.All sub-processors are subject to written agreements that bind them to data protection obligations comparable to those in our agreement with the Controller. We ensure that third parties adhere to GDPR standards when handling pseudonymized data.  Legal or Regulatory Authorities: Only as required by law or a valid court order, and where feasible, we will promptly inform the Controller before disclosing data. DATA SECURITY We prioritize the confidentiality, integrity, and availability of your personal data. Our security measures are designed according to the NIST Cybersecurity Framework and include:  Identify: Regular assessments of systems and assets to manage cybersecurity risks.  Protect: Deployment of encryption, firewalls, and access controls to safeguard data.  Detect: Continuous monitoring and anomaly detection tools to identify threats.  Respond: Established incident response plans for data breaches.  Recover: Comprehensive disaster recovery and business continuity plans to ensure resilience.  These measures are regularly reviewed to meet evolving threats and comply with GDPR Article 32.  DATA STORAGE Location of Data Storage – Your personal data is stored on secure servers in the United States and/or the European Union. We ensure that these storage facilities comply with GDPR requirements for data security and protection.  Cloud Storage Providers – If we use cloud storage services, these may involve data processing and storage in different regions. For example, some of our service providers may operate servers in the United States and/or the European Union. We only work with vendors that offer GDPR-compliant terms and ensure data security through encryption and access controls.  BREACH REPORTING Notification of Personal Data Breaches – If RQM+ becomes aware of a personal data breach, it will notify the relevant Controller without undue delay. Most Controllers will expect to be notified immediately, and may contractually require this, as they only have a limited time in which to notify the supervisory authority (such as the ICO). RQM+ will also assist the Controller in complying with its obligations regarding personal data breaches.  Notification of Potential Data Protection Infringements – RQM+ will notify the Controller immediately if any of their instructions would lead to a breach of the GDPR or local data protection laws.  Accountability Obligations – RQM+ will comply with GDPR accountability obligations, such as maintaining records and appointing a Data Protection Officer.  DATA DELETION Best Practices used in our Data Deletion process;  Audit and Inventory Data: Maintain an up-to-date inventory of stored data to ensure complete deletion when required.  Document Deletion Processes: Keep records of data deletion, including methods used and the date of deletion, for accountability.  Certify Deletion: Obtain certification or reports when using third-party services for data erasure.  Periodic Testing: Regularly test deletion processes to ensure compliance and effectiveness.  DATA DELETION METHODS Data that is no longer needed is securely deleted or anonymized. Several methods may be used to delete data depending on the storage technology, these include;  Overwriting – Use certified software tools that comply with standards like NIST SP 800-88 Guidelines for Media Sanitization or ISO/IEC 27040.  Encryption with Key Destruction – Encrypting data and securely deleting or destroying the encryption key, making the data irretrievable.  Data Anonymization – Irreversibly modifying data to remove the ability to link it to individuals.  Cloud Storage Deletion – Instructing cloud providers to delete data in compliance with GDPR, ensuring that data is removed from:  Active servers.  Backups and redundant systems.  DATA SUBJECT RIGHTS As a data processor, we assist the Controller in fulfilling its obligations with respect to data subjects’ rights under the GDPR. If we receive any request from a data subject to exercise rights (such as access, rectification, erasure, etc.), we will promptly forward the request to the Controller. We do not respond directly to data subject requests unless expressly authorized by the Controller.  INTERNATIONAL TRANSFERS As a globally operating organization, RQM+ may be required to transfer personal data to countries between the USA, EEA, UK, Switzerland and also outside of those countries/jurisdictions.  RQM+ follows the EU-U.S. Data Privacy Framework (with the UK extension) and the Swiss-U.S. Data Privacy Framework (https://www.dataprivacyframework.gov/), which are established by the U.S. Department of Commerce to regulate the collection, use, and storage of personal information that is transferred from the European Union (EU), United Kingdom (UK), and Switzerland to the United States, respectively.  RQM+ complies with the EU-U.S. Data Privacy Framework (EU-U.S. DPF) and the UK Extension to the EU-U.S. DPF, and the Swiss-U.S. Data Privacy Framework (Swiss-U.S. DPF) as set forth by the U.S. Department of Commerce. RQM+ has certified to the U.S. Department of Commerce that it adheres to the EU-U.S. Data Privacy Framework Principles (EU-U.S. DPF Principles) with regard to the processing of personal data received from the European Union and the United Kingdom in reliance on the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF. RQM+ has certified to the U.S. Department of Commerce that it adheres to the Swiss-U.S. Data Privacy Framework Principles (Swiss-U.S. DPF Principles) with regard to the processing of personal data received from Switzerland in reliance on the Swiss-U.S. DPF. If there is any conflict between the terms in this privacy notice and the EU-U.S. DPF Principles and/or the Swiss-U.S. DPF Principles, the Principles shall govern. To learn more about the Data Privacy Framework (DPF) Program, and to view our certification, please visit https://www.dataprivacyframework.gov/ and https://www.dataprivacyframework.gov/s/participant-search, respectively. RQM+ shall transfer personal data to a third country or an international organization only if the Controller or Processor has provided appropriate safeguards, and on the condition that enforceable data subject rights and effective legal remedies for data subjects are available.  RQM+ will provide the appropriate safeguards by one or more of the following:  EU-U.S. Data Privacy Framework  A legally binding and enforceable instrument between public authorities or bodies;  Binding corporate rules;  An approved code of conduct together with binding and enforceable commitments of the Controller or Processor in the third country to apply the appropriate safeguards, including data subjects’ rights; or  An approved certification mechanism together with binding and enforceable commitments of the Controller or Processor in the third country to apply the appropriate safeguards, including data subjects’ rights.  RQM+ acknowledges that it is subject to the jurisdiction of the U.S. Federal Trade Commission for compliance and enforcement of the Data Privacy Framework applicable to the EEA, UK, and Switzerland.  Subject to authorization from the competent Supervisory Authority, RQM+ may also provide appropriate safeguards by:  Standard Contractual Clauses (“SCCs”) between RQM+ and the Controller, Processor, or recipient of the personal data in the third country or international organization; or  Provisions inserted into administrative arrangements between public authorities or bodies which include enforceable and effective data subject rights.  RQM+ subsidiaries follow the Data Privacy Framework Principles: Regulatory and Quality Solutions LLC, Maetrics LLC, Regulatory and Quality West LLC, Jordi Labs LLC.  Onward Transfers to Third Parties  We may transfer personal data to third-party service providers who perform functions on our behalf. In such cases, we ensure that these third parties provide at least the same level of protection for personal data as required under the U.S.-EU Data Privacy Framework Principles. We remain liable for the processing of personal data by these third parties unless we can prove we are not responsible for the event giving rise to the damage.  COOPERATION WITH SUPERVISORY AUTHORITIES RQM+ will cooperate with supervisory authorities to help them perform their duties.  RECOURSE, ENFORCEMENT, AND LIABILITY If you have a privacy or data use concern, we ask that you contact us first at dpo@rqmplus.com. However, if you have an unresolved privacy or data use concern that we have not addressed satisfactorily, then you have the right to use your country’s data protection authority for dispute resolutions (free of charge). To find your country’s data protection authority, visit https://edpb.europa.eu/about-edpb/about-edpb/members_en if you are located in the EEA,  https://www.edoeb.admin.ch/edoeb/en/home/deredoeb/kontakt.html if you are located in Switzerland, or https://ico.org.uk/  if you are located in the UK.   This independent dispute resolution process is provided at no cost to the individual.   Under certain conditions an individual may choose to invoke binding arbitration to resolve any unresolved complaints not resolved by RQM+, but prior to initiating such arbitration, a resident of an EEA country, UK or Switzerland must first (1) contact RQM+ and afford us the opportunity to resolve the issue; (2) seek assistance from the US Department of Commerce directly or through their local data protection authority, and provide the Department time to attempt to resolve the issue.  If an EU or Swiss resident invokes binding arbitration, each party shall be responsible for its own attorneys’ fees. Please be aware that the arbitrator(s) may only impose individual-specific, non-monetary, equitable relief as necessary to remedy any violation of the privacy notice with respect to the resident. If an individual formally invokes binding arbitration, RQM+ will follow the terms set forth in Annex 1 of the Data Privacy Framework.   In compliance with the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF and the Swiss-U.S. DPF, RQM+ commits to cooperate and comply respectively with the advice of the panel established by the EU data protection authorities (DPAs) and the UK Information Commissioner’s Office (ICO) and the Swiss Federal Data Protection and Information Commissioner (FDPIC) with regard to unresolved complaints concerning our handling of personal data received in reliance on the EU-U.S. DPF and the UK Extension to the EU-U.S. DPF and the Swiss-U.S. DPF.  For more information on binding arbitration visit:  https://www.dataprivacyframework.gov/s/)  Questions or Complaints  If you have any questions about how we protect your personal data or comply with data protection laws of your country or state of residence, you can contact us at dpo@rqmplus.com or at our mailing address:  RQM+ Contact Information:   RQM+ Corporation 5000 Centregreen Way, Suite 100 Cary, NC 27513United States  Data Privacy Officer:  VeraSafe, LLC  100 M Street S.E., Suite 600 Washington, D.C. 20003 United States of America Tel: +1 (617) 398-7067 Email: experts@verasafe.com Web: https://www.verasafe.com/about-verasafe/contact-us/  EU Representative:  RQM+ Eschersheimer Landstraße 14, 60322 Frankfurt am Main  UK Representative:  RQM+ 3rd Floor 1 Ashley Road, Altrincham, Cheshire, WA14 2DT  We will work with you to resolve your issue.  Requirement to Disclose  We may disclose personal data when we have a good faith belief that such action is necessary to: conform to legal requirements or to respond to lawful requests by public authorities, including to meet national security or law enforcement requirements; or to enforce our contractual obligations.  Regulatory Oversight  RQM+ is subject to the investigatory and enforcement powers of the United States Federal Trade Commission (FTC).  Changes to this Privacy Notice  RQM+ reserves the right to change this Privacy Notice from time to time. RQM+ will maintain its current policy on this website so please check here to see the latest updates, which will be noted by the Effective Date. Your continued use of the RQM+ website, RQM+, and any other services offered by RQM+ after such modifications will constitute your: (a) acknowledgment of the modified Privacy Notice; and (b) agreement to abide and be bound by that Notice.  Updated May 2026  #### RQM+ Daily URL: https://www.rqmplus.com/rqm-daily/ #### RQM+ is The MedTech CRO RQM+ is The MedTech CRO — a full-service partner supporting everything from groundbreaking innovation to well-established technologies. Our coordinated and comprehensive solutions are customized to each client’s product and life cycle stage. By aligning strategy and execution in one partner, we help reduce cost, accelerate timelines, and drive more successful outcomes. The Integrated Advantage RQM+ unifies four core service areas to streamline your product life cycle: Being "The" MedTech CRO Means... Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demand professionals, functional service support, fast deployment for tight timelines, and contract-to-hire options that integrate seamlessly with your team. Match with a contractor. Access Device-Specific Expertise Whatever your MedTech area of need, we’ve got you covered. Discover our expertise for your product type:   “The professionalism, attentiveness, and unwavering partnership shown by the team truly impressed us. Their dedication in overcoming challenges and delays significantly advanced our project.” Director of R&D, Contract Testing Laboratory “Great team, great knowledge and insights in helping small, young startups navigate gaining clearance from FDA on new devices.” COO, Global Medical Device Manufacturer #### Social Icons URL: https://www.rqmplus.com/social-icons-39/ #### Software-Enabled Products RQM+ provides regulatory, quality, clinical, post-market, and reimbursement support for medical devices and IVDs, including software-enabled products. Our expertise ensures compliance with FDA, EU MDR, and global standards, addressing AI/ML, cybersecurity, interoperability, and software life cycle management. Start Now  Why RQM+ for Software-Enabled Products? Applicable Regulations & Standards United States FDA 21 CFR Part 820 – Quality System Regulation (QSR) FDA 21 CFR Part 11 – Electronic Records and Signatures FDA 510(k), De Novo, PMA – Regulatory pathways for medical devices NIST Cybersecurity Framework – Cybersecurity risk management IMDRF SaMD Guidance – Software as a Medical Device classification and compliance Canada Health Canada Medical Device Regulations (SOR/98-282) – Regulatory requirements for medical devices ISO 13485:2016 – Quality management systems for medical devices CSA Cybersecurity Standards – Security compliance for networked medical devices Europe EU MDR (2017/745) – Medical Device Regulation for compliance and market access EU IVDR (2017/746) – In Vitro Diagnostic Regulation ISO 14971 – Risk management for medical devices IEC 62304 – Software lifecycle processes for medical device software GDPR (General Data Protection Regulation) – Data privacy and security compliance Integrated Solutions for Software-Enabled Devices Expand each to see our key services. 1. Design Concept Regulatory (US & EU)  Product classification (SaMD vs. SiMD vs. software accessory)  Intended use and claims shaping  IMDRF framework and MDR Annex VIII classification  Early regulatory pathway strategy (e.g., 510(k), De Novo, PMA, CE Mark under MDR) Documents: Regulatory strategy, classification rationale, initial claims matrix  Quality  SDLC alignment to IEC 62304, ISO 13485  Cybersecurity planning per AAMI SW96 and ISO/IEC 81001-5-1 Documents: Risk management plan, draft development SOPs  Clinical  Evidence needs assessment for software-specific performance and human factors Documents: Early clinical evidence roadmap  Reimbursement  Initial payer value story exploration  Identification of digital health reimbursement pathways (e.g., NTAP, CPT codes) Documents: Reimbursement landscape summary  Medical Writing  Drafting of intended use, IFU outline, early labeling strategy Documents: Draft IFU, Target Product Profile  Labs (Jordi Labs)  Only applicable for wearable/implantable devices with sensors Documents: N/A unless hardware present  2. Design & Development Regulatory  Pre-submission strategy (FDA Q-Sub, EU NB consultations)  Standard applicability mapping (FDA Guidance, IEC 62304, ISO 14971) Documents: Pre-sub package, regulatory standard applicability matrix  Quality  Software development documentation including version control, requirements traceability  Secure design documentation and cybersecurity control planning Documents: SDLC documentation, configuration management, secure design traceability  Clinical  Protocol planning for usability testing and validation  Simulation or observational design for performance substantiation Documents: Usability test plan, clinical validation framework  Reimbursement  Planning for evidence to support payer discussions Documents: Preliminary value dossier outline  Medical Writing  Support protocol development, IFU drafting, early CER skeleton (EU) Documents: Draft protocol, CER framework, labeling overview  Labs (Jordi Labs) For wearable/implantable: initiation of device-software integration feasibility testing Documents: N/A unless hybrid product 3. Verification & Validation Regulatory  Support for software V&V documentation aligned to claims  Traceability matrix development and Level of Concern justification Documents: V&V summary, traceability matrix, Level of Concern documentation (FDA)  Quality  Ensure all IEC 62304 and ISO 14971 documentation is audit-ready  Cybersecurity verification protocols documented Documents: Software verification plan, risk control documentation  Clinical  Human factors validation completion  Clinical performance summary (if applicable) Documents: Human factors report, validation data summary  Reimbursement  Alignment of V&V outcomes to support cost-effectiveness arguments Documents: RWE synthesis for value message support  Medical Writing  Support compilation of V&V evidence summaries for regulatory filing Documents: V&V narrative, software summary report for FDA/EU  Labs  N/A unless wearable/implantable software is integrated with materials Documents: N/A 4. Clinical Evidence Generation Regulatory  Submission of clinical validation justifications or protocols (when required)  Documentation alignment with MDCG 2020-1 (EU) and FDA guidance on SaMD Documents: Clinical protocol (if applicable), justification memo for literature/bench data  Quality  Ensure traceability of clinical inputs to RMF and SDLC records Documents: Clinical-risk linkage analysis  Clinical  Execution or oversight of human factors testing, performance validation, or literature review Documents: CER (EU), Clinical Evaluation Summary (US), SSCP (EU Class C/D)  Reimbursement  Health economic model refinement  Data generation aligned with payer priorities Documents: HEOR plan, payer evidence gap analysis  Medical Writing  Clinical Study Reports, CER updates, Post-Market Clinical Follow-Up Plans (EU) Documents: CSR, CER, PMCF Plan  Labs (Jordi Labs) N/A unless clinical integration with device performance Documents: N/A  5. Manufacturing Readiness Regulatory  Finalization of submission components (510(k), De Novo, MDR Tech File)  Labeling and UDI content review Documents: Labeling packet, eSTAR checklist, EU GSPR table  Quality  Completion of QMS documentation related to software production  Software release documentation and cybersecurity deployment validation Documents: Finalized DHF, SOPs for release, software change control plan  Clinical  Continued support for integrating usability and clinical performance outcomes into QMS Documents: Clinical evidence integration memo  Reimbursement  Prepare value proposition materials for launch market access planning Documents: Reimbursement dossier, payer slide deck  Medical Writing  IFU finalization, submission narratives, PMCF plan content Documents: Final IFU, PMCF Plan  Labs (Jordi Labs) N/A unless software controls hardware interaction in implantables Documents: Device-software interoperability report (if applicable)  6. Regulatory Submissions Regulatory  Complete 510(k), De Novo, PMA, or MDR Tech Doc preparation and submission  Response to AI/IR, RTA, Notified Body feedback Documents: Entire regulatory submission packet, RTA checklist, NB response memos  Quality  Support linking submission to QMS audit readiness Documents: Quality documentation list, audit support memo  Clinical  Final submission of all clinical reports Documents: Clinical Summary, Clinical Evidence Table  Reimbursement  Initiate payer submission strategy or clinical coding review Documents: Coding memo, payer outreach plan  Medical Writing  Own authorship of submission content (intended use, clinical summary, labeling) Documents: FDA Summary of Safety and Effectiveness, EU Clinical Overview  Labs (Jordi Labs) Not typically involved unless integrated hardware Documents: N/A  7. Market Access & Launch Regulatory  Marketing clearance communication, labeling compliance checks Documents: CE Certificate/510(k) letter, labeling confirmation report  Quality  Software release to production documentation Documents: Final DHF, deployment SOPs  Clinical  Launch evidence support and post-launch surveillance setup Documents: Post-market plan, user feedback protocol  Reimbursement  Initiation of reimbursement submissions or coding applications Documents: Payer communication documents, CMS submission (if US)  Medical Writing  PMCF implementation documents, launch messaging materials Documents: PMCF Report template, value-focused clinical brief  Labs  Only applicable in hybrid wearable/implantable products Documents: N/A unless triggered by combination use 8. Post-Market Activities Regulatory  Support for periodic updates (e.g., PSURs), vigilance reporting Documents: PSUR (EU), MDR vigilance reporting support  Quality  Software change control documentation support Documents: Change justification memos, cybersecurity update logs  Clinical  PMCF activities and registry/RWD support Documents: PMCF data reports, literature monitoring logs  Reimbursement  Continued evidence generation for value-based care models Documents: Real-world outcomes tracking sheet  Medical Writing  Periodic update support and narrative responses Documents: PSUR summary, client-facing safety narrative  Labs  Not applicable  9. Life Cycle Management and Expansion Regulatory  Label expansions, software feature enhancements, international registrations Documents: Change notification documents, global submission strategies  Quality  Validation support documentation for updates Documents: Validation summary support, QMS update documentation  Clinical  Ongoing studies or new indication assessments Documents: Study protocols, evidence expansion map  Reimbursement  Global payer engagement strategy for new markets Documents: Global reimbursement landscape  Medical Writing  Authoring of regulatory justifications and updated submission components Documents: Clinical Addenda, Summary of Change Justification  Labs  Not applicable  10. Emergency Support Regulatory  Crisis response for recalls, MDR reporting, field corrective action Documents: Field Safety Notice, CAPA support documentation  Quality  CAPA support, DHF remediation Documents: Root cause analysis, correction plan  Clinical  RWE rescue studies or performance complaints Documents: Complaint analysis report  Reimbursement  Evidence rebuttals or coverage challenges Documents: Appeals support packet  Medical Writing  Urgent communications and supporting regulatory narratives Documents: Safety memo, regulator communication template  Labs  Only if linked to physical component issue Documents: N/A unless combination  Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Solutions RQM+ is your MedTech solutions partner, supporting medical devices, IVDs, software-enabled products, and combination products. As The MedTech CRO, we help you navigate every stage of your product life cycle with integrated, end-to-end solutions across all therapeutic areas and device types to bring your product to patients — faster, safer, better. SMART Solutions As a full-service MedTech CRO, our SMART Solutions deliver end-to-end alignment across regulatory, quality, clinical, reimbursement, and labs from concept through post-market, lowering risk, increasing clarity, and maximizing your odds of market success. Designed for the complexity of modern MedTech, from AI/ML enabled devices, software enabled products, and combination products to multi-region regulatory strategies, you get the clarity, control, and execution you need. SMART Solution Models SMART Solutions operates in two intentional models to fit your organization’s needs: Integrated SMART Solutions We bring your full life cycle orchestration across all functions — from regulatory, quality, and clinical to reimbursement and labs — under a single governance structure to simplify your efforts and streamline your journey from early development through post-market. Functional SMART Solutions We provide deep, structured support within a specific discipline — like quality, clinical, or labs — to mirror how you already operate while ensuring strategy-led, KPI-driven execution. The RQM+ SMART Advantage By embedding our experts directly within your teams and integrating a single operating system and strategy‑led decision‑making, SMART Solutions delivers: Differentiated labs capability Using our differentiated lab capabilities, which include AI‑enabled Lumo™ and Jordi Labs’ proprietary data, we clarify E&L and biocompatibility risks earlier before they become surprises, recalls, or rework. Structured execution We engineer a single operating system for your entire MedTech life cycle to support earlier visibility into regulatory, lab, clinical, and market access risks — so your teams can act before issues become costly delays, rework, or fire drills. Predictable governance SMART Solutions is anchored in KPI‑driven governances with clear roles, decision rights, dashboards, and review cadences to keep programs on track and aligned with your business goals. Increased efficiencies SMART Solutions includes embedded expert teams that work within your systems and tools, acting as an extension of internal functions while maintaining RQM+ methodologies and standards. The result? Integrated planning, fewer handoffs, and reusable frameworks that reduce resets and duplicate work while giving you greater predictability and efficiency. Scalable capacity SMART Solutions integrates RQM+’s full capabilities, including regulatory strategy, design controls and QMS, lab and materials science, clinical evidence generation, reimbursement, and market access. Whether you need a full-service integration or functional support, we can start with a focused need and scale horizontally across your life cycle and vertically within your functions, ensuring continuity and measurable outcomes as your program evolves — without adding internal headcount or onboarding new vendors. Life cycle continuity RQM+ has proven strength in high‑pressure areas including MDR/IVDR surge support, post‑market surveillance and remediation, complex safety and materials questions, and high‑urgency “fire drills.” Using that skill, we establish your regulatory pathway, evidence strategy, and governance structure early to reduce downstream risk, rework, and fragmentation and satisfy MDR/IVDR, FDA, and payer expectations from the start. Differentiated labs capability  Using our differentiated lab capabilities, which include AI‑enabled Lumo™ and Jordi Labs’ proprietary data, we clarify E&L and biocompatibility risks earlier before they become surprises, recalls, or rework. Predictable governance SMART Solutions is anchored in KPI‑driven governances with clear roles, decision rights, dashboards, and review cadences to keep programs on track and aligned with your business goals. Scalable capacity SMART Solutions integrates RQM+’s full capabilities, including regulatory strategy, design controls and QMS, lab and materials science, clinical evidence generation, reimbursement, and market access. Whether you need a full-service integration or functional support, we can start with a focused need and scale horizontally across your life cycle and vertically within your functions, ensuring continuity and measurable outcomes as your program evolves — without adding internal headcount or onboarding new vendors. Structured execution We engineer a single operating system for your entire MedTech life cycle to support earlier visibility into regulatory, lab, clinical, and market access risks — so your teams can act before issues become costly delays, rework, or fire drills. Increased efficiencies SMART Solutions includes embedded expert teams that work within your systems and tools, acting as an extension of internal functions while maintaining RQM+ methodologies and standards. The result? Integrated planning, fewer handoffs, and reusable frameworks that reduce resets and duplicate work while giving you greater predictability and efficiency. Life cycle continuity RQM+ has proven strength in high‑pressure areas including MDR/IVDR surge support, post‑market surveillance and remediation, complex safety and materials questions, and high‑urgency “fire drills.” Using that skill, we establish your regulatory pathway, evidence strategy, and governance structure early to reduce downstream risk, rework, and fragmentation and satisfy MDR/IVDR, FDA, and payer expectations from the start. Ready to experience the clarity and control of an end-to-end MedTech partnership? Make Your MedTech Program Happen Access Device-Specific Expertise Whatever your MedTech area of need, we’ve got you covered. Discover our expertise for your product type:   Integrated, End-to-End MedTech Solutions Seamlessly connected solutions powered by specialized expertise across four core service areas to advance your MedTech product from concept to market:  “The professionalism, attentiveness, and unwavering partnership shown by the team truly impressed us. Their dedication in overcoming challenges and delays significantly advanced our project.” Director of R&D, Contract Testing Laboratory “Great team, great knowledge and insights in helping small, young startups navigate gaining clearance from FDA on new devices.” COO, Global Medical Device Manufacturer Flexible Partnering Solutions Outsourcing Customizable and scalable outsourcing scoped for entire projects, specific functions, or defined parts of a function. Leverage RQM+ expertise and flexibility while your teams stay focused on core competencies, corporate goals, and innovation. Partner with us. Consulting Targeted, outcome-focused expertise to solve defined MedTech challenges. RQM+consultants step in with practical, actionable guidance and hands-on execution to drive timely resolution. Partner with us. Staff Augmentation Fill skill or capacity gaps with MedTech talent from RQM+. We provide on-demandprofessionals, functional service support, fast deployment for tight timelines, andcontract-to-hire options that integrate seamlessly with your team. Match with a contractor. #### Strategy Development Securing reimbursement for medical devices, diagnostics, and combination products is crucial to market success — but it requires precise planning and deep expertise. At RQM+, we specialize in creating reimbursement strategies for medical devices and related innovations that align with regulatory plans and maximize your market potential.   From understanding payer perspectives to navigating global market access challenges, our seasoned team delivers strategies that work for your program.  Start Now  Benefits of RQM+ Reimbursement Strategy Services Core Reimbursement Strategy Services Our tailored reimbursement strategies for medical devices, diagnostics, and combination products include: Coverage, Coding, and Payment Pathways Develop strategies to secure payer coverage and appropriate reimbursement levels. Payer Perception Analysis Conduct early research to gauge payer acceptance and address potential barriers. Market and Pricing Analysis Analyze market size, pricing models, and competitive positioning to inform decisions. Global Launch Strategies Develop strategies for successful product introduction across international markets. Legacy of Successful Reimbursement Strategies for MedTech Partners  Supported clients in achieving reimbursement success across diverse product categories in U.S. and international markets  Delivered aligned reimbursement and regulatory strategies for smooth transitions from development to market  Partnered with the leading MedTech companies to resolve reimbursement challenges and enable faster product adoption  Device-Specific Expertise #### Sustaining Compliance doesn’t stop at market launch. Sustaining your product’s success requires IVD, combination product, and medical device regulatory compliance consulting services that add vigilance, adaptability, and expert guidance throughout your product’s entire lifecycle. We work closely with you to ensure ongoing compliance, proactive risk mitigation, and constant adaptability in the face of evolving regulatory demands.   Whether it’s post-market surveillance, quality system improvements, or responding to regulatory updates, we give you the support you need to sustain your MedTech innovation.  Start Now  Your MedTech Sustaining Services Benefits When you choose RQM+ for sustaining services, you gain:  Core Medical Device Regulatory Compliance Services Post-Market Surveillance (PMS) Development and integration of PMS plans and reports  Retrospective post-market clinical follow-up (PMCF) and performance follow-up (PMPF) studies  Periodic safety update reports (PSURs)   Quality System Improvements Enhancements for ISO 13485, QSR, MDR, and MDSAP compliance  Internal audits and supplier quality assessments  Mock audits and FDA inspection readiness  Regulatory Compliance Support Strategic responses to audit findings and warning letters  Updates to technical documentation for regulatory changes  Labeling and standards review  Lifecycle Management Proactive remediation strategies for ongoing compliance  Risk management updates aligned with current global standards  Sustaining support for biological evaluation and material testing Our Track Record of Success Partnered with 19 of the top 20 medical device manufacturers to sustain compliance  Proven success in achieving and maintaining ISO 13485 and QSR certificate Supported clients through complex challenges with a high client return rate Device-Specific Expertise Looking for tailored solutions for your specific product type? Explore our dedicated pages:  End-to-End Sustaining Services Across MedTech Nobody wants to repeat themselves over and over at different stages of their journey. One partner who can safely guide you from concept to commercialization saves you time, money, and frustration.  For post-market success, RQM+ brings the expertise, tools, and dedication to ensure your product remains compliant, safe, and impactful — long after launch. We’re your trusted partner for the long haul.  #### Thank you for opting in! We'll periodically share free and exclusive RQM+ content with you, including blogs, white papers, and invitations to our panel discussions and webinars. View our MedTech resource library right now here. Get MedTech insights straight to your inbox #### Thank you for scanning! Share your email and receive access to two white papers from RQM+. Get our white papers now #### Thank you for scanning! Share your email to receive free and exclusive RQM+ content, including blogs, white papers, and invitations to our panel discussions and webinars. Get MedTech insights straight to your inbox #### Thank you! Here are your white papers. Click the hyperlinks to access the PDFs. Trials That Pay: Designing Clinical Studies to Optimize Reimbursement and Market Access Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation View our MedTech resource library right now here. ### Events #### 14th Annual Outsourcing in Clinical Trials: Medical Devices Europe 2026 URL: https://www.arena-international.com/event/octmedeurope/ #### 2025 Regulatory Intelligence Conference Europe URL: https://web.cvent.com/event/d01c990b-e311-4132-8308-0ae96f185de7/summary?utm_campaign=11124480-partner_events_2025_mtaa&utm_medium=email&_hsmi=2&utm_content=2&utm_source=hs_email #### 2025 UK MDR Regulatory Conference URL: https://web.cvent.com/event/0d338e59-28be-47b0-930b-9dc6d7c0e4eb/summary?utm_campaign=11124480-partner_events_2025_mtaa&utm_medium=email&_hsmi=2&utm_content=2&utm_source=hs_email #### ADLM 2025 ADLM 2025, presented by the Association for Diagnostics & Laboratory Medicine (formerly AACC) in partnership with the Canadian Society for Clinical Chemistry, is the premier global event for laboratory medicine. Attendees will connect with leading experts in clinical chemistry, molecular diagnostics, and translational medicine while exploring the latest advancements at the Clinical Lab Expo, featuring 850+ exhibitors and 200+ new products. With over 250 educational opportunities—including lectures, plenary sessions, and roundtables—ADLM 2025 provides an unparalleled opportunity to stay ahead in this rapidly evolving field. #### American Medical Device Summit 2025 URL: https://amdsummit.com/ #### CSMD-Horizon Special Conference for Medtech AI and Digital Health URL: https://csmd-horizon.com/ #### DeviceTalks Boston 2025 DeviceTalks Boston is a two-day event focused on bringing medical devices to market. Hear from industry leaders on engineering, manufacturing, regulatory challenges, and more. Network with experts from major OEMs and start-ups to advance your life-saving technologies. Join us for a comprehensive conference experience. #### Extractables & Leachables West 2025 URL: https://www.pharmaedresources.com/event/extractables-leachables-summit-2025/ #### Global Regulatory Strategy Conference Mastering global regulatory strategy allows for innovative and efficient product development, greater international market access, and competitive advantages. The RAPS 2025 Global Regulatory Strategy Conference will provide you with the latest insights, practical tools, and networking opportunities that can be used to inspire and enhance your global regulatory strategies. #### LSI Emerging MedTech Summit USA 2025 In 2024, LSI USA convened 1,500 executives from emerging companies, venture capital and private equity firms, family offices, global strategics, professional service providers, and more. LSI USA will never be held in a chaotic convention center. It is a curated forum where real business gets done, hosted in world-class venues where senior executives want to do business. #### LSI Europe '25 Emerging Medtech Summit URL: https://www.lsieuropesummit.com/ #### LSI USA '26 Emerging MedTech Summit URL: https://www.lsiusasummit.com/ #### MD&M East 2025 URL: https://www.rqmplus.com/about-us/news-events/events/mdm-east-2025/ #### MedTech Summit 2025 Join RQM+ at this year's MedTech Summit 2025 in Berlin, Germany! Our booth will be active from June 17-19. MedTech Summit 2025 features an unparalleled lineup of over 100 global speakers —including Competent Authorities, Notified Bodies, and top executives from companies like Abbott, Medtronic, Philips, Siemens Healthineers and Stryker. #### Outsourcing in Clinical Trials: Medical Devices USA 2025 Join us at our launch event Outsourcing in Clinical Trials: Medical Devices USA 2025 conference! Gather fresh insights into regulatory updates, trial-running techniques for small companies, and the latest innovations. With presentations and panel discussions on industry trends and outsourcing challenges, this 2-day event is a must-attend for the medical device and diagnostics community. Network with industry peers, collaborate with trial sponsors, manufacturers, and vendors, and tackle post-MDR challenges together. #### PharmaEd Combination Products Summit 2025 URL: https://www.rqmplus.com/about-us/news-events/events/pharmaed-combination-products-summit-2025/ #### RAPS Convergence 2025 RAPS Convergence is the largest and most recognized annual gathering of global regulatory affairs professionals. Convergence brings together representatives of industry, regulatory bodies, research, academia, and clinical organizations that are directly involved in managing the regulatory process and aligning science, regulation, and business strategy. #### RAPS Euro Convergence 2025 RAPS Euro Convergence is the most comprehensive regulatory affairs conference in Europe, focusing on the latest topics and developments in healthcare products in Europe and beyond — with sessions in medical devices, IVDs, pharmaceuticals, combination products, regulatory business, AI, software, and cybersecurity. #### RAPS Euro Convergence 2026 URL: https://www.raps.org/europe-2025/home #### RAPS Global Regulatory Strategy Conference URL: https://grs2026.eventscribe.net/ #### RQM+ Webinar – Bridging the Real-World Evidence Gap SpeakersBethany Chung, PhD, RAC, Director of Technical Solutions and Innovation, RQM+Amelia Hufford, PhD, SVP, Clinical and Regulatory Science Operations, 3Aware Discover how to bridge the gap between real-world evidence ideals and realities, with expert insights, case studies, and practical strategies. #### Smithers Extractables & Leachables U.S.A. 2025 URL: https://www.rqmplus.com/about-us/news-events/events/smithers-extractables-leachables-u-s-a-2025/ #### SOT 64th Annual Meeting and ToxExpo The SOT 64th Annual Meeting and ToxExpo will feature five days of Featured and Scientific Sessions, poster presentations, and social events, as well as the popular three-day ToxExpo. #### The MedTech Conference, hosted by AdvaMed URL: https://themedtechconference.com/ #### Webinar – QMSR is Coming: How to Prepare for FDA’s Alignment with ISO 13485 Speakers: Steve Keverline, Principal Advisor at RQM+ and Tom Rish, Senior Product Marketing Manager at Jama Software Prepare for QMSR: Step-by-Step Guidance for FDA’s ISO 13485 Alignment New Guidance: FDA Safer Technologies Program (STeP) for Medical DevicesOne Year Countdown: Preparing for the FDA’s QMSR Implementation #### Webinar: RWE for Orphan Devices Under New EU Guidance & Beyond Speakers: Bethany Chung, PhD, RAC Senior Manager, Technical-Senior Principal Consultant, RQM+ Amelia Hufford, PhD SVP, Clinical & Regulatory Science Operations, 3Aware Learn how Real-World Evidence supports the assessment and management of orphan devices. #### World Health Expo URL: https://www.worldhealthexpo.com/events/healthcare/dubai/en/home.html ### News #### 3Aware and RQM+ Forge Partnership to Enhance MedTech Compliance and Innovation INDIANAPOLIS, IN – October 28, 2024 – 3Aware, a pioneer in real-world evidence (RWE) solutions for the medical device industry, is pleased to announce a strategic partnership with RQM+, a leading global MedTech service provider. This collaboration marks a significant step in enhancing regulatory compliance and fostering innovation within the MedTech sector. The partnership will combine 3Aware's advanced aiSurveillance technology with RQM+'s comprehensive regulatory expertise to offer an integrated approach to post-market surveillance and compliance for medical device and IVD manufacturers. This synergy aims to transform how companies meet rigorous regulatory requirements while accelerating label expansion and time to market for new and innovative medical devices. "Joining forces with RQM+ aligns with our mission to optimize device portfolios and simplify the complexities of MedTech compliance," said Bill Moss, CEO at 3Aware. "This partnership will leverage our aiSurveillance platform to its fullest potential, ensuring that our clients not only meet but exceed business objectives and evolving regulatory standards." RQM+'s extensive experience in global regulatory pathways will enhance 3Aware's offerings, providing clients with a seamless, efficient pathway through clinical evaluation and regulatory submissions. "We are excited to partner with 3Aware to enhance our service offerings. Together, we will provide a strategic advantage to clients, navigating them through regulatory and business challenges with greater efficiency and accuracy," stated John Potthoff, CEO of RQM+. The partnership will focus on several key areas: Regulatory Grade RWE Generation: 3Aware will enable RQM+ to provide clients with full patient EHR records related to a device or group of devices. This approach accelerates study timelines and bridges the gap between RWD-derived clinical research and clear patient outcomes, providing a more comprehensive understanding of how the device(s) are impacting patient care. Enhancing Post-Market Clinical Follow-up (PMCF): By integrating RQM+'s regulatory strategies with 3Aware's RWE platform, the partnership will streamline PMCF activities, reducing operational costs and time for MedTech companies. Data Management and Analysis: Leveraging 3Aware's capability to extract and analyze complex real-world data, the collaboration will enhance the decision-making process, supporting regulatory submissions and surveillance activities. Global Compliance and Market Access: With RQM+'s insight into global regulatory requirements and 3Aware’s technology, the partnership will facilitate faster and more efficient market access for medical devices across various international markets. "This partnership is a testament to our commitment to driving healthcare innovation through regulatory excellence and streamlined data analysis," added Amelia Hufford, PhD, SVP of Clinical & Regulatory Science Operations at 3Aware. "By combining our strengths, we are setting a new standard in the MedTech industry." About 3Aware 3Aware created a fit-for-purpose analytic platform for the MedTech industry, combining data science and clinical science, to automate highest-quality clinical real-world evidence for Post-Market Clinical Follow-up (PMCF), Label Expansion, Marketing Assertions and more. 3Aware integrates real-world data sources such as EHRs and processes vast amounts of patient data, transforming the data into easily assessed patient outcome information. 3Aware pinpoints specific devices via UDI numbers and provides access to full patient EHR records, including unstructured notes. 3Aware enables MedTech companies to find longitudinal data for Class III implants and procedure-specific clinical evidence for label expansion opportunities. 3Aware reduces time and resources dependency, thus accelerating study timelines.  Please visit 3aware.ai for more information. About RQM+ RQM+ is a leading MedTech service provider accelerating compliance and market success. Through unparalleled expertise and industry knowledge, RQM+ delivers specialized solutions and expedites the journey along the full product lifecycle for medical device and IVD companies, from concept to commercialization to post-market. The RQM+ portfolio of services enables the delivery of end-to-end solutions across the complete product lifecycle: Regulatory and Quality Consulting Lab Services and Materials Consulting via Jordi Labs Clinical Trials Reimbursement ai (AI/ML Platform) Please visit rqmplus.com for more information. #### John Potthoff Joins RQM+™ as CEO PITTSBURGH, May 9, 2024 – RQM+, a leading global MedTech contract research organization (CRO), today announced John Potthoff, Ph.D., as its new CEO. This transition comes as former CEO, Margaret Keegan, announced she plans to move out of day-to-day operations to focus on her role as an operating partner with Linden Capital Partners. Margaret will remain on the board of RQM+. John, co-founder and former CEO of Elligo Health Research®, has been on the RQM+ board since 2021. He brings extensive MedTech industry expertise to his new role as CEO of RQM+. Prior to Elligo, he was CEO of Theorem Clinical Research, which had a significant global med device and diagnostics business unit, and was also the chief operating officer at INC Research. “During Margaret’s tenure, she completed three acquisitions and made significant progress in creating an end-to-end MedTech CRO at RQM+,” John said. “I look forward to building on this remarkable foundation and continuing to drive growth and advance global healthcare through MedTech innovation.” As a board member of RQM+, Margaret will continue to assist the company in executing its core priorities. “I am extremely proud of the RQM+ team's many accomplishments,” she said. “While I’ll be stepping away from day-to-day operations, I look forward to continuing to support the company. I believe John is a proven leader and is very knowledgeable about the company and our industry. He is well-positioned to lead and enhance RQM+ to meet the ever-changing MedTech industry needs now and into the future.” About RQM+ RQM+ is a leading MedTech service provider offering consulting, clinical trial, lab, and reimbursement services, as well as technology solutions to support the entire product lifecycle. RQM+’s global team of clinical, technical, and industry experts push the boundaries of excellence. With former FDA, Medicines, and Healthcare Products Regulatory Agency (MHRA) and notified body regulators, RQM+ has deep expertise in all clinical specialties. We reduce commercialization risk by offering a full complement of CRO services to progress medical devices, digital therapeutics and diagnostics onto the market and keep them there. In addition to early- and mid-stage MedTech companies, we currently work with 19 of the top 20 medical device manufacturers and seven of the top 10 IVD companies. #### Leadership Appointments at RQM+ PITTSBURGH, August 27, 2024 – RQM+, a leading global MedTech service provider (CRO), today announced leadership appointments for Ronnie Mahofski and Kevin Rowland, both to Executive Vice President and General Manager. Mr. Mahofski will be leading the companies Consulting Services and Fern.ai business units. Mr. Rowland will lead Jordi Labs, an RQM+ company. “These strategic appointments reflect RQM+'s dedication to returning to the fundamentals that have made us pioneers in the industry. We are confident that Ronnie and Kevin's leadership will further our mission of bringing innovative, safe, and effective medical technology to the patients who need it,” John Potthoff, Chief Executive Officer. In his expanded role, Mahofski will oversee the regulatory and quality consulting services and the corresponding business development team, as well as tech enablement efforts with Fern.ai. Ronnie joined the RQM+ team in 2015, excelling in key roles within Business Development and serving as Head of Mergers and Acquisitions. Kevin Rowland has been an integral part of Jordi Labs for nearly 15 years, serving as team leader for the GCMS and LCMS groups, as well as Laboratory Manager and Director of R&D. His expertise includes the interpretation of high-resolution accurate mass MS data for identifying non-target, unknown compounds. In his new role, Kevin provides exceptional service to Jordi Labs' customers and ensures the safety of products for patients in need. About RQM+RQM+ is a leading MedTech service provider offering consulting, clinical trial, lab, and reimbursement services, as well as technology solutions to support the entire product lifecycle. About Jordi Labs, an RQM+ CompanyJordi Labs, an RQM+ Company, provides the highest quality contract analytical services to some of the world’s leading consumer products, polymers, pharmaceutical and medical device manufacturers. Our team of PhD analytical chemists specialize in chemical identification. One of core competencies is Extractables & Leachables testing. About Fern.aiFern.ai, an RQM+ Company, is a life sciences-focused AI / ML platform to empower clients to seamlessly manage compliance requirements and efficiently navigating the dynamic regulatory landscape. Fern.ai is the only comprehensive platform designed to enhance the entire MedTech lifecycle to deliver quality, speed to market, and compliance from concept to commercialization. #### RQM+ Appoints Ross D. Segan, MD, MBA, FACS, to Board of Directors Former FDA and Johnson & Johnson leader brings deep clinical, regulatory, and enterprise strategy expertise to “The MedTech CRO.” PITTSBURGH; Jan. 8, 2026 (Business Wire) – RQM+, a leading global MedTech service provider (CRO), today announced that Ross D. Segan, M.D., MBA, FACS, has joined its board of directors. Dr. Segan is a physician–executive and MedTech strategist with senior leadership experience at the U.S. Food and Drug Administration (FDA), Johnson & Johnson, Olympus, Covidien, and Vensana Capital, and currently serves as CEO of Medical Scientific Advisors, LLC. “Dr. Segan’s leadership at the intersection of clinical practice, regulatory science, and global MedTech innovation is unmatched,” said John Potthoff, Ph.D., chief executive officer of RQM+. “His experience advising regulators, industry leaders, and investors will strengthen RQM+’s ability to help clients navigate complexity and deliver high-impact products to market.” “RQM+’s clear sense of purpose and respect for the trust placed in our industry by patients and regulators drew me to the board,” said Dr. Segan. “I look forward to contributing my experience to a company that sees quality and regulatory excellence as enablers of lasting impact.” Michael Farah, partner at Linden Capital, said, “At Linden, we invest in leadership and governance to drive long-term value, and Dr. Segan exemplifies that approach. His experience across clinical care, regulation, and enterprise strategy will be a strong asset as RQM+ continues to scale its platform and impact.” Dr. Segan’s career spans 20+ clinical specialties and global markets, with a consistent focus on aligning clinical outcomes, regulatory strategy, health economics, and reimbursement to unlock commercial value. He is also active in policy and advocacy through work with AdvaMed and other industry organizations. About RQM+ RQM+ is a leading MedTech service provider offering consulting, clinical trial, lab, and reimbursement services, as well as technology solutions to support the entire product life cycle. About Jordi Labs, an RQM+ Company Jordi Labs, an RQM+ company, provides high quality contract analytical services to some of the world’s leading consumer product, polymer, pharmaceutical, and medical device manufacturers. Our team of Ph.D. analytical chemists specializes in chemical identification. One of our core competencies is extractables & leachables testing. #### RQM+ Launches SMART Solutions Life Cycle Partnership Model PITTSBURGH; March 12, 2026 – RQM+, a leading MedTech CRO offering regulatory consulting, clinical trial, laboratory, and reimbursement services, today announced the launch of SMART Solutions, a life cycle partnership model designed to help medical device and diagnostics companies manage growing regulatory and development complexity.  SMART Solutions introduces a strategy-led operating framework that unifies regulatory, quality, clinical, reimbursement, and laboratory expertise to support MedTech companies across the entire product life cycle to help reduce risk from early development through post-market.   “MedTech companies are navigating unprecedented complexity as regulatory expectations evolve, product innovation accelerates, and post-market expectations are expanding,” said John Potthoff, Ph.D., chief executive officer of RQM+. “SMART Solutions moves beyond traditional consulting by providing an integrated life cycle partnership that helps sponsors gain earlier clarity, reduce risk, and execute complex programs more predictably. This solution makes RQM+ one of the few MedTech CROs that can truly integrate device, software, lab, and regulatory strategy end to end.”  SMART Solutions addresses these challenges by replacing fragmented vendor-by-vendor workstreams with a coordinated life cycle model delivered through engagement options:  Integrated SMART Solutions for small to midsize enterprises: Governed life cycle partnership integrating regulatory, clinical, quality, reimbursement, and lab services  Functional SMART Solutions for larger enterprises: Targeted functional support within the framework  The model is designed for complex device programs and high-growth therapeutic areas, such as cardiovascular and neurology, as well as advanced product categories, including implantable devices, combination products, software-enabled technologies, and IVD companion diagnostics.  The framework also leverages RQM+’s growing clinical and laboratory capabilities, including Jordi Labs, an RQM+ company specializing in analytical chemistry and extractables and leachables testing, as well as AI-enabled technology platforms that are supported by proprietary analytical data.  By integrating regulatory strategy, clinical development, and lab science within a single operating model, RQM+ helps device and diagnostics companies accelerate development timelines, while improving life cycle governance and scalability.  MedTech companies can learn about SMART Solutions or request a life cycle consultation.  About RQM+ RQM+ is a leading MedTech service provider offering consulting, clinical trial, lab and reimbursement services, as well as technology solutions to support the entire product life cycle.  About Jordi Labs, an RQM+ Company Jordi Labs, an RQM+ company, provides contract analytical services to leading consumer products, polymers, pharmaceutical, and medical device manufacturers. The company’s Ph.D. analytical chemists specialize in chemical identification, including extractables and leachables testing.   #### RQM+™ Launches Fern.ai™ Smart Authoring Module for MedTech PITTSBURGH, May 20, 2024 – RQM+, a leading MedTech service provider, is proud to announce the launch of the Fern.ai Smart Authoring module. The groundbreaking Fern.ai platform now includes Smart Authoring in addition to Systematic Literature Review. Together, these modules are set to transform the landscape of regulatory documentation for MedTech, enhancing compliance, accuracy, and efficiency. As the MedTech sector evolves, regulatory demands grow increasingly complex. Fern.ai's Smart Authoring module is designed to meet these challenges head-on, offering an intelligent solution that automates and streamlines the creation, management, readiness, and ongoing maintenance of regulatory documents. Key Features and Benefits: Single Source of Truth: Smart Keys and product profiles provide a single source of truth with version control and common terminology and style Template Management and Alignment: Readily update content within the product profile and populate product information across templates automatically Dynamic Linking Across Documents: Smart Keys readily adapts to content changes and enables collaboration across authors Enhance Team Collaboration: Provide access to cross-functional users for in-platform comments and editing Streamline Literature Reviews: Conduct your literature reviews in Fern.ai and add outputs directly into your product documentation via Smart Authoring integration Fern.ai Smart Authoring addresses the critical need of speed and accuracy for regulatory documents in preparation for submissions, helping manufacturers reduce time-to-market for their innovative products. By automating repetitive tasks and ensuring consistency across regulatory documents, the platform allows teams to focus on higher-value activities, ultimately driving greater efficiency and innovation within the organization. "Fern.ai’s Smart Authoring module represents a significant leap forward for the medical device industry," said John Potthoff, CEO of RQM+. "By harnessing the power of AI and automation, we're not only simplifying the creation, management, and maintenance of regulatory documentation but more importantly, it enables manufacturers to bring life-saving devices to market faster and with greater confidence. This platform is a game-changer for regulatory affairs professionals and the MedTech industry as a whole." With the launch of Fern.ai’s Smart Authoring module, RQM+ reaffirms its commitment to innovation and excellence as a MedTech service provider. Based on the proven AI expertise of our instrumental development partner Giotto.ai, the Smart Authoring module paves the way for a more efficient and compliant future in MedTech. For more information about Fern.ai Smart Authoring, visit Fern.ai. About RQM+RQM+ is a global MedTech service provider focused on accelerating compliance and market success. Through our unparalleled expertise and industry knowledge, we deliver specialized solutions and expedite the journey along the full product lifecycle for Med Device and IVD companies, from concept to commercialization to post-market. Our portfolio of services enables the delivery of end-to-end solutions across the complete med device product lifecycle, with our: Regulatory and Quality Consulting Lab Services (Jordi Labs) Clinical Trials Reimbursement Technology Solutions Media ContactRonnie Mahofski, +1 (412) 816-8105, rmahofski@rqmplus.com #### We Don’t Make MedTech — We Make MedTech Happen: Introducing the New RQM+ Brand Identity At RQM+, we don’t build medical devices. We don’t invent life-changing diagnostics. We don’t create combination products.  We don’t make MedTech — We make MedTech happen.  RQM+ is the leading MedTech solutions partner and accelerates the product lifecycle from innovation to patient impact. While manufacturers create MedTech, we add expertise, bringing regulatory experience, operational execution, leading laboratory and materials science, quality and clinical expertise, and end-to-end know-how to drive products from concept to post-market. Our expert services span numerous therapeutic areas and device types. Whether it's regulatory strategy, clinical trials, lab testing, or reimbursement support, we collaborate with manufacturers to deliver end-to-end MedTech solutions that bring life-changing products to patients: faster, safer, better. We're thrilled to introduce the new RQM+ brand identity that more accurately captures the essence of what we do, how we do it, and why it matters. Our tagline, Evolving MedTech, reflects our commitment to advancing the industry by transforming processes, accelerating timelines, and improving outcomes for both manufacturers and patients. We accelerate innovations to reach patients faster, safer, and with measurable impact. Yet our identity goes beyond our tagline, reflecting our purpose, passion, and commitment to our clients and their patients. We make MedTech happen through: Tailored consulting services Fast-tracking clinical success Gold standard laboratory testing and material analysis Expert reimbursement services Why the refresh? The MedTech industry is constantly evolving. As a key industry leader, we help companies bring lifesaving devices, IVDs, and combination products to market with speed and compliance. Our refreshed brand reflects our impact: empowering innovators with the expertise, strategy, and execution needed to navigate regulations, accelerate approvals, and ensure patient safety. What’s changing?  While our core values and commitment to excellence remain the same, we've evolved our visual identity, messaging, and partner engagement: A Clearer, More Distinct Voice: Our messaging highlights the results we achieve, helping MedTech companies turn innovations into reality. A Bold and Confident Look: Our modernized design reflects our industry leadership and forward-thinking approach. Stay tuned for our new website soon! Stronger Engagement Across Platforms: Experience our brand story through compelling content, continued thought leadership, and a deeper connection with the MedTech community, including our employees’ personal narratives. Let’s Make MedTech Happen. Together!  Join us as we push the boundaries of what’s possible in MedTech. Stay tuned for more updates, impact stories, and insights. Here's a short video highlighting the ways our employees make MedTech happen. [NEED VIDEO] About RQM+ RQM+ is the leading MedTech solutions partner, accelerating the product lifecycle from innovation to patient impact. We provide the expertise, delivering regulatory experience, operational execution, leading laboratory and materials science, clinical and quality expertise, and end-to-end know-how to drive products from concept to post-market. With specialized services spanning numerous therapeutic areas and device types, RQM+ collaborates with companies to navigate complex regulations, accelerate approvals, and ensure patient safety. Whether it’s regulatory strategy, clinical trials, laboratory testing, or reimbursement support, our comprehensive solutions help deliver life-changing medical technologies to patients — faster, safer, and with measurable impact. RQM+ delivers results through: Regulatory and Quality Consulting: Expert guidance to navigate global regulations, including FDA submissions, CE marking, MDR/IVDR compliance, and post-market support. Clinical Trials: Comprehensive trial management that ensures safety, efficiency, and compliance from study design to execution. Laboratory Services via Jordi Labs: Gold standard testing and materials analysis trusted by the FDA and industry leaders. Reimbursement Solutions: Customized strategies that help medical technologies gain market access and reach patients. AI/ML Technology: Advanced platforms that automate compliance documentation, delivering up to 50% efficiency gains. With over 40 years of experience and a global team of industry leaders — including former regulators from the FDA, MHRA, and Notified Bodies — RQM+ has partnered with 19 of the top 20 medical device companies and 7 of the top 10 IVD companies. With a proven track record of success, RQM+ enables companies of all sizes to bring innovations to market faster, safer, and with greater confidence. ### Resource #### 7 Reimbursement Strategy Gaps Your MedTech Needs to Bridge Why Regulatory Clearance Doesn’t Guarantee Medical Device Reimbursement  Most MedTech companies design trials to clear the regulatory bar, only to find that payers need different evidence entirely. The result is a device that is approved but not covered, perhaps stalled between clearance and the market it was built to reach.  This infographic identifies the 7 reimbursement strategy gaps most likely to block adoption, explains what payers say when they encounter each one, and shows what a payer-ready study design looks like instead.  The 7 Gaps That Stall Devices Between Approval and Adoption  Regulatory-only trial design   Missing economic endpoints   Weak comparator strategy   Siloed planning   No operational evidence  Unclear value story   Late reimbursement planning  Closing these gaps requires health economic evidence built into your study design from the start, rather than added after the submission is filed.  Download the infographic for the complete gap analysis, payer response examples, and a measurement guide covering devices, diagnostics, and SaMD.  #### A Guide to Smarter E&L Testing & ISO 10993-18 Compliance How Predictive Modeling and Risk-Based Strategy Are Changing What “Defensible” Means ISO 10993-18 expectations are evolving faster than most extractables and leachables (E&L) programs. The approach that was defensible when you started may not hold up by the time it reaches a reviewer. Programs that meet the minimums but lack scientific rigor are encountering new questions about identification confidence, quantification accuracy, and documentation rationale.¹  This guide is built on patterns observed across hundreds of E&L studies annually at Jordi Labs, an RQM+ company. It shows where programs are most likely to be challenged and how to close those gaps before they become delays.  What You’ll Learn What changed in ISO 10993-18:2020 and why regulatory interpretation continues to evolve beyond what the standard captures (e.g., shifting USP chapter expectations²˒³ and FDA interpretations based on submission patterns4) How predictive response factor modeling, including Lumo™, uses neural network models to identify unknowns faster5 When predicted response factors can replace empirical standards, and when they cannot How to build documentation that answers regulatory questions on AET calculation, identification confidence, and method selection A self-assessment framework to identify misalignment with current expectations Who This Is For QA/RA leaders, biocompatibility specialists, and toxicologists responsible for ISO 10993 compliance and E&L program strategy.  References  International Organization for Standardization. (2020). ISO 10993-18:2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process. https://www.iso.org/standard/64750.html  United States Pharmacopeia. (2023). USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems. https://doi.usp.org/USPNF/USPNF_M7126_03_01.html  United States Pharmacopeia. (2023). USP <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems. https://doi.usp.org/USPNF/USPNF_M7127_03_01.html  U.S. Food and Drug Administration. (2023). Use of International Standard ISO 10993-1. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and  Deng, Y., Grice, A., Louis, M., et al. (2026). Neural Network Prediction of Response Factors for Extractables and Leachables in Pharmaceuticals and Medical Devices. PDA Journal of Pharmaceutical Science and Technology. https://journal.pda.org/content/early/2026/01/30/pdajpst.2025-000061.1  #### A New Era of LDT Oversight: Adapting to FDA Regulations Laboratory Developed Tests (LDTs) in the U.S. are currently at a pivotal moment. Traditionally, these tests have been under enforcement discretion, but the FDA is now proposing significant regulatory changes. Over the next five years, the FDA aims to phase out this discretion, introducing a framework that requires comprehensive submissions from LDT providers. This move aligns with the recent EU IVDR implementation, which brought similar oversight to LDTs and all In Vitro Diagnostics (IVDs) in Europe. Interestingly, the U.S. proposal has already generated substantial feedback, with over a thousand comments submitted, many expressing opposition to the new regulations. The panel explores the following critical aspects of this evolving regulatory landscape: Impact Assessment: We'll explore the potential repercussions of the U.S.'s proposed LDT regulations. Regulatory Timeline: Gain insights into the rule-making process and the expected timeline for implementation. EU's Response: Learn how companies in the EU have adapted to increased oversight of LDTs. Preparation Strategies: Discuss proactive measures that can be taken in anticipation of these changes. Challenges Ahead: Identify the major hurdles companies might face during this transition. Market Dynamics: Evaluate whether this represents an opportunity for IVD manufacturers to expand their market share, especially as smaller labs grapple with meeting the FDA's new expectations. This session promises to be an enlightening exploration of the future of LDT regulation and its impact on the MedTech industry. Please watch now by completing the form. Panelists: Nancy Morrison, RAC – Vice President, Intelligence & Innovation Margot Borgel, Ph.D. – Director, IVD Intelligence & Innovation Eila Pattee, Principal Consultant Andrew Lakey, Ph.D. – Senior Consultant Theresa Miles – VP, Client Portfolio Management (moderator) #### Adapting to the New LDT Regulatory Reality The FDA's long-awaited Final Rule on Laboratory Developed Tests (LDTs) is here, marking a significant shift in the regulatory landscape for diagnostic testing. Released on April 29th, 2024, and published in the Federal Register on May 6th, this rule brings LDTs under the same regulatory umbrella as other in vitro diagnostic (IVD) devices. The FDA believes this change will better protect patient health and safety by ensuring consistent oversight and quality standards across all diagnostic tests. Join us for an insightful webinar where RQM+ Director for IVD Global Regulatory Affairs, Margot Borgel, and Senior Principal Consultant and IVD expert, Bethany Chung, will dive into the key provisions of the Final Rule, its impact on laboratories, and actionable strategies for successful compliance. They will draw from their deep expertise and discussions at the recent Association of Medical Diagnostics Manufacturers (AMDM) annual meeting to provide you with the most up-to-date insights. In this webinar, you will: Understand the expanded enforcement discretion for certain LDTs, including grandfathering provisions for currently marketed tests Explore the phased implementation approach over four years and key compliance milestones Learn about the explicit classification of LDTs as medical devices and its implications Discover actionable insights and preparation strategies, including compliance readiness, documentation and process improvement, and staff training Gain valuable guidance on navigating the evolving regulatory landscape and ensuring seamless compliance Who should attend: Quality Assurance Managers and Directors Regulatory Affairs Professionals Laboratory Managers and Directors Product Development Teams Clinical Affairs Professionals Compliance Officers Presenters Margot Borgel, Ph.D.Director of IVD Global Regulatory Affairs Margot Borgel, Ph.D. is the Director for IVD Global Regulatory Affairs at RQM+ where she supports our clients in their IVD regulatory journey and provides technical and regulatory advice through the entire product lifecycle. Prior to RQM+, Margot was a Technical Specialist at BSI, where she performed technical reviews for IVDR, IVDD and UKCA certification. She is especially passionate about certification of high-risk devices and enjoyed seeing these devices through IVDR certification while at BSI. Before her notified body work, Margot worked for Immucor, Inc. where she held roles in R&D, manufacturing technical support and manufacturing. Bethany Chung, Ph.D., RACSenior Principal Consultant Bethany has a Ph.D. in biomedical engineering and loves all things quantitative. She has more than 10 years of experience with medical devices in the clinical space. Prior to joining the regulatory world, she was a clinical researcher specializing in ML and AI-based devices, and she is currently in the Clinical and Post-Market Practice at RQM+. #### Advancing Health Equity with IVDs & Medical Devices Featuring Michelle Tarver, M.D., Ph.D. from FDA, CDRH Live! #81 presentation and panel  |  Recorded 8 August 2024 Available on demand. RQM+ welcomes Michelle Tarver, M.D., Ph.D., Acting CDRH Director and Deputy Center Director for Transformation, FDA, CDRH, to a presentation and panel discussion aimed at increasing awareness and understanding of equity in the medical device and IVD space. Objectives: Regulatory ExpectationsExamining health equity concerns, regulatory efforts to promote equity, and FDA requirements for enhancing diversity in clinical trials Healthcare at HomeExploring the "Home as a Healthcare Hub" initiative and its implications for health equity, including the challenges and opportunities of integrating healthcare services at home Industry PerspectivesProviding insights from industry leaders on how medical device companies are addressing health equity, with a focus on real-world examples and action plans Action Plans and StrategiesSharing best practices for developing and implementing plans that assess diversity, explore risks, and identify actions to address health equity within medical device companies Interactive Q&AOffering an opportunity for participants to engage with experts, ask questions, and gain a deeper understanding of the topic Complete the form on this page to watch the recording and download the slides. Panelists: Michelle Tarver, M.D., Ph.D. – Acting Director and Deputy Center Director for Transformation, FDA, CDRH Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovations, RQM+ Jon Gimbel, Ph.D. – Vice President of Technical, RQM+ Brandy Chittester – Senior Director, Clinical Operations, RQM+ Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+ (moderator) Certificate of Participation available upon request for live attendees. #### AI in Medical Devices: Practical Adoption for Medical Device Regulatory Teams LinkedIn Live   MedTech regulatory teams used to ask if AI had a place in their workflows. Now, teams are using it, but they’re not sure if they’re using it responsibly, efficiently, and in a way that stands up to regulatory scrutiny.  In this LinkedIn Live, RQM+’s Jai Kutty, VP, Cardiovascular Center of Excellence, leads an expert panel through the practical realities of AI adoption in MedTech regulatory affairs, offering essential insights on everything from day-to-day use cases and validation frameworks to QMS governance and what notified bodies expect to see.  What’s Covered  How regulatory teams are using AI today: Real use cases in regulatory intelligence monitoring, literature review for CERs, and QMS documentation drafting   AI risk boundaries: How to assess AI tool risk based on agency, probability of error, and severity of harm   What notified bodies expect: The minimum QMS requirements for AI use, including vendor management, change control, and competency training records   When AI adds complexity instead of efficiency: The AI mistakes that can derail regulatory strategies, including hallucinated predicates and over-reliance on automated outputs   Proven validation frameworks: How to validate AI tools proportionally, manage model versioning, and know when human oversight is nonnegotiable   Privacy and PII safeguards: Practical approaches to protecting patient data when using LLMs   The EU AI Act: What deployer responsibilities mean for MedTech manufacturers using AI in regulated processes  Who This Is For  Regulatory affairs professionals, QA/RA leaders, and clinical teams at medical device and IVD companies who are actively exploring or expanding AI use in their regulatory workflows and want a framework for doing it defensibly.  #### AI Meets Regulation ⏺️ Recorded October 30, 2025 The EU Medical Device Regulation (MDR) already sets strict requirements for safety, performance, and clinical evidence. Now, with the EU AI Act entering the stage, manufacturers face a new layer of obligations around transparency, risk management, and ethical use of AI in medical technologies. In this live webinar, experts from DQS and RQM+ are joining forces to demystify the intersection of MDR and the AI Act. Speaker bios:Chris A. Parr, PMP – Principal Consultant on Regulatory Affairs at RQM+ Chris Parr is a seasoned regulatory leader with 20+ years in the MedTech and pharmaceutical sectors. With a background in natural sciences, he offers deep expertise in regulatory affairs, quality management systems, risk management, design controls, and project management. He has led global teams, delivered complex projects in both industry and consulting, and is highly skilled in implementing the EU MDR and other EU legislation. Chris has worked directly with major regulatory bodies, including the US FDA, Health Canada, EU Competent Authorities, and Notified Bodies. Dr. Andrei Ninu – Head of Software Operations at DQS Andrei Ninu is a top-performing Product R&D professional with 15+ years of experience driving innovative, revenue-generating solutions in biomedical engineering. He has led products through the full lifecycle—from concept and prototyping to manufacturing, installation, and final commissioning—while excelling in research, clinical and feasibility studies, and process improvement. Andrei combines technical expertise with strong business acumen, conducting cost analyses, evaluating market segments, and shaping effective business and marketing strategies. Certificate of attendance available upon request for live attendees. #### Aligning Your QMS with the FDA's QMSR Updates In February 2026, the FDA new Quality Management System Regulation (QMSR) will become effective. This represents the most significant change since the implementation of design controls in 1996 and is aimed at aligning the U.S. regulations more closely with global standards, particularly ISO 13485. What does this mean for manufacturers and why is it vital to get ahead of it? Join us for an insightful 45-minute webinar (including Q&A) where RQM+ Vice President of Intelligence & Innovation, Nancy Morrison, RAC will dive into the upcoming changes. Understand the critical updates, from design controls and risk management to traceability and record-keeping requirements. Discover how these changes aim to streamline processes, enhance device safety and performance, and foster a more global alignment in quality management practices. Whether your organization is currently ISO 13485 compliant or facing a significant overhaul of your quality management system (QMS), our session is designed to provide you with the knowledge and strategies to assess the impact, plan effectively, and implement the necessary changes efficiently. We'll also explore the unchanged elements of the regulations to give you a comprehensive understanding of the landscape post-2026. By attending, you'll gain: A clear understanding of the new QMSR requirements and their implications for your business. Insight into how to compare your current QMS with the revised requirements and identify key areas for action. Strategies for quality planning, executing updates, and ensuring compliance through practical examples and expert guidance. Opportunities to ask your questions and interact with industry peers facing similar challenges in the webinar chat. Don't miss out on this opportunity to prepare your team for a smooth transition to the new regulatory environment, ensuring continued compliance, and maintaining the highest standards of quality and safety for your medical devices. Please complete the form to watch the recording and download the slides. Presenters Nancy Morrison, RACVice President, Intelligence & Innovation Nancy has over 30 years of quality and regulatory experience in the medical industry with US and global regulatory submission experience. The last eleven years have been with RQM+ working with start-up, mid-size, and multi-national medical device and combination product companies. Nancy has a Bachelor of Science in Mathematics and an Advanced Certificate in Regulatory Affairs along with RAC certifications for the US and EU. Nancy has been providing FDA, EU MDR, and IVDR leadership in developing solutions and implementing the regulations at small and large organizations. Melissa DeHassPrincipal Consultant Melissa holds a BSc in Biology, a certificate in Regulatory Compliance, and an MBA. She has worked for over 20 years in medical devices and pharmaceuticals. Melissa has worked across the product life cycle, from development to post-market. She has proven cross-functional experience and uses this skillset to support new product development and assess design changes from regulatory and quality perspectives. She has written regulatory strategies, 510(k)s, a PMA supplement, NDA supplements, a breakthrough designation and technical files. She has experience with QMS development and improvement, and with supporting a company through ISO certification. Melissa is a certified internal lead auditor and has conducted internal and supplier audits as well as hosted FDA and Notified Body audits. Through her experiences working for small medical device manufacturers, Melissa takes a business-balanced approach to regulatory and quality. Further reading - Brought to You by the Letter M: Operational Considerations for Transitioning From the QSR to the QMSR & One Year Countdown: Preparing for the FDA’s QMSR Implementation #### Answering the Tough Questions: What Innovators Really Want to Know About Partnering With a Specialized MedTech CRO Direct Answers to the Questions Executives Actually Ask  The standard CRO model is no longer working for MedTech innovators navigating constantly shifting regulations and rising clinical complexity. Missed timelines, poor communication, and teams that don’t understand device-specific risk are frustrating and expensive. This sheet gives you direct, transparent answers to the six hardest questions executives ask when evaluating a specialized MedTech CRO.  What’s Inside  Why lack of ownership (not expertise) is the most common failure in CRO relationships, and what a different model looks like in practice  How upfront regulatory alignment prevents the delays and rework that make “lower-cost” CROs the more expensive choice  How RQM+ SMART Solutions provide the integrated scale of a global partner with the technical precision of a specialized MedTech CRO  Why integrated lab science and medical device regulatory consulting services produce submittable toxicological risk assessments   How mid-program transitions are managed to maintain continuity without sacrificing timeline or quality  Who This Is For Founders, CEOs, and heads of regulatory, clinical, and quality affairs at MedTech companies evaluating CRO partnerships or considering a transition from their current provider.  The most expensive regulatory path is the one you have to walk twice. This resource helps you avoid it.  #### Are We Equipped to Handle a PFAS-Free Future? In an era where sustainability meets innovation, the medical device, and in vitro diagnostics (IVDs) industry faces one of its most significant challenges yet: transitioning away from per- and poly-fluoroalkyl substances (PFAS). With approximately 15,000 chemicals in the PFAS family affecting everything from material sourcing to product design and regulatory compliance, the question looms large—Are we equipped to handle a PFAS-free future? Unveiling Insights by Dr. Jaishankar Kutty RQM+ proudly presents a comprehensive white paper by Dr. Jaishankar Kutty, a leading voice in the field, addressing the impending supply chain and regulatory issues associated with PFAS phase-out. Dive into an in-depth analysis covering: The critical role of PFAS in medical device manufacturing The impact of regulatory changes and supply chain disruptions Strategic approaches for a smooth transition to PFAS-free alternatives Why This White paper Is a Must-Read: Regulatory Insight: Understand the implications of the EU's proposed REACH restriction and the US's regulatory landscape. Supply Chain Strategies: Explore solutions for the imminent challenges posed by major suppliers like 3M discontinuing their PFAS portfolio. Innovation and Safety: Learn about alternative materials that maintain the integrity, safety, and performance of medical devices. The journey towards a PFAS-free future is complex but navigable with the right knowledge and strategies. Fill out the form on this page to access this essential white paper and equip your team with the insights needed for a seamless transition. MEET THE AUTHOR:  Dr. Jaishankar Kutty, Vice President, Global Regulatory Affairs at RQM+ Jaishankar is an eclectic combination of significant EU notified body experience (as a lead technical and clinical reviewer at BSI) and practical industry experience in design and development of cardiovascular devices. Currently, he is focused on assisting medical device manufacturers, in a clinical-regulatory strategic leadership role at RQM+. He helps the RQM+ team find practical solutions in all areas of clinical evidence, biological safety, and EU regulatory strategy. His core competencies span medical device design, pre-clinical model development and biological safety evaluations, advanced biomechanical testing, biomaterial science and chemical characterization, cell biology and tissue engineering, and clinical evidence synthesis and analysis.  #### Behind the Scenes with BSI Head of IVD Notified Body, Alex Laan If you have ever thought to yourself "I wonder what the notified body is thinking?" ...this is a conversation you want to hear. The involvement of notified bodies under the previous IVD directive was limited to a small number of analytes and device types. As a result, many IVD manufacturers have never worked with a notified body and are now trying to understand how notified bodies operate and navigate the complex path towards IVDR certification. In this conversation, Margot Borgel, RQM+ Director of IVD Global Regulatory Affairs, sits down with Head of IVD Notified Body at BSI, Alex Laan. The conversation will explore the inner workings of an IVDR notified body and shine light on how the notified bodies work with other key stakeholders, set expectations for manufacturers, and navigate the constantly changing landscape of IVDR. By attending this free event, you will gain an understanding of how the notified body operates, which will allow more confident and informed interactions as you move through IVDR certification and beyond. The discussion will include: How notified bodies interact with competent authorities and other notified bodies How new guidance and changes to IVDR are implemented within the notified body How expectations are set and consistency is maintained for IVDR certification What notified bodies wish manufacturers knew Watch on demand by completing the form on this page. PARTICIPANTS Alex LaanHead of IVD Notified Body, BSI Alex Laan recently joined BSI as the Head of IVD Notified Body. In this position, Alex will be focusing on further strengthening the regulatory foundations within the IVD team and make BSI future-proof for the years to come in the challenging regulatory environment in the EU for IVD’s.  Alex is originally a biochemical engineer and worked on the design and development of ELISA based assays in virology and immunohematology tests. He has worked a technical specialist in reagents and tests at Sanquin blood bank located in Amsterdam.  He holds degrees in Biomedical Chemistry, Biotechnology and Business Administration. Margot BorgelDirector of IVD Global Regulatory Affairs, RQM+ Margot Borgel, Ph.D. is the Director for IVD Global Regulatory Affairs at RQM+ where she provides her expertise in IVDR implementation and notified body requirements. Prior to RQM+, Margot was a Technical Specialist at BSI, where she performed technical reviews for IVDR, IVDD and UKCA certification. She is especially passionate about certification of high-risk devices and enjoyed seeing these devices through IVDR certification while at BSI. Before her notified body work, Margot worked for Immucor, Inc. where she held roles in R&D, manufacturing technical support and manufacturing. #### Beyond EtO: New EPA Regulations and Sterilization Alternatives The recently finalized EPA rule on ethylene oxide (EtO) emissions requires significant changes for sterilization facilities, potentially impacting manufacturers of sterile medical devices. Listen to our expert panel to understand the implications of these new regulations and discover actionable strategies to explore potential mitigation activities. In this comprehensive discussion, our experts will cover: Impact Assessment: A detailed analysis of the new EPA rule, including how it affects EtO sterilization facilities and manufacturers of sterile medical devices. Compliance Strategies: Guidance on softening EtO cycles to support the effort of reducing EtO emissions and ensuring compliance within the 2-3 year timeline. Alternative Sterilization Methods: An overview of viable alternatives such as Vaporized Hydrogen Peroxide (VHP), radiation, and more. We will discuss their pros and cons, regulatory requirements, and validation processes. Quality and Regulatory Support: Insights into design quality engineering, manufacturing quality engineering, regulatory change impact assessments, and more. Industry Perspectives: An examination of feedback from industry stakeholders and how companies are adapting to these changes. Who Should Attend: This panel discussion is ideal for regulatory affairs professionals, quality engineers, manufacturing leaders, and medical device manufacturers who rely on EtO sterilization or are considering alternative methods. By attending this event, you will gain a clear understanding of the new EtO regulations, learn practical steps to mitigate for compliance-led changes at your sterilization facilities, and explore alternative sterilization methods to ensure your products remain safe and market-ready. Please complete the form to watch the recording and download the slides. Panelists: Jessica Dreyer – Senior Consultant, RQM+ Gregory Murdock – Senior Manager, RQM+ Jon Gimbel, Ph.D. – Vice President of Technical, RQM+ (moderator) Certificate of Participation available upon request for live attendees. More reading - Future-Proofing Sterilization: Understanding EPA’s New EtO Standards and What To Do Now #### Beyond Indications: Managing Off-Label Use for Safety and Compliance This panel discussion is all about navigating off-label use and implementing strategies to improve medical device safety. As we all know, ensuring the safety and efficacy of medical devices is critical to protecting patients and minimizing risks to healthcare providers. However, one of the key challenges manufacturers face is how to identify and handle off-label use, especially with the transition to MDR 2017/745. During the discussion, our experts in device development, regulatory compliance and clinical evaluation shared insights on how to manage off-label use, reduce indications, define indications and contra-indications, as well expand indications using real-world data from post-market surveillance. We dove into the complexities of post-market surveillance and the importance of PMCF data in identifying off-label use. We also explored strategies for optimizing regulatory efforts while maintaining patient safety. Key questions for our audience include: Have you had to restrict or reduce the indications for your device as part of the transition to MDR 2017/745? Are you struggling to define your indications and contra-indications for your device? Have you started to see examples of off-label use cropping up as your PMCF data comes back in? Are you trying to expand your indications using real-world data from post-market surveillance? Are you struggling to handle instances of off-label use within your risk management process? Our panelists provided valuable insights into these questions and more! Panelists: Dr. Tom Melvin, Associate Professor of Medical Device Regulatory Affairs - Trinity College Dublin (former HPRA) Amie Smirthwaite, BEng, Ph.D. – Senior Vice President, Intelligence & Innovation - RQM+ Dr. Sally Sennitt, Medical Director, Intelligence and Innovation - RQM+ Ed Ball, Manager, Intelligence and Strategic Execution - RQM+ #### Bridging the Real-World Evidence Gap AVAILABLE ON DEMAND This webinar explains the importance and application of Real-World-Evidence (RWE) and aims to help MedTech teams go from ideal frameworks to practical realities. Get clear on the difference between real-world data (RWD) and RWE, including how raw data becomes fit-for-purpose evidence. Learn why RWE matters for decision making and regulatory success, and how to bridge the gap by putting it into practice! You’ll see how traditional and innovative data sources, from surveys and wearables to EHR datasets and claims databases, fit into putting RWE into practice. We'll share real-life case studies and examples, as well as addresses common pitfalls to avoid, including data quality, device identification, follow-up, continuity of care, clinician insight, reporting consistency, and establishing clinical causality. In the end, attendees will leave with clear practical tips and strategies for implementing real-world evidence in their own operations. Who Should Watch Regulatory Professionals Clinical Affairs Professionals Product and Program Managers Health Economics and Reimbursement Professionals Post-Market Surveillance and Safety Managers Learning Objectives How real-world evidence can support medical devices Current methods of acquiring real-world data and their strengths and weaknesses Case study highlighting successful use of real-world evidence to support PMCF Presenters Bethany Chung, PhD, RAC, Director of Technical Solutions and Innovation, RQM+ Amelia Hufford, PhD, SVP, Clinical and Regulatory Science Operations, 3Aware A certificate of attendance is available upon request for live attendees. #### Built for Her: Funding, Fixing, and Fueling the Next Era of MedTech NOW AVAILABLE ON DEMAND Women’s health is finally getting the attention it deserves, yet progress is still slowed by gaps in clinical trial diversity, complex regulatory pathways, and funding challenges. In this RQM+ Live! panel discussion, industry leaders and regulatory experts will share real-world strategies MedTech companies can use to navigate these barriers and bring life-changing innovations to market. Why Attend? Unlock Market Opportunities – Women’s health is one of the fastest-growing MedTech sectors, with rising investor interest and funding. Gain Regulatory Insights – Understand how evolving regulations impact clinical trials, approvals, and commercialization. Learn from Real-World Success – Hear how industry leaders are overcoming challenges and making an impact. Ask Your Toughest Questions – Engage directly with panelists during the live Q&A. Bring Innovations to Market – Get expert insights on bridging clinical research, regulatory approval, and commercialization. Discussion Topics The Business Case for Women’s Health Innovation – Why investors, manufacturers, and regulators are prioritizing this space and what it means for MedTech companies. Clinical Trials and Data Gaps – The urgent need for inclusive research, historical data biases, and evolving regulatory expectations. Regulatory and Market Access Hurdles – Key challenges in securing approval and reimbursement—and how to overcome them. Scaling Women’s Health Solutions – Lessons from industry leaders on funding, partnerships, and commercialization strategies. Who Should Attend? MedTech professionals driving innovation in women’s health Regulatory and quality leaders navigating complex approval pathways Clinical trial specialists improving diversity and data accuracy Investors and strategists seeking insights into funding and market growth R&D and product development teams designing women’s health solutions Healthcare policymakers and advocates shaping the future of women’s health innovation Panelists and moderator: Marissa Fayer – CEO, Her Health Equity & DeepLook Medical Megan Callanan – US & Global Regulatory Lead, Natural Cycles Stephanie Kladakis – Executive Vice President, Chief Technology and Regulatory Officer, AgNovos Bioscience Alexia Haralambous – Senior Principal, RQM+ Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+ (moderator) Certificate of Participation available upon request for live attendees. #### Case Study: Rescuing a Stalled IDE Submission via Advanced Chemical Characterization When Standard Labs Reach Their Limit A MedTech innovator developing a specialized neurological device had exhausted what a commodity laboratory could offer. After one IDE submission with subsequent amendments, the FDA cited major deficiencies: uncharacterized chemicals the original laboratory had been unable to identify. The chemistry reviewer did not accept the chemical analysis due to the volume of unknowns remaining in the report. With a six-month delay looming and investor confidence eroding, the path to clinical trials was seemingly blocked.  This case study shows how Jordi Labs, an RQM+ Company, applied expert-led chemical characterization to resolve the deficiencies that standard medical device testing services could not. It also shows how Jordi’s analytical precision turned a stalled program into an approved IDE and active clinical trial.  What This Case Study Covers Why using a “checkbox” commodity laboratory approach to chemical characterization created compounding FDA deficiencies that threatened the clinical timeline  The value of Jordi Labs applied expert identification to fully characterize unknown substances with a zero-tolerance policy for unresolved compounds  How eliminating unknowns from the chemical analysis gave the chemistry reviewer a complete and defensible profile, enabling IDE approval   Results of the shift from a commodity lab to an expert analytical partner avoided more than six months of projected delays   Who This Is For Regulatory affairs leaders, biocompatibility specialists, and development teams at MedTech companies who work on IDE submissions, chemical characterization deficiencies, or programs where prior laboratory work has left unresolved unknowns.  #### Case Study: RQM+ Partners With Global IVD Manufacturer to Remediate Over 150 IVDR Technical Files URL: https://www.rqmplus.com/resources/case-study-rqm-partners-with-global-ivd-manufacturer-to-remediate-over-150-ivdr-technical-files/ #### Compliance for EU Market Access ⏺️ Recorded September 18, 2025 Manufacturers often focus on MDR or IVDR and miss cross-cutting EU laws that impact CE marking, technical documentation, quality systems, and reporting. As a result, devices may be delayed, blocked from the market, or recalled, and manufacturers may suffer legal penalties and reputational harm. In this RQM+ Live! panel discussion, experts from BSI, Brabners, and RQM+ map how sectoral, horizontal, and national requirements fit together, how notified bodies assess them, and how to build an evidence-based path to EU market access. We will cover practical implications of recent and emerging regulations, including: Batteries Regulation (EU) 2023/1542 AI Act (EU) 2024/1689 Packaging and Packaging Waste Regulation (EU) 2025/40 European Health Data Space Regulation (EU) 2025/327 You’ll learn: About the market surveillance regulation (EU) 2019/1020 and EU Blue Guide. How to identify all applicable legislation for your product and verify coverage. What notified bodies expect to see and the typical level of scrutiny. How to structure your compliance register, QMS updates, and regulatory reporting. Transition timelines and planning tactics to avoid last-minute surprises. Who should attend: Regulatory, quality, clinical, legal, and product leaders responsible for EU market access for medical devices and IVDs. Panelists and moderator: Greg Griffin, PhD, MRSE – Technical Specialist, BSI Claire Burrows – Regulatory Partner, Brabners Chris Parr, PMP – Principal, RQM+ Jaishankar Kutty, PhD – Vice President of Regulatory Affairs, Reimbursement, & Market Access, RQM+ (Moderator) A certificate of attendance is available upon request for live attendees. #### Critical Shifts in Biological Evaluation: Inside the New ISO 10993-1 Risk Management Framework Available on demand. As significant changes to ISO 10993-1 loom on the horizon, manufacturers across MedTech are seeking clarity on what's coming and how to prepare. Join our expert panel for an essential discussion on these upcoming revisions to ISO 10993-1 and their far-reaching implications for biological evaluation processes.  Our panel will provide actionable insights into:  The most significant upcoming changes to ISO 10993-1 and their implementation timeline Comprehensive guidance on applying the ISO 14971 device risk management framework to biological evaluation, including: New approaches to risk estimation Considerations for reasonably foreseeable misuse Practical implementation strategies Critical updates to device categorization and their impact on modified biological effects Strategic considerations for maintaining compliance during this transition  Who Should Attend: This session is essential for regulatory affairs professionals, quality managers, and R&D teams involved in medical device development and biological safety assessment. Whether you're preparing for upcoming changes or seeking to optimize your current processes, this discussion will provide actionable insights for maintaining compliance and efficiency.  Panelists: Taryn Meade – Director of Biological Evaluation Stephen Bond – Senior Toxicologist Amanda DeGraw, MS, Ph.D., DABT – Principal Toxicologist Moderator:  Christine Santagate, RAC – Vice President of Lab Services  Register now to gain critical insights into these industry-shifting changes and ensure your organization is prepared for what the transcript reveals to be "one of the major changes in the standard" - the requirement to apply device risk management to biological evaluation.  Certificate of Participation available upon request for live attendees. #### Electric Brains & Regulatory Pains: Accelerate Neurology Innovation, Slash Risk, & Win Approval NOW AVAILABLE ON DEMAND Neurological devices are rapidly advancing, from AI-driven diagnostics and brain-computer interfaces (BCIs) to transformative implantable therapies for conditions such as Parkinson's, epilepsy, and paralysis. But the path to commercialization involves complex regulatory challenges, clinical trial requirements, and unique ethical considerations. This is especially true as innovations increasingly blend hardware with AI-driven software to bridge biological and artificial neural networks. 🧠 So... how do you bring a neurological device to market without losing your mind? (or your regulatory approval) Join RQM+ experts for an actionable and insightful panel session where you will learn how to: Identify High-Potential Innovations: Pinpoint neurological technologies primed for rapid market uptake, including the critical interplay between hardware and AI-based software devices. Simplify Regulatory Complexity: Clearly navigate FDA and EU MDR requirements, ensuring compliance without unnecessary delays. Manage Ethical and Data Privacy Risks: Tackle head-on the ethical considerations specific to neural devices, including AI integrations and biological data handling. Win Clinical Approval: Deploy strategic clinical trial designs and leverage Real-World Evidence (RWE) effectively, ensuring faster and smoother market entry. This session delivers practical insights to help your organization successfully commercialize innovative neurological products. Who Should Attend Regulatory affairs professionals Clinical trial managers and coordinators Product development leaders and engineers Quality assurance specialists Executives and decision-makers responsible for innovation and commercialization outcomes Learning Objectives Understand key innovations, especially at the intersection of biological and artificial neural networks. Gain clear strategies to streamline FDA and EU regulatory pathways. Identify and mitigate ethical and data privacy challenges unique to neurotechnologies. Learn actionable methods to design and execute successful neurological clinical trials. Panelists and Moderator Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovations Bethany Chung, Ph.D., RAC – Senior Manager, Technical Christine Santagate, RAC – Vice President, Lab Services Jon Gimbel, Ph.D. – Vice President, Technical Certificate of attendance available upon request for live attendees. Further reading - Overcoming Pain-Points in MedTech Clinical Trials for Brain Health Devices #### Enhancing Accuracy in E&L Testing With Machine Learning: Response Factor Prediction for Smarter Decisions The Quantitation Problem at the Heart of E&L Programs Relative quantitation is the standard approach in extractables and leachables assessment (E&L) testing, and for good reason. Formal quantitation of every compound found in a medical device extract is neither cost-effective nor operationally feasible. But relative quantitation carries the inherent limitation of response factor variability. Two compounds at identical concentrations can produce dramatically different signals in mass spectrometry, and without a reliable way to account for that variability, quantitation errors compound into risk assessment gaps. This webinar addresses that problem directly, presenting the science behind Lumo™, Jordi Labs’ machine learning framework for predicting response factors in LC/MS and GC/MS workflows. What You’ll Learn Why mass spectrometry response factor variability creates quantitation errors in E&L programs How Lumo™ uses a multilayer perceptron neural network to predict response factors for LC/MS (positive and negative ion modes) and GC/MS How pre-classification by chemical substructure improves model prediction accuracy, and how built-in flagging keeps expert review in the loop for compounds outside the model’s confident range What the verification data set showed How ML-assisted response factor prediction reduces calibration burden, shortens turnaround time, decreases costs, and improves scientific defensibility across the E&L workflow Who Should Watch Biocompatibility engineers, toxicologists, analytical chemists working with LC/MS or GC/MS, E&L testing specialists, study directors, and regulatory affairs professionals supporting ISO 10993-18 submissions. Lumo™ is a proprietary tool developed by Jordi Labs, an RQM+ company, and is applied within established E&L workflows. The methodology supporting Lumo™ has been published in the PDA Journal of Pharmaceutical Science and Technology.¹ References1. Deng, Y., Grice, A., Louis, M., et al. (2026). Neural Network Prediction of Response Factors for Extractables and Leachables in Pharmaceuticals and Medical Devices. PDA Journal of Pharmaceutical Science and Technology. https://journal.pda.org/content/early/2026/01/30/pdajpst.2025-000061.1  #### EU MDR Timelines and Fine Lines: Unraveling Critical Transition Nuances to Gain Compliance The extension of the EU MDR compliance timeline offers a reprieve for medical device manufacturers, but this extended window comes with its own set of challenges and conditions. As the interim deadlines approach, it’s critical for manufacturers to fully understand their obligations and the ramifications of failing to meet them. In this high-impact panel discussion, thought leaders from a notified body,  manufacturer, and RQM+ come together to unpack the complex landscape of EU MDR compliance in light of Regulation 2023/607 and the transition from MDD/AIMDD to MDR 2017/745. This is a must-attend session for those dealing with legacy device transitions and meeting upcoming MDR deadlines. Topics will include: Understanding key dates: The anatomy of interim deadlines and the conditions for extended transitional arrangements Mastering documentation: What manufacturers need to include in their MDR applications for a successful assessment by notified bodies Staying compliant: Best practices for incorporating the requirements of MDR 2017/745 into existing Quality Management Systems Certificates and self-declarations: Proving the extended validity of your device’s CE certificate and navigating self-declaration protocols Risk management: Avoiding common pitfalls that can delay or derail your transition to MDR compliance A look into the future: How early compliance can give manufacturers a competitive edge and allow for design and market adaptability Attendees will leave the session equipped with actionable insights for navigating this complex regulatory environment, including a deeper understanding of the strategic and tactical steps needed for a successful transition. Panelists: Sharmila Gardner – Technical Documentation Manager & Head of UK Approved Body, Intertek Brian Dahl – Vice President of Quality and Regulatory, Starkey Jaishankar (Jai) Kutty, Ph.D. – Vice President, Intelligence & Innovation, RQM+ Matt Burger – Vice President, Business Development, RQM+ (moderator) #### Exiting PFAS: A Strategic Blueprint for Medical Device Manufacturers With the forthcoming restrictions on Per- and Polyfluoroalkyl Substances (PFAS), medical device manufacturers are on the brink of a significant industry shift. PFAS, known for their versatile properties, have been integral in the production of various medical devices. However, with the phase-out of these substances by the end of 2025, manufacturers must navigate the transition with precision and strategic foresight. This session will begin with a short presentation to set the stage, and will be followed by a panel discussion bringing together RQM+'s leading experts in regulatory affairs, quality assurance, and lab services, to delineate a proactive approach for manufacturers. We will dissect the three-step process required to phase out PFAS used in medical devices, addressing the identification of alternative materials, the intricacies of materials testing and verification, and the critical steps for successful documentation submission to regulatory bodies. Key points of discussion:  Identification of Alternatives: Insights into how manufacturers can identify and source PFAS-free materials for medical devices, including potential redesign considerations.  Testing and Validation: An overview of the materials testing, validation, and documentation process required to ensure compliance and maintain device quality and safety.  Regulatory Strategy: Guidance on the submission of documentation to government agencies such as the FDA, and how to align with global regulatory expectations, including significant changes in the EU.  Strategic Planning: Best practices for project management and ensuring a seamless transition, while minimizing disruptions to supply chains and operations.  Join us as we chart out the roadmap for an industry facing one of its most challenging transitions, ensuring that your devices remain compliant, safe, and on the leading edge of innovation. RSVP by completing the form and we'll email connection details. Panelists:  Jaishankar (Jai) Kutty, Ph.D. – Vice President, Intelligence & Innovation Kevin Rowland – Director of R&D Taryn Meade – Director of Biological Evaluation Consulting James Wrenn – Director of Solutions Delivery Alexia Haralambous – Senior Principal (former FDA) [Newly added!] BONUS: If you want to get the most out of the session, be sure to watch this primer from by Jai beforehand. This video outlines the basics, and we'll dive deeper and answer your questions during the discussion. Further reading - Navigating PFAS Regulations #### FDA's Wound Care Shakeup: Ensuring Your Products Make the Cut The FDA's recently proposed rule on wound care products has sent ripples through MedTech. This rule, if finalized, could significantly impact the classification, labeling, and testing requirements for a wide range of wound care devices. This online panel is your key to understanding the potential implications of this rule on your products and to prepare for the changes.  In this conversation, our team of FDA regulatory experts will examine the proposed rule, providing valuable insights and actionable strategies to help you navigate what's next for wound care devices.  In addition to your questions (please attend live so you can ask!) we'll cover: Impact Assessment: Our experts will break down the key aspects of the proposed rule, including changes to product classification, labeling requirements, and testing. We'll help you determine if your wound care product may be subject to a 510(k) or PMA under the new rule. Our expert panel has extensive experience with FDA submissions and can help you understand what may be needed moving forward. Labeling Implications: We'll discuss the potential impacts on label claims and how they may affect the classification of your wound care product. Our experts will also provide guidance on how to adapt your labeling to ensure compliance with the new requirements. Additional Testing Requirements: We'll explore the potential for additional testing that may be applicable to your wound care product under the new rule. Our experts will provide guidance on how to prepare for and meet these requirements. Industry Feedback: We'll review and discuss the comments submitted by manufacturers, trade associations, and clinical associations during the rule's comment period. Understanding the concerns and perspectives of industry stakeholders will be key in developing effective strategies for compliance. By attending this discussion, you'll gain a comprehensive understanding of the proposed wound care products rule and its potential impact on your business.  You'll walk away with practical strategies and actionable insights to help you ensure compliance, maintain market access, and continue delivering innovative wound care solutions to patients in need.  Please complete the form to watch the recording and download the slides. Panelists: Mark DuVal – President & CEO, DuVal & Associates, P.A. Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovations, RQM+ Jon Gimbel, Ph.D. – Vice President of Technical, RQM+ Erin Gontang – Senior Consultant, RQM+ Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+ (moderator) #### From Crisis to Competitive Advantage: A Strategic Guide to the FDA Warning Letter Response You got an FDA Warning Letter. Now what?   This in-depth guide from RQM+ walks MedTech manufacturers through root cause analysis and systemic QMS remediation to stakeholder transparency and post-warning culture change, outlining real-world strategies that protect operations and strengthen investor confidence.  You’ll learn:  What actions to take in the first 72 hours  How to build a defensible 15-day response  The most common enforcement triggers and how to avoid them  How to manage risk while fixing systems in-flight  What separates tactical failures from successful remediations  RQM+’s value-driving approach to remediation   Who should read:  Quality, regulatory, and executive leaders in MedTech  Product and program owners responsible for compliance  Any MedTech manufacturer facing or seeking to prevent a Warning Letter  Download the white paper to learn how to go beyond triage, build enterprise value, and regain FDA trust.  #### Get Ahead of the Crisis: How Your Quality System Can Prevent Negative Impacts on Customers, Patients, and Reputation No matter our role within MedTech, we all have a responsibility to protect patients. Furthermore, we want our companies to maintain a positive reputation in the market. For these reasons, the best time to exercise your responsibility as a quality and regulatory leader is before the crisis hits. One of the most stressful moments in a working career can be telling a CEO they are about to enter a $40 million recall situation. Avoiding them entirely is best, of course – and this session will cover many of the best ways to do that – but handling them well if they do occur can result in significant savings.   The facts are clear: FDA has increased the number of recalls classified as Class I (most serious), with six so far just four weeks into the new year, setting the pace for another potential record year The EU MDR requires that companies have a Person Responsible for Regulatory Compliance (PRRC), which places specific responsibilities on this leader The costs in dollars, company reputation, and ongoing oversight by regulatory authorities (e.g., consent decree), is in the millions, or even hundreds of millions  In this presentation and panel discussion, we will cover some of the best strategies for preparing for crisis management. More specifically: Taking change control seriously, ensuring proper validation is performed, risk management is updated, and regulatory filings are amended Aggressively evaluating the input and collecting of PMS data, as well as the importance of reacting to it early and consistently Having clear decision points when potentially disastrous patient and business outcomes are possible, with an escalation path that gets organizational attention Regular internal audits and responding to them (and how to give yourself the best chance to catch everything) Preventing future action (withdraw of certification/warning letter/consent decree) by actively making significant quality improvements to company culture and processes  Panelists: Steven Niedelman - Lead Quality System and Compliance Consultant, King and Spalding Scott Edwards - Managing Director, RQM+  Richard Freeman - Director, Global Audit Practice, RQM+  Steve Keverline - Managing Director, RQM+ Theresa Miles - Vice President of Business Development, RQM+ (moderator) #### How AI is Revolutionizing MedTech: Current and Future Applications On Thursday, 23 March 2023, RQM+ and Giotto.ai subject matter experts hosted episode #65 of our Live! show. Artificial Intelligence (AI) has the potential to revolutionize healthcare and the medical technology industry, with the ability to assist in clinical decision-making, improve patient outcomes, accelerate speed to market and improve  efficiency. In this RQM+ Live! show, leaders from RQM+ and Giotto.ai will explore the current and future applications of AI in MedTech, including the use of AI in medical imaging, diagnostics, personalized medicine, remote patient monitoring and medical writing. They will also share their insights on the challenges they've experienced so far in the field, and how AI can help solve some of the hardest problems facing the healthcare industry. This session is designed to be educational and conversational, so please come prepared with questions! The goal of this session is to talk openly and generate ideas about how AI can best benefit you and your organization, now and in the future. We predict companies in the MedTech space who successfully harness AI/ML will have a significant advantage over those that do not. We hope to see you there! Panelists: Alaric Jackson, Chief Digital and Technology Officer – RQM+ Amie Smirthwaite, BEng, Ph.D., Senior Vice President, Intelligence & Innovation – RQM+ Francesco Palma, VP of Product – Giotto.ai Wallyson Oliveira, VP of Machine Learning – Giotto.ai Celeste Maksim, Chief of Staff – RQM+ #### Insider Perspectives: Mastering EU Compliance with BSI's Richard Holborow and RQM+'s Amie Smirthwaite Join us for what will surely be a captivating and informative conversation aiming to help you master EU compliance, where BSI's Global Head Clinical Compliance Richard Holborow and RQM+'s Senior Vice President of Intelligence and Innovation Amie Smirthwaite come together to address current challenges and provide valuable insights on navigating the complex landscape of EU regulations. This conversation will: Empower manufacturers Alleviate fears Equip manufacturers with practical guidance to succeed in the European market Richard and Amie at a glance... Richard: Unparalleled insider knowledge from renowned notified body BSI, sharing exclusive industry insights Amie: Seasoned regulatory professional and former notified body leader, with extensive manufacturer feedback and practical experience Key Topics of Discussion Notified body capacity: Current status and future outlook, with insights into the impact of regulation 2022-14 and collaborative efforts among notified bodies Overcoming challenges: Strategies for both legacy and new devices, ensuring successful market access and maintaining a robust product pipeline in Europe Streamlining the certification journey: Easy fixes manufacturers can implement to improve submissions, enhance the certification process, and simplify their path to compliance Certificates with conditions: Latest developments, common challenges, and guidance on effective approaches And more! Additional insights and topics to provide a comprehensive understanding of EU regulations, including answering your questions! Benefits for Attendees Gain exclusive insights and industry knowledge from insiders Demystify EU regulations and alleviate fears Obtain practical guidance to navigate the European market successfully Learn actionable strategies to enhance submissions and streamline the certification process Stay updated on certifications and conditions Don't miss your chance to join Richard and Amie in what we expect to be an enlightening conversation, and one that promises to clarify EU regulations and empower manufacturers to thrive. Register now to secure your spot! More About Richard and Amie Richard Holborow – Head of Clinical Compliance, BSI Prior to his role at BSI, Richard worked as a clinical physiologist for 16 years within the National Health Service (NHS) specializing in implantable cardiac devices and electrophysiology. Richard joined BSI in 2018 bringing his clinical expertise and passion for clinical data to the organization. Richard is also involved with the working groups of the Medical Device Co-ordination Group (MDCG) for the EU. Amie Smirthwaite – Sr. VP of Intelligence & Innovation, RQM+ Dr. Amie Smirthwaite is the Senior Vice President of Intelligence and Innovation at RQM+ and joined the company in March of 2020. A clinical and regulatory affairs expert, Amie has over 25 years of postdoctoral experience in medical devices, spanning new product development, quality and regulatory systems, and clinical data evaluation.   She is leading the RQM+ Intelligence and Innovation team, following her role as former Global Head of Clinical Compliance at BSI. Amie developed BSI’s clinical compliance team and lead clinical aspects of BSI’s successful MDR designation and has contributed to numerous clinical and regulatory guidance documents and training.  #### Is Your E&L Testing Strategy Future-Ready? Checklist Are you stuck using outdated or incomplete extractables and leachables (E&L) strategies? This checklist offers a fast, clear way to pressure-test your current approach across five areas:  Chemistry readiness  Analytical sensitivity  Quantification  Supplier controls  Timeline predictability  Use it to uncover gaps that lead to costly delays — and see how RQM+ and Jordi Labs deliver faster timelines, smarter science, and unmatched integration with regulatory and clinical strategy.  #### IVDR Class D Devices: Advanced Strategies for Succeeding In a Dynamic Regulatory Environment Certification of Class D devices present additional challenges for manufacturer's due to the additional requirements for these high-risk devices. The challenges are further complicated because the infrastructure required in the IVDR is not fully in place. While notified bodies are moving forward with certification of these devices, the path forward and current state of play can be confusing. The targets seem to be constantly changing, making it difficult to prepare for certification of these devices. In this Live! show we discuss: Current status on EURLs and draft common specifications What steps notified bodies are taking in lieu of EURLs What can you do to be prepared for your technical review And much more, including answering your questions! Sign up to watch the Live! show on demand. Panelists: Margot Borgel – Director, IVD Intelligence & Innovation Bethany Chung, Ph.D., RAC – Principal Regulatory Scientist Lindsay Wright – Senior Consultant / Capability Manager Nancy Morrison, RAC – Vice President, Intelligence & Innovation (moderator) #### Jordi Labs’ Lumo: Accurate Response Factors that Strengthen TRA and E&L Decisions ⏺️ Recorded December 11, 2025 Panel overview Response-factor variation is a core barrier to reliable quantitation in extractables and leachables (E&L). This expert session focuses on why response-factor accuracy matters downstream and how Lumo’s predictive response factors make toxicological risk assessment (TRA) and regulatory dialogue more defensible, and when targeted experiments are still needed. We’ll keep the spotlight on decision quality, uncertainty handling, and practical boundaries for semi-quantitative work. What you’ll learn TRA impact: how tighter response-factor accuracy shifts margins of safety and escalation decisions. Defensibility for regulators: documenting assumptions, uncertainty, and flags in the ISO 10993-18 context. When predictions are enough: a clear rubric for moving from predictive results to targeted standards. Real-world scenarios: representative compound classes (e.g., phenols, esters, acids, sulfur species) and what changes with better RFs. Operational handoff: the deliverables RA/TRA reviewers need with semi-quantitative results. Who should attend E&L scientists, RA/QA leaders, and toxicologists seeking decision-ready semi-quantitative data that stands up in submissions. Panelists  Ron Brown – Toxicologist, Risk Science Consortium Ted Heise – Senior Regulatory Scientist, MED Institute Kevin Rowland – Executive Vice President and General Manager of Lab Services, Jordi Labs, an RQM+ company Yuanlin Deng – Senior Chemist II, Jordi Labs, an RQM+ company Certificate of attendance available upon request for live attendees. #### Lumo™: AI-Powered Response Factor Prediction for E&L Move Faster With Defensible, In-Silico Results  In extractables and leachables (E&L) testing, response factor variability creates uncertainty, especially when no reference standard exists or the chemistry is unfamiliar. Lumo™ uses neural network modeling to predict response factors in silico, so you can accelerate quantitation without chasing calibrations.  What Lumo™ Does: Lumo™ predicts LC-MS and GC-MS response factors from molecular descriptors using chemistry class-specific sub-models. Built-in checks flag low-confidence predictions for expert review, so you know when to trust the output and when to verify.  Why It Matters:  Speed: Predicted response factors shorten turnaround and free lab capacity  Focus: Low-confidence cases are flagged automatically for targeted follow-up  Confidence: Predictions meet acceptance criteria for semi-quantitative work  Efficiency: Fewer reference standards needed and less instrument time consumed  Where Lumo™ Fits in Your Workflow: Use Lumo™ during non-targeted screening and semi-quantitative phases to manage unknowns, plan follow-up testing, and support toxicology assessments. Reserve full calibrations for the compounds that truly need them — an approach aligned with risk-based strategies in ISO 10993-18.1  Reference 1 International Organization for Standardization. (2020). ISO 10993-18:2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process. https://www.iso.org/standard/64750.html  #### Material Matters: Navigating Risks and Strategies for Improving Medical Device Safety We all know: ensuring the safety and efficacy of medical devices is critical to protecting patients and minimizing risks to healthcare providers. One of the key challenges in achieving this goal is selecting and managing materials effectively, while maintaining supplier controls and identifying opportunities for proactive design changes. In this panel discussion, experts in medical device development, regulatory compliance, and material science will share their insights on navigating material risks and implementing strategies to improve medical device safety. Topics will include: Best practices for material selection and supplier controls in medical device development Strategies for proactive risk management, including early identification and mitigation of material-related risks Approaches to biocompatibility testing and regulatory compliance in medical device development The changing landscape of medical device regulation and its impact on material selection and supplier controls Case studies and practical examples of effective material risk management in medical device development Attendees will come away from this session with a better understanding of how to navigate material risks in medical device development and implement effective strategies for improving safety and quality. Panelists Jaishankar (Jai) Kutty, Ph.D. – Vice President, Intelligence & Innovation, RQM+ Kevin Rowland – Director of R&D, RQM+ Taryn Meade – Director of Biological Evaluation Consulting, RQM+ Christine Santagate – Chief of Staff, Lab Services (moderator) #### MDCG 2023-7: New Clinical Evidence Pathways for Legacy and New Devices MDCG 2023-7 was published in December 2023, providing much needed clarification on the use of equivalence for implantable and Class III devices, and when these devices can be exempted from mandatory clinical investigations. The guidance corrects a long-standing misperception previously held by many in MedTech, namely, that equivalence cannot be claimed with another manufacturer’s device without a contract allowing full access to the technical documentation on an ongoing basis. This in turn provides new opportunities to expand clinical evidence packages, helping to maintain devices and indications in the EU market, as well as potentially supporting new product development. This session will explain the background to this guidance and how it clarifies the legal text of the MDR, and how it can be used to support clinical evidence requirements for devices still in the process of transition from the Directives to EU MDR, as well as how it can be used to support new product development. It will also discuss how “sufficient access” to the data required to justify equivalence claims can be demonstrated. After attending the panel discussion, you will be able to: Ensure they have the strongest possible clinical data packages available for their devices, giving their devices the best chance of staying on / entering the EU market with the full set of indications Provide a strong rationale for “sufficient access” to the data required to establish equivalence, reducing potential notified body findings RSVP by completing the form and we'll email connection details. We'll be sharing exclusive content with those who RSVP as well! Panelists:  Amie Smirthwaite BEng, Ph.D., FRAPS, – Senior Vice President, Scientific Affairs Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs Jon Gimbel, Ph.D. – Vice President, Technical Consulting Services Bethany Chung, Ph.D., RAC – Senior Principal Regulatory Scientist BONUS: If you want to get the most out of the session, be sure to watch this summary video from Jai beforehand. This video covers the basics of why this is an important topic and we'll answer your questions during the discussion. #### MDR and IVDR Amendments:Strategies for Supply Interruption Compliance Featuring guests from TÜV SÜD and Axon Science Based Lawyers Live! #82 presentation and panel  |  Recorded 12 September 2024 Available on demand. The recently published Regulation (EU) 2024/1860 amends the EU Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) by introducing some significant changes that will impact manufacturers and the entire MedTech industry. One of the changes is the introduction of a requirement for manufacturers to inform national competent authorities in cases of supply chain interruptions, or the withdrawal from the market, of certain critical medical devices and IVDs. Join our expert panel to explore the implications of these new obligations for manufacturers and learn actionable strategies to ensure compliance. In this comprehensive discussion, our regulatory and quality experts will cover: Impact Assessment: An overview of the amendments, including changes to transition timelines for IVDR and the phased rollout of EUDAMED. Supply Chain Management: Insights into the new obligation for manufacturers to provide advanced notice of supply chain interruptions and strategies to ensure a robust and resilient supply chain. Industry Perspectives: An examination of feedback from industry stakeholders and how companies are preparing for these regulatory changes. Compliance Strategies: Guidance on meeting the new requirements, including implementation within your Quality Management System (QMS). Quality and Regulatory Support: How RQM+ can support your company with regulatory change assessments, EUDAMED data management, and the implementation of new supply chain notification processes. Who Should Attend: This panel discussion is ideal for regulatory affairs professionals, operations management, quality assurance professionals, production planning and supply chain managers, and MedTech manufacturers navigating the amended IVDR and MDR requirements. By attending this event, you will gain a clear understanding of the amendments to MDR and IVDR and learn practical steps and strategies to achieve compliance. Register now to stay ahead of these critical regulatory changes and ensure the continued success of your products in the European market. Complete the form on this page to watch the recording and download the slides. Panelists and moderator: Erik Vollebregt – Advocaat, Axon Science Based Lawyers Heike Moehlig-Zuttermeister – Global Director In-Vitro Diagnostics, TÜV SÜD Donielle Johnson – Global Regulatory Affairs Executive Ed Ball – Manager, Intelligence & Strategic Execution, RQM+ Amie Smirthwaite, Ph.D. – Senior Vice President, Scientific Affairs, RQM+ (moderator) Certificate of Participation available upon request for live attendees. #### Modernizing MedTech Research via Hybrid Study Approaches to Enhance Your Patient Recruitment RQM+ Clinical Trials Chief Operating Officer, David Novotny, joined THREAD CEO John Reites in May 2024 to discuss MedTech study examples that utilize hybrid study approaches to accelerate patient recruitment. David and John explore specific study designs that lend themselves to hybrid approaches, such as pre- and post-market clinical studies and randomized controlled trials. They emphasize the importance of listening to patient feedback and incorporating human-centered design thinking to create more flexible and patient-centric study protocols. They also discuss the impact of hybrid approaches on recruitment, including expanded recruitment areas and increased patient engagement. Compliance considerations and strategies for working with less tech-savvy populations are also addressed. To hear this conversation on demand, please complete the form on this page. Sections 00:00 Introduction and Overview03:16 Types of Study Designs for Hybrid Approaches09:07 Examples of Hybrid Approaches in Med Tech Studies16:05 Impact of Hybrid Approaches on Patient Recruitment28:26 Strategies for Working with Older Populations in Hybrid Studies #### Neural Network Response Factor Prediction for E&L The Peer-Reviewed Science Behind Lumo™  Accurate quantitation in extractables and leachables (E&L) analysis is complicated by response factor variability, especially in mass spectrometry-based screening methods. This peer-reviewed paper, published in the PDA Journal of Pharmaceutical Science and Technology, introduces in-silico prediction models that help address this challenge.1  What the Paper Covers:  The problem: Variability in LC-MS and GC-MS response factors introduces uncertainty into semi-quantitative E&L workflows  The approach: Neural network models trained on diverse chemical descriptors, organized into chemistry class-specific sub-models  The outcome: High-quality response factor predictions that reduce the need for empirical standards while maintaining defensible accuracy for screening-phase quantitation  Why It Matters: This research forms the scientific foundation for Lumo™, Jordi Labs’ AI-powered response factor prediction capability. The methodology enables faster E&L turnaround, reduced calibration workload, and clearer paths to toxicological risk assessment without sacrificing rigor.  Reference 1 Deng, Y., Grice, A., Louis, M., et al. (2026). Neural Network Prediction of Response Factors for Extractables and Leachables in Pharmaceuticals and Medical Devices. PDA Journal of Pharmaceutical Science and Technology. https://journal.pda.org/content/early/2026/01/30/pdajpst.2025-000061.1 #### Neurons on Fire: The MedTech Revolution You Can't Afford to Miss Executive takeaways for MedTech decision-makers An evidence-aware briefing on seven forces reshaping neurology MedTech, with case examples, regulatory / reimbursement takeaways, and practical next steps for product and program leaders. You’ll learn: The seven catalysts: AI/ML, advanced imaging, robotics/minimally invasive, digital health/telemedicine, precision medicine, neurostimulation, and BCIs. You'll get a feel for what they enable today and where they’re headed. How to act: Each section gives critical insights, brief case examples, lessons learned, regulatory & reimbursement implications, and RQM+ recommendations you can apply on your own or with help from RQM+. Context that informs decisions: An executive overview with key milestones to frame timing and risk. Backed by citations: 30 full references to support claims and examples. Who should read: MedTech manufacturers and innovators across neuro, neurovascular, neuro-oncology, digital/AI, and BCI. Leaders in Regulatory Affairs, Quality, Clinical/Medical Affairs, R&D, Product/Program Management, Market Access/Reimbursement, and Corporate Strategy—anyone steering pipeline, submissions, or go-to-market. Outcome: A shared, cross-functional playbook to align teams, de-risk development, and focus investments where the evidence and adoption signals are strongest. Download the paper now by completing the form on this page. About the Author Jaishankar Kutty, PhDVice President, Regulatory, Reimbursement, & Market Access With over 16 years of distinguished experience in the medical device industry, Jai brings robust expertise in R&D, clinical, and regulatory leadership from roles at BSI and St. Jude Medical to his position at RQM+. At RQM+, he leveraged EU-notified-body expertise to guide manufacturers through complex clinical and regulatory landscapes, specializing in clinical/regulatory strategy, clinical study design, retrospective data gathering, biological safety evaluations, interaction with regulatory agencies, and benefit-risk analyses. Jai ensures rigorous compliance and drives advancements in evidentiary foundations for legacy devices. At BSI, he spearheaded CE marking for cutting-edge cardiovascular technologies and played a critical role in securing MDD re-designation for the UK and achieving MDD/MDR designations for Dutch notified bodies. Jai contributed to groundbreaking advancements in surgical and transcatheter heart valve technologies, including innovations in septal closure, vascular closure, and renal denervation, setting new benchmarks for R&D and clinical excellence.​ #### October Overview: Essential Insights from an Eventful Month in MedTech Watch our RQM+ Live! show from October as Boston Scientific's Sr. Global Regulatory Intelligence & Advocacy Manager joined RQM+ experts for a special edition of our Live! show, all about the month's industry events! This session brings together insights from an array of events our team attended throughout October, such as the RAPS Convergence and The MedTech Conference (AdvaMed). We've soaked in knowledge, experiences, and taken note of industry updates. Now, we're excited to come together and share the crux of what we've discovered — the revelations, shifts, and noteworthy advancements. We'll touch upon: Key topics from a broad spectrum of events Crucial shifts in industry practices and guidelines Overarching themes that resonated across various conferences Answering questions and providing clarity on intricate topics Whether you attended any of the October events or not, this session is a golden opportunity to gain a consolidated perspective of the busiest month in MedTech and draw connections between different events. Want to watch? Fill out the form to watch on demand! Panelists: Olga van Grol-Lawlor – Sr. Global Regulatory Intelligence & Advocacy Manager, Boston Scientific Amie Smirthwaite, Ph.D. – Sr. VP of Intelligence & Innovation, RQM+ Nancy Morrison, RAC – Vice President, Intelligence & Innovation, RQM+ Dirk Steenmans – Global Head, Clinical and Post-Market Practice, RQM+ Theresa Miles – VP, Client Portfolio Management, RQM+ (moderator) #### PART 1: Medical Device Cybersecurity: Proven Strategies for Connected Devices and SaMD As software and connectivity reshape MedTech, implementing effective cybersecurity measures has become business-critical. Join our expert panel for a practical, strategic discussion that cuts through the complexity of cybersecurity guidance and delivers actionable insights for medical device manufacturers. Our panel of industry experts will provide clear, implementable guidance on: Practical strategies for meeting EU MDR and US FDA cybersecurity requirements - with real-world examples and documentation approaches Essential security considerations for medical devices, IVDs and SaMD development How to integrate cybersecurity requirements into your quality management system from the start Standards for risk management, pre- and post-market considerations that satisfy both regulatory requirements and long-term security objectives Strategic planning for maintaining security throughout your product lifecycle Common pitfalls to avoid in cybersecurity implementation and regulatory submissions The role of SBOMs (Software Bills of Materials) in achieving transparency and regulatory compliance Panelists: Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovation, RQM+ Mirko Raner – Cybersecurity Consultant, RQM+ Hrishikesh Gadagkar – Senior Principal, RQM+ Moderator: Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+ Register now to gain practical insights that will help you navigate the evolving cybersecurity landscape with confidence, backed by RQM+'s extensive experience in medical device regulatory compliance and software validation. Certificate of Participation available upon request for live attendees. #### PART 2: Medical Device Cybersecurity: Proven Strategies for Connected Devices and SaMD As software and connectivity reshape MedTech, implementing effective cybersecurity measures has become business-critical. Join part two of our expert panel for a practical, strategic discussion that cuts through the complexity of cybersecurity guidance and delivers actionable insights for medical device manufacturers. Our panel of industry experts will provide clear, implementable guidance on: Practical strategies for meeting EU MDR and US FDA cybersecurity requirements - with real-world examples and documentation approaches Essential security considerations for medical devices, IVDs and SaMD development How to integrate cybersecurity requirements into your quality management system from the start Standards for risk management, pre- and post-market considerations that satisfy both regulatory requirements and long-term security objectives Strategic planning for maintaining security throughout your product lifecycle Common pitfalls to avoid in cybersecurity implementation and regulatory submissions The role of SBOMs (Software Bills of Materials) in achieving transparency and regulatory compliance Who Should Attend: This session is essential for medical device manufacturers, software developers, quality professionals, and regulatory teams working with connected devices or SaMD. Whether you're bringing your first connected device to market or optimizing your current cybersecurity approach, you'll gain practical insights for ensuring both compliance and security. Panelists: Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovation, RQM+ Mirko Raner – Cybersecurity Consultant, RQM+ Hrishikesh Gadagkar – Senior Principal, RQM+ Moderator: Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+ Register now to gain practical insights that will help you navigate the evolving cybersecurity landscape with confidence, backed by RQM+'s extensive experience in medical device regulatory compliance and software validation. Certificate of Participation available upon request for live attendees. #### PMCF Surveys That Survive Scrutiny ⏺️ Recorded October 2, 2025 PMCF surveys can strengthen your CER and PSUR or create rework. In this 60-minute panel with live audience Q&A, RQM+ leaders from regulatory, clinical, and scientific writing share what MDR reviewers look for and how to design surveys that generate decision-grade evidence. The session is intended for regulatory affairs, post-market surveillance, clinical evidence, and medical writing leaders at MedTech manufacturers.  Join to learn how to:  Define clear objectives, endpoints, and target population so the survey maps to your PMCF plan and CER.  Improve response rates without bias and capture higher-quality data, including adverse events and usability feedback.  Learn how to position your physician level survey as a chart review.  Document methods, rationales, and traceability so notified bodies can follow the logic.  Avoid the top reasons reviewers push back on PMCF surveys and how to correct them.  Walk away with a practical checklist to pressure test your next PMCF survey and reduce review risk.  Who should attend:  Regulatory affairs leaders and PMS managers.  Clinical evidence and clinical operations leads.  Scientific and medical writing leaders, including CER and PSUR authors.  Quality leaders responsible for post market surveillance programs.  Panelists and moderator:  Torrie DeGennaro – Vice President, Scientific & Medical Writing  Bethany Chung, Ph.D., RAC – Director, Technical Solutions & Innovation  Garrett Jeffries, Ph.D. – Principal  Jon Gimbel, Ph.D. – Vice President, Regulatory Affairs  Certificate of attendance available upon request for live attendees. #### Practical Points in Creating Clinical Evidence for AI SaMD Medical Devices Download the slides and watch the recording This webinar was initially presented in March 2023 at CSMD2023. Artificial intelligence (AI)- and machine learning (ML)-based medical devices, once a dream of science fiction writers, have firmly established their place in the market and will continue to gain in popularity in the coming months and years. With uses ranging from virtual assistance to image analytics to robotic-assisted surgeries, manufacturers have only begun to explore the utility and value of these devices. Such rapid innovation, however, can cause severe regulatory headaches. The relatively controlled and documented methods applied to R&D of conventional medical devices are not traditionally practiced in the highly agile environment of AI/ML algorithm development. This presentation will highlight standards that can be followed to bring an added layer of rigor to the development and documentation of AI/ML-based medical devices. In addition, it will cover Good Machine Learning Practices that will aid manufacturers in designing proper validation and clinical testing procedures to enable a smoother regulatory submission process. Meet The Presenter: Bethany Chung, Ph.D., RACPrincipal Regulatory Scientist Bethany has a Ph.D. in biomedical engineering and loves all things quantitative. She has more than 10 years of experience with medical devices in the clinical space. Prior to joining the regulatory world, she was a clinical researcher specializing in ML and AI-based devices, and she is currently in the Clinical and Post Market Practice at RQM+. #### Pragmatic and Compliant Approaches to Clinical Evidence What type of evidence is considered sufficient to comply with the MDR? While we've spoken about this extensively in the past, we explore more ways to arrive at the answer and address many more questions in this RQM+ Live! show recorded 27 April! We were asked for this topic and we have plenty we're excited to share.Perhaps in certain situations you're asking yourself, "What kind of clinical evidence do I need for my device?" Our seasoned panelists shared ways to determine exactly that by sharing recent thought processes and examples. We set the tone upfront with a list of factors that affect the 'definition' of sufficient clinical data, generally speaking: intended purpose, novelty, benefit-risk profiles, number of indications, users, where it's used in the world and supportive non-clinical data... just to name a few. More specifics on what this session covered: Less burdensome, yet effective ways to comply with clinical requirements, using examples from a variety of device types How do you collect clinical data for standard of care devices? How and when can you use Article 61(10) and what is an indirect benefit? Does it make sense for software devices? Is equivalence really no longer useable for Class III and implantable devices? Why monitoring the SOTA could potentially save your company from wasting resources and is much more than just another regulatory requirement Evidence for Annex XVI products (products with no intended medical purpose) This was a loaded session that our team was incredibly excited about! We tried to provide as much actionable value as possible. Panelists: Amie Smirthwaite, BEng, Ph.D. – Senior Vice President, Intelligence & Innovation Jon Gimbel, Ph.D. – Vice President, Technical Bethany Chung, Ph.D., RAC – Principal Sally Sennitt – Medical Director, Intelligence and Innovation #### Pre-Submission to Preeminence: Showcasing FDA's Latest Pre-Sub Guidance and Uncovering PCCP Best Practices This panel discussion was all about the FDA's latest pre-submission guidance, with an emphasis on best practices for Predetermined Change Control Plans (PCCP). As always, we took questions from the audience and answered as many as we could!  Key points of discussion included:  Unveiling FDA's new pre-submission guidance and its implications  Pros and cons of implementing pre-submission meetings for regulatory success Leveraging pre-submission meetings for QSR follow-ups and risk mitigation A thorough exploration of PCCP (beyond just software); some specifics include: Applicable to PMA and 510(k) devices (previously not available for 510k devices unless the predicate had one) Includes labeling for the proposed change and performance requirements for changes made under the plan Allows manufacturers to make pre-planned changes without a new submission If choosing a predicate, it must be what was reviewed by FDA and not the device version that underwent a change control plan Understanding the 2022 Omnibus Appropriations Bill: Streamlining PCCP submissions How RQM+ empowers clients with comprehensive support in this area, from package preparation to remediation  Don't miss this opportunity to explore the advantages, potential challenges, and optimal approaches to leverage pre-submission meetings and PCCPs. We hope you’ll join our experienced and versatile team as they explore these topics and answer your questions.   Complete the form to watch on demand!  Panelists: Nancy Morrison, RAC – Vice President, Intelligence & Innovation Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovation Hrishikesh Gadagkar – Principal Engineer Bryan Pinder, RAC – Principal Engineer (former FDA CDRH Lead Reviewer) #### Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation The Future of Inclusive Healthcare Innovation Healthcare equity is a goal we can achieve—by transforming how we conduct clinical trials. This white paper, "Shattering Barriers: Advancing Healthcare Equity by Enhancing Diversity in Clinical Trials for a Future of Inclusive Innovation," authored by Jaishankar Kutty, Ph.D., presents a realistic roadmap for increasing diversity in clinical trials. It provides actionable insights towards strategies and tactics based on FDA perspective and industry best practices that pave the way for more inclusive and equitable healthcare innovations. Why Read This White Paper?  Medical devices and in vitro diagnostics (IVDs) must be safe and effective for everyone, regardless of demographic or socioeconomic background. Yet, for too long, clinical trials have fallen short in representing the diversity of the populations they aim to serve. This paper delves into the crucial need to improve diversity in clinical trials, aligning with FDA guidance and industry best practices to ensure that all individuals benefit from the latest medical advancements. What you'll Learn FDA's Perspective & Global Alignment: Understand the regulatory framework and the FDA's commitment to advancing healthcare equity through improved diversity in clinical trials.  Learn how aligning with international regulatory standards can enhance trial outcomes and position your products for global success. RQM+ Strategies and Operational Recommendations: Discover practical, actionable strategies from RQM+ experts for overcoming the challenges of implementing diverse clinical trials. Get insights into the practicalities of recruiting diverse populations, managing complex data, and utilizing adaptive trial designs to meet inclusivity goals without compromising trial integrity. Who should read this? This white paper is essential for medical device manufacturers, clinical researchers, regulatory professionals, and healthcare leaders committed to advancing healthcare equity through innovation. Whether you're navigating the complexities of FDA regulations or looking to enhance global trial outcomes, this comprehensive guide offers the expertise and strategies you need to succeed. Meet the author Dr. Jaishankar Kutty, a visionary in the medical device industry, brings over two decades of transformative leadership in clinical and regulatory affairs. As Vice President of Global Regulatory Affairs at RQM+, he spearheads strategies that guide global manufacturers through complex regulatory landscapes, ensuring both compliance and innovation. Dr. Kutty's distinguished career includes pivotal roles at BSI, where he led CE marking efforts for groundbreaking cardiovascular technologies, and at St. Jude Medical, where his work in surgical and transcatheter heart valve technologies, renal denervation, and percutaneous closure technologies set new industry standards.  A thought leader in clinical research, Dr. Kutty has made significant contributions to the development of clinical strategies that drive successful trial outcomes.   In this white paper, Dr. Kutty brings his deep expertise in clinical strategy and study design to bear on the critical issue of increasing diversity in clinical trials. His insights are essential for anyone seeking to enhance trial outcomes while promoting healthcare equity and innovation. For more on clinical trials - Beyond Inclusion: Reimagining Equity and Real-World Impact in Heart Failure Trials #### Start 2023 Right: Smart and Savvy Tips from Former Regulators and Notified Bodies On Thursday, 26 January 2023, RQM+ subject matter experts hosted episode #63 of our Live! show. Fill out the form to get access to the on-demand recording now. The MedTech industry is one of the most heavily regulated industries in the world. The regulatory landscape is changing rapidly and regulations are increasingly more complex.An efficient and scalable regulatory strategy is now more important than ever. As regulatory bodies worldwide update and enforce regulations at an accelerated pace, the need for speed and flexibility in regulatory functions has never been more critical. The alternatives are failed and damaging regulatory submissions that could ultimately stop a product from coming to market.In this RQM Live! show, our panelists will bring their unique perspectives on the world's largest regulatory markets, the US FDA and EU MDR/IVDR. Our subject matter experts will: Discuss the greatest challenges in regulatory submissions to the FDA and notified bodies Provide advice on how to overcome these challenges Identify synergies and differences between EU and US regulators Provide top tips for successful product submissions and interaction with EU/US regulators Please join us! We hope our advice will help you throughout your year. Panelists: Amie Smirthwaite, BEng, Ph.D. – Senior Vice President, Intelligence & Innovation Jaishankar (Jai) Kutty, Ph.D. – Vice President, Intelligence & Innovation Carlos Galamba, MSc – Vice President, Intelligence & Innovation - IVD Allison Komiyama, Ph.D., RAC – Vice President, MedTech Innovation Jon Gimbel, Ph.D. - Vice President, Technical #### Structured Dialogue: How to Engage with Notified Bodies Featuring guests from BSI, TÜV SÜD, and GMED Live! #83 presentation and panel  |  Recorded 4 October 2024 Available on demand. Join us for an exclusive panel discussion featuring top experts from TÜV SÜD, GMED, and BSI as they dive into the intricacies of structured dialogue between MedTech manufacturers and notified bodies. As regulatory expectations continue to evolve under MDR and IVDR, these dialogues are vital for ensuring compliance and expediting market access.  Our panelists will provide valuable insights into key topics such as:  Effective strategies for engaging with notified bodies in structured dialogues Managing device classifications, submission processes, and project timelines How to navigate changes in notified bodies and maintain compliance Best practices for developing regulatory plans in new technology areas  This session is ideal for regulatory professionals, quality assurance teams, and MedTech manufacturers seeking practical guidance on optimizing their interactions with notified bodies.  Don't miss this opportunity to learn from leading voices in the industry and gain actionable strategies to ensure regulatory success. This session will be invaluable for anyone navigating MDR/IVDR compliance. Register today to secure your spot!  Panelists:  Alex Laan – Head of the IVD Notified Body, BSI Dr. Andreas Stange – Senior Vice President MHS Regulatory & Quality, TÜV SÜD Tom Patten – IVDR/IVD International Manager, GMED  Moderator:  Jaishankar (Jai) Kutty, Ph.D. – Vice President, Global Regulatory Affairs, RQM+  Certificate of Participation available upon request for live attendees. #### The Business Case for Outsourcing Medical Device Product Life Cycle Management  A MedTech Operational Efficiency Report What’s the real cost of fragmentation in MedTech? This report breaks down how relying on siloed vendors or overloaded internal teams leads to missed milestones, repeat testing, and millions in lost revenue.   Inside, you’ll get real-world examples of submission recovery, M&A integration, and global launch acceleration powered by RQM+’s SMART Solutions framework — a model proven to reduce drag, boost predictability, and protect valuation.  You’ll Learn:  Where most MedTech operational drag originates and how to fix it  Why delays in submission cost more than time  How integrated outsourcing enables parallel FDA + EU launches  The cost of missed reimbursement strategy   How SMART Solutions replace tactical outsourcing with unified governance  Who Should Read:  MedTech executives and investors evaluating outsourcing ROI  Regulatory, clinical, and quality leaders seeking scalability  Program managers navigating EU MDR/IVDR, FDA, or global reimbursement  Download the report now to see how treating regulatory, clinical, lab, and reimbursement as one integrated system drives efficiency and submission speed.  #### The Evolving Biocompatibility Landscape: Staying Ahead of Regulatory Requirements On Thursday, 16 February 2023, RQM+ subject matter experts hosted episode #64 of our Live! show. Fill out the form to get access to the on-demand recording now. Over the past several years the expectations for testing of medical devices per the ISO 10993 standards has significantly changed and continues to change at a rapid pace. Furthermore, different regulatory bodies have different expectations when evaluating this data. Failure to understand these expectations and an inappropriate choice of testing labs can result in product delays and repeat testing. The expert panel will: Describe how chemical characterization, toxicological risk assessment and biological testing work together to evaluate a device Explain how to ensure method sensitivity, maximize quantitative accuracy and identification confidence Highlight which validation experiments are expected for chemical characterization Discuss the major points of departure between European notified bodies and US FDA Explain which certifications are necessary for laboratories Show how controls used, and when are they necessary in biological testing Evaluate how revisions to ISO 10993-17 may impact toxicological risk assessment Panelists: Joel M. Cohen, Sc.D., DABT – Principal, Gradient   Jaishankar (Jai) Kutty, Ph.D. – Vice President, Intelligence & Innovation, RQM+ Kevin Rowland – Director of R&D, RQM+ Taryn Meade – Director of Biological Evaluation Consulting, RQM+ Nancy Morrison, RAC – Vice President, Intelligence & Innovation, RQM+ (moderator) Please sign up to access the recording by filling out the form.  #### The German DiGA Idea: Revolutionizing Healthcare with Digital Health Applications Unlocking the Potential of DiGA for Global Health Care Improvement  Explore how the DiGA concept, originally pioneered in Germany, is revolutionizing health care by making validated health technologies accessible and reimbursable for patients. This white paper delves into the success of patient-centered digital innovations that are rigorously tested to ensure they deliver the claimed health care benefits. Discover how this transformative concept is rapidly gaining traction across Europe and catching the attention of the US health care landscape.  Why Read This White Paper?  Stay ahead of the curve with in-depth analysis and practical examples of how DiGA is shaping the future of digital health care. Whether you're a health care provider, researcher, or industry professional, this white paper offers valuable insights into the optimization of health care provision in a digitizing world. Learn about the challenges, constraints, and the immense value DiGA brings to the table.  DOWNLOAD YOUR COPY NOW Don't miss out on this essential resource for understanding the evolving landscape of digital health care. Download our white paper today and discover how you can leverage DiGA to enhance health care outcomes and drive innovation in your organization.  #### The Investigative Science of Smart Cardiac Implants: Securing Compliance Through Complex Chemical Characterization The proliferation of “smart” cardiac implants — featuring integrated sensors, miniaturized power sources, and active communication — has brought significant change to the MedTech regulatory landscape. While traditional stents and valves primarily required mechanical durability, today’s connected implants introduce a potentially volatile cocktail of polymers, adhesives, and electronics.1 These components must remain stable and biocompatible for years while maintaining hermetic integrity in a high-pressure, blood-contact environment.2  For R&D and regulatory leaders, the main hurdle to a successful regulatory submission is managing the chemical characterization of these multi-material stacks.3  Why Smart Devices Outpace Standard Medical Device Testing Services  Standard testing models often fall short when applied to smart devices. In an energy-dependent implant, factors like battery heat, electrical pulses, and continuous sensor activation create a dynamic environment. These active factors can accelerate material degradation and alter leaching kinetics, potentially triggering unforeseen interactions between polymers and metals that simple tests might miss.1  At Jordi Labs, an RQM+ company, we treat medical device testing services as a forensic investigation. We emphasize a robust feasibility step before formal testing begins. This stage is essential for complex devices involving polyurethanes and intricate material stacks, as it identifies potential degradation risks under exaggerated chemical conditions.4 By addressing these risks early, we help our clients prevent the downstream analytical issues that often lead to regulatory delays. Early feasibility testing also reduces timeline risks by revealing material issues before formal studies begin, avoiding costly rework at submission stages.  The Material Complexity Multiplier  Smart implants contain diverse materials, including silicones, fluoropolymers, and hybrid coatings, each with unique stabilizers. When these materials are layered, they don’t just exist in a siloed manner side by side; they interact. The complexity arises from multiple manufacturing steps, supplier variability, and entire material stacks, all of which impact regulatory defensibility.  Interface integrity: Specialized coatings over electronic components can crack due to thermal expansion or residual solvent interaction at the interface  Active leaching: Localized heat from a battery housing can cause plasticizer migration or antioxidant depletion;3,4 this can release compounds that are never detected in standard, room-temperature extractions  Solving the “Unknown Identification” Crisis in High-Risk Implants  The FDA and notified bodies have significantly raised expectations for unknown identification.3,5 In a high-risk cardiac implant, reporting a “total extractables” figure is no longer sufficient for a successful toxicological risk assessment. Regulators expect every detectable peak to be identified to a high degree of scientific certainty to ensure patient safety.5  If a lab report contains numerous “unknowns,” it invites a clinical hold or a major deficiency letter. Our approach emphasizes resolving these peaks through high-resolution mass spectrometry and our proprietary Lumo™ predictive modeling. We use analytical methods that identify unknown chemicals rather than just reporting totals, supporting robust regulatory narratives that link chemical characterization findings to biological risk.  The Power of Lumo™ Predictive Modeling  By utilizing predictive response factors, we reduce the uncertainty that typically complicates the risk assessment process. Rather than applying massive uncertainty factors that can make a safe device look dangerous on paper, we provide more accurate quantification. This allows toxicologists to build a defensible safety case based on real data, ensuring a smoother path through the regulatory submission process.  Strategic Extraction: Sealed Packages and Surgical Precision  A common technical question we address is how to test a sealed electronics package without creating “data noise.” Extracting a full device that contains circuit boards leads to false positives because the process flags materials like copper or lead from internal electronics that will never touch the patient.3  Our material characterization services focus on surgical precision:  Selective extraction: We focus exclusively on patient-contacting materials and justified “indirect” contact points  Scientific rationale: We provide detailed justification to regulators explaining why sealed, non-contacting components were excluded from the study;5 this strategy avoids the “rejection by 1,000 questions” that often stalls a submission  Analytical fingerprinting: We trace any biocompatibility failures back to specific manufacturing aids, cleaning residues, or supplier-specific polymers  Tracing Failures With Material Science Testing  Recalls in the smart cardiac space rarely stem from expected materials. They originate from the “unexpected” — degradation products or impurities hidden within the supply chain. Emerging materials like conductive or thermosensitive polymers often lack historical toxicological benchmarks, making their characterization even more vital.3 These novel materials often behave differently under energy-dependent pathways, complicating traditional extractable and leachable methods and requiring labs to adapt analytical techniques rather than forcing new materials into outdated frameworks.  When a device fails biocompatibility, our failure analysis team of polymer chemists conducts a root-cause investigation. By using advanced material science testing, we employ chemical fingerprinting to trace a failure to a specific batch of raw material or a subtle change in a supplier’s process. This investigative rigor differentiates a medical device testing laboratory that checks boxes from a partner that solves problems and ensures your device reaches the market.  Conclusion: Building for Performance, Not Just Compliance  The most underestimated risk in MedTech is the long-term interaction of multiple materials in energy-dependent implants, such as pulse generators.1 The combination of polymers, metals, coatings, and electronics creates complex aging pathways that can alter device safety and function over time.3 By integrating these considerations into your early feasibility steps, you identify risks before they become submission-ending failures.  As MedTech services continue to evolve toward smarter, more complex devices, your choice of lab partner determines your speed to market. RQM+ and Jordi Labs provide the investigative science needed to turn chemical characterization complexity into regulatory clarity.  References  1 Crawford, M. (2025). What’s Next for Smart Implants in Health Care? Journal of Medical Internet Research, 27, e87975. https://doi.org/10.2196/87975 2 European Commission. (2017). Regulation (EU) 2017/745 of the European Parliament and of the Council on medical devices. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32017R07453 International Organization for Standardization. (2020). ISO 10993-18:2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process. https://www.iso.org/standard/64750.html 4 Association for the Advancement of Medical Instrumentation. (2021). AAMI TIR58:2014/(R)2021, Chemical characterization of medical device materials - Guidance for ISO 10993-18. https://www.aami.org/standards 5 U.S. Food and Drug Administration. (2023). Use of International Standard ISO 10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and #### The MedTech Life Cycle Management Outsourcing Tool Kit Built for MedTech Organizations Rethinking What Their Internal Teams Should Own Most MedTech organizations compare the cost of an outsourced resource to an FTE and conclude that building internally is more cost-effective. But that comparison does not account for idle capacity, ramp time, management overhead, or the revenueimpact of delayed submissions when a team that’s running leanhits a surge event. For functions that are A) operationally essential but not strategic differentiators, B) subject to variable demand, and C) require expertise that is difficult to maintain at full internal capacity, the math consistently favors an integrated partner. This tool kit gives MedTech organizations the frameworks to conduct a systematic evaluation and build an outsourcing model that delivers efficiency, speed, and reduced risk across the full product life cycle. What’s Inside Executive brief making the financial and strategic case for outsourcing compliance-critical, nonrevenue-generating work   Actual cost framework comparing what organizations typically count versus what a complete FTE-versus-outsourcing analysis really requires  Outsource-or-own decision matrix for scoring any function across seven variables   Life cycle outsourcing map showing where external partners add the most leverage   Warning signs self-assessment for regulatory and quality leaders   Partner evaluation checklist distinguishing strategic partners from functional vendors   Surge readiness scorecard assessing whether your organization is positioned to respond to audit, remediation, and submission surge events proactively or reactively  Who This Is For VPs and directors of regulatory affairs, quality, clinical operations, and finance at MedTech and IVD organizations evaluating their current outsourcing model or building the business case for a different one.  #### The Predictive E&L Blueprint Infographic A visual breakdown of how predictive extractables and leachables (E&L) testing with AI-powered modeling with Lumo™ eliminates response factor variation to deliver faster, more defensible chemical characterization for medical devices and combination products.  You'll Learn How Lumo™ Helps:  Predict compound-specific response factors using neural networks  Reduce unnecessary calibrations and lower AET-triggered burdens  Accelerate ISO 10993-18 compliant workflows with fewer “unknowns”  Improve submission defensibility and reduce Additional Information (AI) requests  Cut lab timelines from 22 weeks to as little as 4 weeks in select programs  Who Should Read: MedTech manufacturers and combination product developers navigating ISO 10993-18, chemical characterization, or E&L compliance  Regulatory, Quality, and Lab leaders  Preclinical, Product Development, Clinical Affairs, and Program Management teams who are responsible for submission strategy, testing timelines, or toxicology defensibility  The Outcome:   A predictive, lab-to-toxicology blueprint that reduces E&L uncertainty, accelerates chemical characterization, and strengthens submission confidence.  Download the infographic to see how smarter predictions mean faster programs.  #### The Real Cost of Noncompliance: Leveraging IVDR for Long-Term Savings Leveraging IVDR for Long-Term Savings in the MedTech Industry  The inherent complexity of IVDR has left many organizations grappling with implementation issues. Despite these challenges, IVDR compliance can yield substantial long-term cost savings for MedTech companies.  This paper explores what IVDR means for the MedTech industry and provides insights on turning compliance into a strategic advantage. This White Paper Covers:  What IVDR means for your business Real-world case studies exploring how manufacturers overcame common IVDR challenges Lessons for minimizing IVDR costs and accelerating time-to-market The long-term financial rewards of IVDR compliance MEET THE AUTHORS:  MARGOT BORGEL, Ph.D. DIRECTOR, IVD INTELLIGENCE AND INNOVATION Margot Borgel is an IVD expert at RQM+  who helps her clients in many ways, primarily with IVDR implementation and notified body requirements. Prior to RQM+, Margot was a Technical Specialist at BSI, where she performed technical reviews for IVDR, IVDD, and UKCA certification. She's especially passionate about certification of high-risk devices and enjoyed seeing these devices through IVDR certification while at BSI. Before her notified body work, Margot worked for an IVD manufacturer where she held roles in R&D, manufacturing technical support and manufacturing. JONATHAN GIMBEL, Ph.D. VICE PRESIDENT, TECHNICAL Dr. Jonathan Gimbel joined RQM+ in July of 2014. He has a Ph.D. in Mechanical Engineering from the University of Pennsylvania and is a clinical and regulatory affairs expert with over 20 years of experience in medical devices. Jonathan has a wide variety of clinical and regulatory experience as an academic researcher, key member of a medical device startup, and medical device consultant. This has given him extensive knowledge of biomedical research, new product development, quality systems, FDA and EU regulatory affairs, clinical evaluation, and post-market surveillance activities. Jonathan is currently the Vice President, Technical within RQM+’s consulting services. In this role, he is actively involved in overseeing the technical aspects of the regulatory, quality, clinical evaluation, and post-market practices at RQM+. #### The Review-Reducing PMCF Survey Checklist Pressure-Test Your Survey Design Before Notified Bodies Do  Under EU MDR, a PMCF survey is a clinical evidence instrument. Notified bodies routinely reject surveys that fail to qualify as Level 4 evidence, defaulting them to Level 8 “general feedback” status. The results are deficiency letters, costly rework, and delayed market access.  This checklist helps you evaluate whether your PMCF survey is designed to generate scientifically valid clinical evidence that can withstand regulatory scrutiny.  What You’ll Get:  Objectives & strategy: Are your survey endpoints mapped directly to your PMCF Plan and CER? Have you justified why Level 4 evidence is sufficient for your device class?  Scientific validity: Does your survey include documented methodology, sample size rationale, and measures to minimize recall and sampling bias?  Safety & adverse event handling: Is there a compliant pathway for respondents to report AEs, supported by an internal triage SOP?  Documentation & traceability: Does your final report link findings directly to protocol objectives and clinical claims? Does your documentation reference MDCG 2020-6, -7, and -8?1-3  Who Should Download:  Clinical affairs and regulatory leaders managing PMCF obligations  Teams preparing for notified body technical documentation reviews  Quality and RA managers addressing PMCF deficiency findings  Download the PMCF survey checklist to identify gaps before your next submission and move from feedback-grade data to decision-grade evidence.  References 1 Medical Device Coordination Group Document. (2020). MDCG 2020-6: Regulation (EU) 2017/745: Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC. https://health.ec.europa.eu/system/files/2020-09/md_mdcg_2020_6_guidance_sufficient_clinical_evidence_en_0.pdf 2 Medical Device Coordination Group Document. (2020). MDCG 2020-7: Post-market clinical follow-up (PMCF) Plan Template. A guide for manufacturers and notified bodies. https://health.ec.europa.eu/system/files/2020-09/md_mdcg_2020_7_guidance_pmcf_plan_template_en_0.pdf 3 Medical Device Coordination Group. (2020). MDCG 2020-8: Post-market clinical follow-up (PMCF) Evaluation Report Template. A guide for manufacturers and notified bodies.  #### The Ultimate Medical Device Internal Audit Tool Kit  Practical Frameworks to Move Beyond Compliance Theater  Regulators can spot a “check-the-box” audit program almost immediately. If your internal audits never find major issues but external inspections do, or if your CAPA system keeps producing recurrent findings, your quality management system (QMS) is likely carrying hidden risks.  This tool kit provides the actionable templates and frameworks you need to conduct truly investigative medical device internal audits that uncover systemic gaps before they become costly findings.  What You’ll Get:  A supplier qualification checklist that goes beyond ISO 13485 certificates to evaluate actual process maturity1  A 5-step CAPA response framework for closing high-severity findings permanently  An internal audit plan template built on risk-based prioritization, not fixed rotations  A soft skills field guide for uncovering issues that aren’t visible in documentation  Who Should Download:  QA/RA directors and managers responsible for internal audit programs  Quality leaders preparing for FDA, notified body, or ISO 13485 inspections  Teams experiencing audit backlogs, recurrent findings, or post-inspection remediation  Download the medical device internal audit tool kit now to identify systemic failures before a regulatory inspector finds them.  Reference 1 International Organization for Standardization. (2016). ISO 13485:2016 Medical devices — Quality management systems — Requirements for regulatory purposes. https://www.iso.org/standard/59752.html  #### Transforming Your Risk-Based Monitoring Strategy: The Era of AI, Sensors, and Hybrid Trials Risk-Based Monitoring (RBM) Is No Longer a Clinical-Only Function  Under EU MDR and FDA guidance, ongoing real-world performance and safety monitoring is increasingly required even after market release. Risk-based monitoring has become a core component of life cycle management and post-market clinical follow-up, and the infrastructure most teams built for periodic site visits is not designed to manage what modern hybrid and decentralized trials demand.  This executive brief examines how continuous data streams, AI-enabled oversight, and in silico modeling are transforming the RBM landscape and what MedTech clinical leaders need to address now.  What This Brief Covers  How connected devices and remote sensors have inverted the traditional data paradigm¹  Where AI and machine learning add scalable oversight for processing continuous data streams, and where human validation prevents false positives²  How synthetic data modeling, data filtering, and in silico methods help sponsors stress-test monitoring frameworks before deployment³  The regulatory and ethical requirements governing continuous data collection under FDA guidance and EU MDR¹  Four organizational realities every clinical operations team needs to address to modernize RBM   Who This Is For  Clinical affairs leaders, VP-level clinical operations executives, and regulatory strategists responsible for study oversight design and post-market clinical strategy in MedTech.  References   U.S. Food & Drug Administration. (2024). Digital Health Technologies for Remote Data Acquisition in Clinical Investigations.  Applied Clinical Trials. (2025). Modernizing Clinical Oversight: The Shift to Adaptive Monitoring.  Journal of Clinical Innovation. (2025). The Role of In Silico Modeling in Modern Trial Design.  #### Trials That Pay: Designing Clinical Studies to Optimize Reimbursement and Market Access Maximize Reimbursement and Market Access with Smarter Clinical Trial Design Are your clinical trials setting your MedTech innovation up for regulatory approval—but missing the mark on reimbursement?  Regulatory approval is just the beginning. Without payer support, your MedTech innovation remains underutilized and costly. Design trials that demonstrate both value and safety to ensure your market success from the start. A well-designed clinical study does more than satisfy regulatory requirements—it proves the value of your device to payers, accelerating reimbursement and ensuring sustained market access. Without this strategic alignment, manufacturers risk costly delays, increased trial expenses, and lost market opportunities.  In "Trials That Pay: Designing Clinical Studies to Optimize Reimbursement and Market Access," RQM+ experts break down the critical elements of clinical trial design that optimize both approval and reimbursement success. Through real-world case studies,we illustrate:  How study design impacts regulatory and payer acceptance in the U.S. and EU  The difference between superiority and non-inferiority trials—and why it matters  How clinical evidence can drive payer confidence and improve patient access  The pitfalls of trial design misalignment and how to avoid them  The strategic role of post-market surveillance and real-world evidence  Don’t let poor study design become a barrier to reimbursement. Download the white paper today and learn how to optimize clinical trials for commercial success.  #### We Need to Talk About Risk: The Critical Role of Communication in Risk Management Effective risk management for medical devices and IVDs has never been more critical than it is today. As lessons are learned from real-world incidents and events, consequently, regulatory requirements for safety and performance tighten. As the complexity of devices increases, along with the systems in which they operate, manufacturers must navigate a challenging landscape to ensure the safety and effectiveness of their products. But once you move beyond the requirements of ISO 14971:2019, what sets successful risk management apart? One part of the answer lies in effective communication; from hazard identification, via the disclosure of residual risks, to field safety notices. Join us for an eye-opening 30-minute presentation and additional 15 minutes of Q&A, where RQM+ Manager of Intelligence and Strategic Execution, Ed Ball, MSc CEng MIPEM, will explore the vital role of communication throughout the risk management activities conducted over the course of the medical devices lifecycle. Drawing from his extensive experience in the industry, having worked for the UK’s MHRA and several device manufacturers, Ed will share insights and strategies to help you elevate your risk management processes. This session will cover: The importance of communication throughout the risk management process, from design and manufacturing to post-market surveillance Strategies for fostering cross-functional collaboration and ensuring all stakeholders are aligned Techniques for effectively communicating risks and mitigation strategies to regulatory bodies and end-users Real-world examples demonstrating the impact of communication breakdowns and successes in risk management Opportunities to ask your questions and engage with industry peers facing similar challenges Whether you're a quality assurance professional, regulatory affairs specialist part of a product development team, or working within a healthcare institution, this webinar is designed to equip you with the communication tools and best practices to enhance your risk management efforts. By attending, you'll gain actionable insights to help you proactively identify and mitigate risks, improve device safety, and communicate risk-related information with your customers and end-users alike. Who should watch: Quality Assurance Managers and Directors Regulatory Affairs Professionals Product Development Teams Risk Management Specialists Clinical Affairs Professionals Post-Market Surveillance Teams Please complete the form to watch the recording and download the slides. Presenter Ed Ball, CEng, MIPEM, MIMMMManager, Intelligence & Strategic Execution Ed Ball is Manager, Intelligence & Strategic Execution at RQM+ and formerly worked as a medical device specialist at the UK Medicines and Healthcare products Regulatory Agency (MHRA), and is currently an active member of the UK’s Technical Committees for Medical Device Quality Management and Risk Management standards. He is an accomplished medical device specialist and chartered engineer, who combines a technical understanding of medical devices with regulatory and quality management experience. Ed has 15+ years of practical experience with a wide breadth of medical devices, including but not limited to EU Class I – III, active devices, implantable devices, diagnostic devices, measuring devices, devices used by lay people, and sterile devices.  #### When Regulatory Strategy Becomes a Commercial Advantage By Christine Scheve, Vice President, Client Solutions This spring’s EU MedTech Forum produced a rare kind of consensus. Across panels on diagnostics, software, evidence, and materials, the same theme kept emerging:  The wall that once separated regulatory compliance from commercial success has come down, and the companies adapting fastest treat regulatory strategy like a commercial discipline rather than a downstream checkpoint.  That shift carries more weight in 2026 than it did even a year ago. The EU is midway through a targeted revision of its medical device rules, the European Database on Medical Devices (EUDAMED) IT system is becoming mandatory, AI and software devices are raising the evidence bar, and payers are asking for proof of value earlier in development.   Each pressure point is usually owned by a different team. The advantage belongs to manufacturers who connect them. The forces reshaping EU MedTech in 2026 Christine Scheve, an RQM+ subject matter expert and VP of client solutions, who attended the forum, came back with a clear read of where the pressure is concentrating. Six forces are converging at once, and most of them touch more than one function inside a manufacturer: AI and software as a medical device are scaling fast So are expectations for how that software is validated and monitored after launch MDR and IVDR continue to strain resources The EU is advancing a revision meant to ease administrative burden and certification bottlenecks Commercialization timelines are tightening There is closer scrutiny on execution risk and time to market Evidence generation is expanding into the post-market phase Real-world data and post-market surveillance carry growing weight here EUDAMED is moving from voluntary to mandatory use The first four modules are required starting in May 2026 Materials and contamination risk are under closer review This raises the stakes on biocompatibility evaluation early in design None of these is new on its own. What changed is that they arrived together, and they reward the same kind of behavior: plan across functions early or absorb the cost of fixing gaps later. Regulatory strategy has moved to the front of development For years, regulatory work was something addressed after a design was largely fixed. That sequence no longer fits the market. When reimbursement, clinical evidence, and regulatory planning start at the same time, each one shapes the others in ways that protect the commercialization timeline. Reimbursement is the clearest example. Payers and health technology assessment bodies want evidence of economic value before approval, not after it. A reimbursement strategy built alongside the clinical plan lets a single study serve both regulatory and payer needs, which costs much less than running separate evidence programs one after the other. The same logic drives market access consulting, where coverage decisions depend on data that have to be designed in from the start. Regulatory strategy becomes the connective tissue. It keeps a medical device go-to-market strategy aligned with what each market will actually require, and it turns scattered functional plans into one coherent path from concept to adoption. Materials and evidence risk arise earlier than teams expect Two areas consistently catch programs off guard late in development, and both are easier to manage early: The first is materials risk. Under MDR and IVDR, extractables and leachables work and biocompatibility evaluation carry more weight than ever, and an unexpected result in a chemical characterization study can stall a submission. This is where investigative chemistry earns its keep. Moving a compound from unknown to tentatively identified is a distinct analytical step, and Jordi Labs, an RQM+ Company, is differentiated in exactly that kind of problem solving. From a tentatively identified structure, the Lumo™ platform uses molecular properties to estimate a compound's analytical response and produce quantification with a documented accuracy range, and because that estimate draws on molecular properties, the precision of the starting structure matters less than it would in a traditional surrogate approach  The second is evidence. Post-market surveillance and clinical follow-up have ceased being paperwork exercises. Regulators and payers now expect a living evidence base, and an AI medical device adds another layer, since model performance must be monitored as data and populations change. Building that monitoring in before launch is far cheaper than retrofitting it under tight scrutiny How integrated execution turns pressure into momentum Recognizing the trend is easy. Operationalizing it is where most organizations stall. This is because integration across regulatory, clinical, lab, and market access functions usually means more vendors, more handoffs, and more coordination overhead. RQM+ built SMART Solutions to remove that friction.  The model comes in two forms: Integrated SMART Solutions gives small and midsize manufacturers unified orchestration across the full life cycle under one governance structure.   Functional SMART Solutions embeds structured leadership inside a single vertical for larger enterprises that need depth in one area without losing alignment to the broader program. Both scale horizontally and vertically as a program grows, without adding headcount or new vendors.  Integrated execution changes how a program runs day to day:  Risks across regulatory, lab, clinical, and market access become visible earlier, before they turn into rework or recalls  Evidence is planned once to satisfy regulatory and payer needs together, instead of twice  Governance runs on clear roles and review cadences, so decisions do not stall between functions  Capacity expands from a focused starting point as the program evolves, without restarting vendor relationships The result is the outcome the forum kept pointing toward, which is that regulatory pressure stops acting like a brake on commercialization and starts working as part of the engine. Building or scaling a device for the EU market in 2026? Connect with RQM+ to pressure-test your regulatory, evidence, and market access strategy before the gaps that surface late turn into commercial setbacks. Let’s make your MedTech program happen.  Frequently asked questions How is EU MedTech regulation changing in 2026?   The EU is advancing a targeted revision of the MDR and IVDR aimed at simplifying requirements and reducing administrative burden, while EUDAMED’s first four modules become mandatory on 28 May 2026. Devices already on the market have until 28 November 2026 to register. Both shifts raise the premium on accurate data and early cross-functional planning.  Why integrate reimbursement and regulatory strategy early?   Because evidence designed late rarely satisfies both regulators and payers. Aligning a reimbursement strategy with the clinical and regulatory plan lets one evidence program serve several needs at once, which protects both the commercialization timeline and the budget behind it.  What makes an integrated CRO different from using multiple specialist vendors? An integrated partner runs regulatory, clinical, lab, and market access work under one governance structure, so risks surface earlier and functions stay aligned. That removes the handoffs and rework that tend to fragment a medical device go-to-market strategy across separate suppliers.  References MedTech Europe. Revision proposal is first step towards fixing Europe’s complex Medical Devices & Diagnostics rules. 16 December 2025. https://www.medtecheurope.org/2025/12/16/revision-proposal-is-first-step-towards-fixing-europes-complex-medical-devices-diagnostics-rules/  European Commission. EUDAMED overview. https://health.ec.europa.eu/medical-devices-eudamed/overview_en  MedTech Europe. EUDAMED reaches a major milestone: mandatory use of the first four modules begins. 4 June 2026. https://www.medtecheurope.org/2026/06/04/eudamed-reaches-a-major-milestone-mandatory-use-of-the-first-four-modules-begins/  #### Women’s Health MedTech Innovators: Are You Prepared for These 6 Regulatory Strategy and Market Access Hurdles? The investment case for women’s health innovation has never been stronger. The global market sits somewhere between $15 and $30 trillion, venture capital interest is accelerating, and public attention has finally caught up to the scale of the unmet need.¹,² Yet companies with the right science, the right team, and real clinical urgency are still stalling out because the regulatory and market access system they’re navigating was not built with women’s health in mind.  The companies that break through treat regulatory strategy, clinical evidence, and market access as a single integrated program from the start, not a sequence of hurdles to clear one at a time. What follows are 6 of the most consequential hurdles in women’s health MedTech, drawn from direct experience across regulatory submissions, clinical programs, and market access engagements.  Hurdle 1: You’re often building without a regulatory map For many women’s health applications, the regulatory framework that would normally guide development simply does not exist yet. Innovators in spaces like menopause management, pelvic floor health, or gynecological diagnostics frequently find there is no established product code, no clear predicate device, and no published guidance that speaks to their device type.³ The frameworks governing medical devices evolved largely from data and design contexts that centered on male or mixed populations. Under 21 CFR Part 884, which governs obstetrics and gynecology devices, there are provisions better aligned to male equivalents than to the female devices seeking clearance under the same code.  The absence of a map is not the absence of a path. Teams that engage the FDA before formal submission to clarify expectations and align on the evidence standard consistently fare better than those who arrive with a completed package and an unresolved predicate problem. Global regulatory compliance in women’s health often starts with building the framework, and regulators who understand the space welcome that conversation.  Hurdle 2: The evidence base was built without you For decades, women were excluded from clinical trials or enrolled in numbers too small to support meaningful subgroup analysis. The FDA restricted women of childbearing potential from multiple early-phase studies from the 1970s through the early 1990s.4 That policy was reversed, but the data gap it created did not disappear.  The downstream effect is that innovators in women’s health are often working without the foundational evidence needed to establish context for their own submissions. Predicate comparisons are harder to draw, and baseline benchmarks may not reflect female physiology.  The FDA’s emphasis on “generalizability” (the extent to which a study’s findings can be extended meaningfully to the intended patient population) has become a defining lens for review.5 Thoughtful clinical trial management that centers on generalizability from protocol design through site selection gives programs a structural advantage. Companies investing in inclusive evidence now are building a competitive position that is difficult to replicate later, because the data have to exist before regulators will accept them.   Hurdle 3: Blanket exclusion criteria narrow your future options  The risk associated with investigational devices is often mitigated through strict exclusion criteria in clinical trial protocols. When these trials are complete and the risk profile is better understood, many companies fail to make the investment to expand trials to study effects on previously excluded patients. Blanket exclusions like pregnancy risk, hormone variation, and certain comorbidities that are common in women may seem like a clean way to reduce confounding. However, they frequently create problems at the labeling stage. A bone health device trial used a hemoglobin threshold based on U.S. population norms that excluded a significant portion of women in Japan, where the normal range is lower.6 The science was sound; the assumption was not.  Strong clinical trial recruitment strategies for women’s health start by pressure testing every exclusion criterion before the protocol is locked. In practice, that means:  Reviewing each exclusion against the intended use population, recognizing that for premarket studies the intended patient population is often refined after the trial is complete   Flagging criteria derived from male or U.S.-only reference ranges for population-specific validation (e.g., hemoglobin thresholds that do not reflect normal values across global female populations)  Evaluating whether a confounding factor justifies exclusion or can be managed through stratification or subgroup analysis, which is especially relevant in women’s health where hormonal variation and reproductive status are often treated as confounders rather than clinically meaningful variables  Leveraging decentralized trials and remote data collection to mitigate geographic bias, provider bias, and site-of-care bias — not only to reach underserved populations, but to improve the generalizability of findings across the full intended use population   Hurdle 4: A broad indication does not guarantee a broad label A related and distinct challenge emerges when a broad indication statement meets a narrow study population. In women’s health, it frequently happens that a device intended for all postmenopausal women, or for the full spectrum of a condition like endometriosis, is studied in a population so restricted by exclusion criteria that the resulting label reflects only a fraction of the intended market.  The assumption is that this can be corrected in negotiations with the FDA. It rarely is. Regulators approve labeling that reflects the population actually studied, and recovering from a mismatch means additional studies, additional time, and resources that most growth stage women’s health companies cannot absorb.  The fix requires discipline early. As part of a coherent regulatory strategy, the indication statement, the inclusion and exclusion criteria, and the labeling target all need to be reviewed together before the protocol is finalized. For a menopause management device with a 10-to-12-year evidence journey ahead of it, getting that alignment wrong early compounds across every subsequent study and submission. Alignment at that stage prevents a negotiation at the submission stage that teams are unlikely to win.   Hurdle 5: Reimbursement treated as a downstream decision A breakthrough device that doesn’t get reimbursed is an expensive prototype. Yet reimbursement strategy continues to be treated as something that happens after regulatory clearance in too many women’s health development programs. A significant portion of women’s health conditions lack established CPT codes or carry reimbursement pathways designed around older clinical frameworks that don’t map onto new device categories.   Pelvic floor devices, remote menopause monitoring tools, and emerging diagnostic platforms for conditions like endometriosis or polycystic ovary syndrome are frequently cleared before any coverage pathway exists for them. Building health economic evidence only after clearance means starting from scratch at the moment commercial traction is most urgent.  Companies making real progress integrate reimbursement planning into clinical trial design from the beginning. That integration looks like:  Selecting clinical endpoints that satisfy both regulatory reviewers and payer requirements simultaneously  Engaging market access consulting expertise before the trial is locked, not after submission  Building health economic evidence into the evidence plan as a primary output, not an afterthought  Mapping CPT code gaps and coverage pathway complexity during protocol development, while study design can still respond to what’s found  Payers and regulators are asking different questions about the same data. Teams that design studies to answer both simultaneously don’t have to choose between speed to approval and speed to coverage.   Hurdle 6: Market access is not a launch activity Regulatory clearance opens a door. It does not guarantee entry. In women’s health, where clinical champions needed to drive adoption may not yet be in established referral networks, getting a product into the right health systems requires planning that starts well before clearance. Unlike cardiovascular or orthopedic devices where established KOL networks and procurement channels are well-established, many women’s health categories (e.g., menopause management, gynecological diagnostics, pelvic health) are navigating health system relationships that are still being created.  The average hospital system onboarding process for a new supplier takes approximately two years.7 For a startup navigating that independently across dozens of systems, the timeline is prohibitive. The companies scaling most effectively identified strategic partners early — established players with existing approved supplier status, health system relationships, and access to key clinical decision-makers in their target market.  Women’s health innovation is increasingly founder-led by people with deep clinical insight and real patient connection, but who may lack the institutional networks that accelerate procurement, trial site access, and key opinion leader engagement. Women’s health innovators are also more likely to be entering spaces where those networks don’t yet exist in the same form, which means building market access infrastructure alongside building the product, not after it. Investors and commercial partners who bring those networks carry access that the company cannot build fast enough on its own.   The Common Thread Each of these hurdles shares a root cause. They emerge when regulatory, clinical, and market access planning are treated as separate, sequential activities rather than a single integrated strategy. Teams that bring those disciplines to the same table early and repeatedly are the ones that reach patients without rebuilding their programs along the way.  Women’s health is not a niche. It is a comprehensive clinical need, a generational market opportunity, and a patient imperative. RQM+’s medical device regulatory strategy consulting services span the full product life cycle, with regulatory, clinical, lab, and reimbursement expertise working as one integrated team.   Building or scaling a women’s health innovation? Connect with RQM+ to stress test your regulatory and market access strategy before small gaps turn into big setbacks. References  Women’s Health Access Matters (WHAM). (2024). WHAM Report: Investing in Women's Health Research. https://whamglobal.org/  Her Health Equity. (2025). Presented in RQM+ Live! #87, “Built for Her: Funding, Fixing, and Fueling the Next Era of MedTech.” March 2025.  Callanan, M., & Kladakis, S. RQM+ Live! #87. March 2025. (Panelist commentary on regulatory framework gaps in women’s health.)  Institute of Medicine (US) Committee on Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies; Mastroianni, A.C., Faden, R., Federman, D., editors. (1994). Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies: Volume I. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK236531/  U.S. Food and Drug Administration. (2023). Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies  Kladakis, S. RQM+ Live! #87. March 2025. (Panelist commentary; hemoglobin reference range example.)  Fayer, M. RQM+ Live! #87. March 2025. (Panelist commentary; hospital onboarding timeline estimate.)  ### Leadership #### Kevin Rowland Kevin Rowland has been with Jordi Labs, an RQM+ company, for over 13 years and currently leads the lab services division. With expertise in materials science, chemistry, and analytical testing, Kevin ensures that RQM+ provides best-in-class lab services to support clients with extractables and leachables testing, chemical characterization, and more. #### Jaishankar Kutty, PhD ​Jaishankar (Jai) Kutty, Ph.D. brings 17+ years of multidisciplinary experience to the cardiovascular and structural-heart space, spanning R&D, Notified Body leadership, global clinical strategy, regulatory policy, and reimbursement-aligned evidence generation. He has helped deliver 100+ worldwide approvals, designed studies that de-risk innovation, and pushed the medtech industry to rethink how evidence should be built, validated, and leveraged. At RQM+, Jai leads regulatory, reimbursement, and clinical-evidence strategy for a global portfolio of next-generation cardiovascular technologies. Previously at BSI, he helped write the playbook for MDR clinical expectations and partnered closely with FDA, CA authorities, and Notified Bodies. A frequent speaker, writer, and RQM+ Live! panelist, Jai is known for his ability to take the snarled intersection of regulation, clinical science, and payer expectations, and make it understandable, strategic, and, occasionally, entertaining. #### Brandy Chittester, MS Brandy has nearly 20 years of experience conducting clinical trials in the medical device and diagnostics space. Her trial experience encompasses US and global studies across multiple phases and includes cardiovascular and peripheral vascular implantable devices, urology, orthopedics, neurology, women’s health, combination products, IVDs, and imaging modalities. Her experience managing full-service MedTech CROs at an executive level and passion for providing high-quality, compliant clinical research services has led to numerous long-term partnerships and a large network of industry professionals. Brandy is skilled in building high-quality, high-functioning teams and thrives on executing trials in ways that work for her study teams, sponsor partners, and sites. #### Torrie DeGennaro Torrie DeGennaro brings over a decade of MedTech experience to her role as Vice President of Scientific & Medical Writing at RQM+. Specializing in clinical documentation, Post-Market Clinical Follow-up (PMCF), and Post-Market Surveillance (PMS), Torrie leads a team of highly skilled medical writers dedicated to supporting clients across the entire product lifecycle including clinical trials, clinical evaluations, regulatory submissions, and post-market documentation. Her leadership ensures high-quality, compliant deliverables that meet evolving global standards and drive successful outcomes for medical device manufacturers. #### Jon Gimbel, PhD Jon Gimbel, Vice President of Regulatory Affairs at RQM+. Jon is actively involved with overseeing the technical aspects of the clinical, post-market and regulatory practices at RQM+. Jon has a Ph.D. in mechanical engineering and over 20 years of device design, regulatory affairs, and clinical affairs experience. #### Noel Keegan Noel Keegan is Vice President, Data Operations at RQM+ Clinical Trial Services. He provides operational leadership and functional oversight of Data Operations, drawing on more than 16 years of experience managing clinical trial data across CRO and medical device companies. His background spans diverse therapeutic areas and study designs in medical device and diagnostics research. Noel has deep expertise in establishing, maintaining, and locking complex clinical databases across multiple EDC platforms. He is recognized for dependable study oversight and strong partner relationships, helping set and uphold standards for budgets and timelines throughout the project lifecycle. A strategic planner and skilled problem solver, he is committed to team growth and to consistent, high standards of excellence within Data Operations. Noel holds an Honors Bachelor of Science in Pharmacology and a Master’s degree in Project Management. #### Dr. John Potthoff With extensive experience in MedTech leadership, John Potthoff, Ph.D., brings strategic insight and a track record of growth to his role as CEO of RQM+. As cofounder and former CEO of Elligo Health Research® and past CEO of Theorem Clinical Research, John’s leadership ensures that RQM+ remains a global leader in regulatory consulting and clinical trials management. He has been a member of the RQM+ board since 2021. #### David Sockolof David Sockolof is Chief Financial Officer at RQM+. He brings 20+ years of finance and operations leadership in global clinical research, including CFO of ProSciento and senior roles at Labcorp Drug Development and PRA Health Sciences. David has led financial strategy, forecasting, resource management, and proposals and pricing across complex, high-growth organizations. He holds an MBA and BBA from The George Washington University School of Business. #### Melissa Orenstein Melissa is the Vice President of People and Culture, bringing over 15 years of HR and talent experience. She leads company-wide initiatives that build strong teams, enhance employee engagement, and shape a positive workplace culture. Her background spans talent acquisition, leadership development, performance management, and employee relations, with a consistent focus on aligning people strategy to business goals. Melissa has successfully supported organizations through growth and change, building scalable HR operations and inclusive environments where employees can thrive. #### Ronnie Mahofski Ronnie Mahofski joined RQM+ in 2015 and currently serves as Executive Vice President of Corporate Development. With deep expertise in strategic account growth, corporate partnerships, and mergers and acquisitions, Ronnie has led multiple successful acquisitions that have strengthened RQM+’s market position. He is a driving force behind the company’s corporate development, commercialization strategies, and operational excellence. Through his strategic leadership, Ronnie ensures that RQM+ delivers customized, high-impact solutions that help clients achieve market success. #### Craig Lunsford Craig Lunsford serves as Senior Vice President, Commercial Operations at RQM+, where he leads enterprise-level initiatives to elevate sales performance, enhance customer engagement, and streamline proposal and contracting processes. Craig is responsible for advancing the commercial infrastructure that supports scalable success—aligning systems, teams, and processes to deliver value at every stage of the customer journey. He plays a critical role in shaping the company’s go-to-market strategy, leveraging data insights to improve win rates, operational efficiency, and client satisfaction. Prior to joining RQM+, Craig held multiple senior leadership roles at IQVIA, including Vice President of Customer Buying Experience, Head of Americas Proposals & Contracts, and Senior Director of Sales Force Effectiveness. Throughout his tenure, he was instrumental in transforming commercial operations on a global scale, implementing innovative solutions that optimized sales performance and deepened customer relationships. With more than 20 years of experience in finance, sales operations, and commercial effectiveness, Craig’s strategic vision and analytical mindset helps driving growth while delivering a seamless client experience. #### Frank Maier Frank Maier serves as Vice President, EU Operations at RQM+ with over 15 years of experience in the medical device and IVD industry. While demonstrating profound knowledge of regulatory requirements like ISO 14155, ISO 20916, (EU) MDR 2017/745 and (EU) IVDR 2017/746, he provides corporate-wide strategic, operational, and functional leadership of RQM+ for Europe and the associated business operations. Frank´s in-depth knowledge includes a wide range of therapeutic areas in both pre- and postmarket clinical investigations in the EU and APAC region. #### Sandra Bausback-Aballo Sandi Bausback-Aballo serves as Vice President, Medical Affairs at RQM+ where she oversees the global Clinical Safety team and medical consultants responsible for the monitoring of safety related issues to patients and end users with a keen eye on regulatory compliance. She is a Registered Nurse with extensive experience in the clinical and medical device manufacturing space and is passionate about patient and public safety.