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.
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.