2021 was another big year in the European regulatory realm as EU MDR and IVDR implementation continued to roll out. Let’s take a look at the highlights and lessons learned that we can apply as we go into 2022.
Notable Events in 2021
MDR Date of Application
26 May 2021 marked the MDR date of application, which triggered the requirement for post-market surveillance (PMS) for all devices regardless of whether they are in the MDD transition period or have been certified under MDR. This means all medical devices on the market are now required to comply with post-market surveillance requirements.
IVDR Progressive Rollout Adopted by EU Council and Parliament
The 26 May 2022 IVDR date of application did not change but instead gave some additional transition time depending on the classification. Because the date of application remains in effect, post-market surveillance as per the IVDR will be required for all IVDs starting in May 2022.
The transitional arrangements provided by article 110 have been amended, allowing a progressive rollout of the IVDR according to product risk:
- Class A, self-certified - 26 May 2022 (no change) with a sell-off period until 26 May 2025
- Class D - 26 May 2025 with a sell-off period until 26 May 2026
- Class C - 26 May 2026 with sell-off period until 26 May 2027
- Class B and A sterile - 26 May 2027 with a sell-off period until 26 May 2028
For in-house devices (i.e., LDTs), the commission proposed to defer the application of most of the conditions to be met by health institutions making in-house devices by two years until 26 May 2024.
Although this postponement has been much awaited by many manufacturers, it does not actually provide much more breathing room because there is so much to be done, and work needs to be already in progress to have a good chance of meeting the new submission deadlines. In order to stay compliant with IVDR and meet the application requirements, manufacturers should be actively working on their submissions now regardless of the class of the device.
MDR Expert Panel Opinions
The first expert panel opinion was published in June. This was subsequently removed at the request of the notified body, but it has since been reinstated with the product name redacted. Many in the industry were surprised by the opinion, which was more stringent than they expected for a legacy product. This inaugural opinion set the tone that clinical evidence will be closely evaluated by regulators and warnings with respect to “no grandfathering” when it comes to clinical evidence requirements for legacy products.
Two further expert opinions were published in 2021, one under orthopedics and one under circulatory system. Each expert opinion provided further insights and potential surprises into the workings of the expert panels.
IVDR Scientific Views
The first scientific view related to IVDR was delivered by the expert panel in November.
It appeared much less challenging than the consultation with the MDR device panels. Since then, a number of other, generally positive, scientific views have been issued. Unlike the MDR, the purpose of the IVDR expert panel consultation is to develop common specifications for the first device of its type (for Class D without common specifications).
Therefore, under IVDR, the manufacturer's documentation is received by the expert panel before the notified body has had a chance to assess it. Although the IVD expert panel did not raise significant concerns, it is anticipated that many of the gaps they identified will raise questions during the subsequent notified body review.
The release of MDCG 2021-24 had a major impact on manufacturers of some types of spinal implants. Most spinal devices that do not preserve motion were expected to be considered Class IIb based on a position paper issued by Team NB in 2018. The guidance unexpectedly classified several devices, including all fusion devices, motion-preserving, and even some other components such as hooks and other devices placed in the disc space (regardless of whether or not they are motion-preserving) as Class III, though a few stayed IIb. As devices that have been on the market for a long time with no novelty of design or manufacture, many of them are also considered well-established technology (WET) as proposed by the Team NB position paper. WET devices are exempt from certain regulatory requirements as listed in Articles 52(4) and 61(6b). However, as both Article 61(10) and MDCG 2020-6 indicated, the exempt devices are not the only WET, and not all WET are exempt.
All Class III and non-exempt Class IIb implants must have a successful technical file assessment by a notified body before they can be certified for use in the EU. Class IIb exempt WET devices (Articles 52(4)) can be placed on the market based on an appropriate sample of the technical documentation. Manufacturers now face a higher burden of sampling and other technical documentation requirements—although the change does not directly affect the required quality or quantity of clinical evidence that must be presented.
EUDAMED Registration Modules Became Active
The rollout of EUDAMED started in 2021, and the full implications remain to be seen. Given that EUDAMED registration will create an additional administrative burden for most manufacturers, we recommend that they get started sooner rather than later. Although it’s still new, we expect to see challenges related to aligning internal systems with the EUDAMED modules. Early reports from both manufacturers and notified bodies confirm this. Currently live modules (three of the six planned) are:
- Actor Registration
- UDI/Devices Registration
- Notified Bodies and Certificates
Lessons Learned in 2021
With such a busy year for regulators and manufacturers alike, it’s no surprise that many valuable lessons were learned along the way.
Because so many more IVDs require certification under IVDR that were previously able to self-certify under IVDD, there is a huge volume of work to be done, and many manufacturers have been facing a steep learning curve. Grandfathering is not allowed—no matter how long your device has been on the market. This may mean that additional testing may need to be undertaken—or clinical evidence or other documentation generated—for devices that have been on the market for many years.
So far, most findings raised by notified bodies are related to performance evaluation requirements not being met—in particular, those outlined in Part A of Annex XIII of the IVDR. Take a close look at these requirements when preparing your documentation to avoid these types of findings for your submissions.
The bottom line is that all manufacturers must comply fully with the regulation. Submissions take time, and time is running out.
Intended Purpose Statements
All IVDs must have a medical purpose statement and clinical evidence that aligns with that statement. The medical purpose statement should be detailed and correct as it influences the classification, which impacts the entire application. Many (possibly most) intended purpose statements for IVDs are not compliant and will need remediation before you can even get a quote for a conformity assessment.
Intended purpose statements are also being closely scrutinized under MDR to ensure alignment between the stated purpose, the clinical evidence available, and the clinical risks and intended benefits of the device. Intended purpose statements must include indications for use for medical devices where these are applicable. This includes a description of the intended patient population, specific disease condition, anatomic location, end stage, and severity of disease; specificity is key. Not all devices, however, have an indication for use (as confirmed by MDCG 2020-6).
More Emphasis on Evidence of Clinical Benefit and Overall Benefit-Risk Conclusion
Regulators are expecting manufacturers to describe and show evidence of the clinical benefit for patients. They must demonstrate not just that the device does what it is intended to do, but that there is a benefit to the patient, and that this benefit is acceptable in relation to other available treatment alternatives and associated clinical risks. EU regulators are much less likely to accept assumptions of device safety based on passive post-market surveillance, and a lack of reporting or an absence of evidence does not necessarily mean there are no problems.
Meta-Analysis of Data
More notified bodies are asking manufacturers to provide meta-analyses of their data sets to ensure consistency in the conclusions drawn from studies. Bear this in mind when preparing submissions, and consider proactively providing this type of analysis, ensuring you have appropriate biostatistical and clinical expertise involved.
Challenges of Writing SSCPs
A summary of safety and clinical performance (SSCP) is required for Class III and implantable devices. SSCPs are intended to be read by practitioners and, in many cases, patients. Many manufacturers have learned the lesson that writing for a lay audience is not so easy. It is not just a case of using smaller words but also ensuring that the message is understandable to the layperson, addresses issues relevant to them, and the content is not distorted by attempts at simplification. Some notified bodies are requesting not just algorithmic scores of readability but also tests involving actual laypeople. These tests often flag requirements for revision. Medical writers are used to writing to a more technical audience and are still learning how to adapt to a lay audience.
What to Expect in 2022
With 2022 already in full swing, it’s time to prepare for what we already know is coming.
Date of Application for IVDR in May
All IVDs currently on the European Union market will need to adhere to IVDR procedures related to vigilance, PMS, registration of economic operators, and device registration from 26 May 2022. Class A devices, including instruments, make up a significant proportion of the IVD sector and will need to be ready by 26 May 2022. All new devices to market after 26 May 2022 must also comply with IVDR in full.
Guidance for PSURs Will Be Published in Q1 2022
Early drafts of the guidance document about periodic safety update reports (PSURs) included requirements for updated benefit-risk conclusions based on the state of the art and more emphasis on clinical performance and benefit—as opposed to safety—than was originally anticipated. This implied at least some revision or update to the entire clinical evaluation and not just a review of data relevant to complaints and adverse events. It has been suggested that this may be toned down in the final guidance document, with greater emphasis on safety as implied by the name. We expect the first PSUR guidance to be released for medical devices in early 2022, with IVD guidance to follow.
The CORE-MD initiative kicked off in April 2021. In 2022, we hope to see some movement on the first work package, which includes recommendations for standard clinical outcome measures for some types of high-risk medical devices. Ultimately, we look forward to a consensus on what clinical outcome measures for these devices should look like.
Notified Body Initiatives
Notified bodies continue to build internal resources to meet the demands of EU MDR and IVDR certification. Competency requirements are higher than ever and increasingly specific to device technology and clinical specialisms, driving demand for more reviewers. They are also investing in IT systems that allow them to communicate more efficiently with manufacturers and EUDAMED interfaces and create reports more efficiently.
Take Action in 2022
No matter what type of device or IVD you manufacture, it is no longer possible to sit on the sidelines if you want to keep your products on the market and maintain compliance. Now is the time to take the next steps you have been avoiding. If you’re feeling overwhelmed or don’t have the capacity on your team to do the work, we’re here to help.
With many manufacturers past the planning stages and well into execution, RQM+ is offering practical tips for efficient implementation. Our on-demand webinar, “Best Practices and Processes for Integrating CERs and Post-Market Surveillance Under EU MDR,” uses real-world scenarios to show you how to share information, streamline processes, and ensure consistency across your technical documentation. Click here to get access now.