Mark Cabonce, Principal Toxicologist03.10.23
Editor’s Note: This column was written before the European Parliament voted Feb. 16 to extend the MDR transition period.
On Dec. 9, 2022, Europe's Medical Device Coordination Group (MDCG) proposed extending the deadline for current and future medical devices to comply with the EU's new regulatory guidance. The EU's Medical Device Regulation (MDR 2017/745) was introduced in 2017 and took effect in May 2021—after a four-year transition period. The original date by which all medical devices had to attain conformity and certification under MDR was May 26, 2024. But that date appears to be in flux after the MDCG's recent proposal.In June 2022, European health ministers began discussing extending the deadline, citing notified bodies’ (NBs) “insufficient capacity … to certify medical devices in accordance with the MDR” and device manufacturers’ low levels of preparedness. These challenges, the ministers said, could potentially threaten patient access to innovative medical devices across Europe.
A closer look at the data illustrates the scope of the problem. The number of designated NBs in Europe has increased from 30 to 36 since June 2022—and another 26 applications are being processed—but a lot of work remains. As of October 2022, NBs had received more than 8,000 applications from manufacturers and certified almost a quarter of them under MDR. A recent survey of notified bodies estimates the number of certified devices could rise to 7,000 by the May 2024 deadline, at the current rate of issuance. That's encouraging, but it's only a fraction of the 22,793 valid certificates set to expire in 2024.
Given the application backlog size and scope, European manufacturers can most likely expect some reprieve—whether it is a deadline extension or some other mechanism. But what does that mean for their current timelines and processes?
Good News for Manufacturers?
The MDCG showed foresight in recommending the transitional deadline extension. It clearly recognized that certification is taking longer than anticipated under MDR and took steps to alleviate the burden on NBs. That is commendable leadership. But it does not mean manufacturers can slow down or rest on their laurels. There is absolutely no reason to relax. Instead, manufacturers can best use the extra time to double-check their data and resolve any known information or documentation gaps.The MDCG is proposing staggered deadlines instead of a blanket one. Conformity assessments for class IIb and class III devices (those with the highest risk levels) would fall sometime in 2027, with lower risk devices (classes IIa and I) following in 2028. Staggering deadlines like this allows manufacturers to prioritize submissions based on patient risk (high to low risk).
From a toxicologist's viewpoint, high-risk exposures are typically associated with high-risk health concerns. So prioritizing higher risk devices ensures patients have continued access to devices already on the market, and quicker access to anything new or innovative that may be in development. Extending the deadline for lower-risk devices to 2028 helps clear a path in the NB's queue. It is likely high-risk devices will still compete with others—assuming low-risk submissions already in the queue would not be deprioritized or displaced—but it gives NBs a dedicated time frame to focus on high-risk devices with fewer interruptions.
For manufacturers of class IIb and III devices, a deadline extension also gives them time to rethink their strategy. It is conceivable that manufacturers rushing to meet unrealistic deadlines may fail to address everything. Regulators expect that biocompatibility, manufacturing, quality systems, and clinical endpoints are sufficiently addressed so a decision on patient safety can be made. When deadlines get too tight, reporting quality and/or organization of supporting data can suffer if it is forced to fit into generic reporting packages. A transitional deadline extension would be a gift for manufacturers because it would allow them to address potential shortcomings and provides a more probable path to regulatory success.
How Did Industry Get Here?
When the number of certified NBs dwindled from 125 before MDR to around 25 immediately after its implementation, critics scoffed. They noted MDR's focus on complete chemical characterization and the growing confusion about the roles of competent authorities, notified bodies, and authorized representatives. Skeptics also pointed to the European Medicines Agency's (EMA) revised oversight responsibilities as another layer of bureaucracy that would inevitably lengthen an already bogged-down regulatory process. But those are not accurate characterizations of Europe's current process.Certainly, a bottleneck of submissions exists, but it’s unfair to point fingers. Fully certified NBs under MDD (MDR's predecessor) had to be re-certified under new guidelines they may not have seen in advance. No NBs were grandfathered in under MDR, so everyone had to start from scratch. This was always going to create an incongruent number of NBs pre- and post-implementation. It is unclear whether European lawmakers expected those numbers to be equivalent.
Add to that an entirely new risk assessment standard including new safety requirements and it's clear that very few people correctly anticipated how much MDR would shake things up. It's only in practice that the full impact of a fundamental change like MDR comes into focus, and we are beginning to see the real-world challenges it presents. Could a delay be foreseen? Sure. But the degree of the delay could not have been predicted and it is still unknown. Depending on the medical device class, manufacturers could have until 2028 to submit their devices, but that still may not be enough time.
Streamlining Submissions
Europe needs more NBs. Period. More NBs need to train high-quality reviewers efficiently and comprehensively. A band of reviewers who know how to read, interpret, and apply the standards logically would be helpful. Those with experience communicating expectations to manufacturers in clear and actionable ways would be even more valuable.But manufacturers have an important role to play, too. Manufacturers must focus on the quality of their submissions. A 10,000-word submission may be long, but it’s not necessarily comprehensive. Word count doesn't determine quality. Manufacturers must compile submissions in a logical, easy-to-follow way that puts all the information reviewers need at their fingertips.
Submitting coded zip files containing hundreds of other coded files is asking for trouble. Countless references to obscure annexes are another way to slow things down. Reviewers don't have the luxury of sitting down with manufacturers to explain where to find various data points. To streamline submissions, manufacturers should tell a story about their devices. The story cannot be simplistic—it must showcase expertise, after all—but there is also no reason to overcomplicate things.
A device's story should highlight its safety features and disclose potential risks. Biocompatibility data is critical but so is information about materials used and the manufacturing process. Most importantly, any claims made throughout the device's story must be verified and documented. Devices claiming to be “medical grade and safe,” need scientific support. If a manufacturer has a clinical team conducting post-market surveillance and no health issues are reported, that can be critical information in the right context. Specifically, if a device is being measured for one endpoint (immunogenicity) but not another (irritation and sensitization), reviewers will consider that when determining safety claims veracity.
Manufacturers should not rely solely on their submission summaries to make a case for patient safety. The NBs are searching for or requesting documentation that supports any and all summaries. The extra time from an MDR transitional deadline extension is the perfect opportunity to refine and, if necessary, rewrite a device's story.
How Can Laboratory Testing Partners Help Device Manufacturers?
When submission deadlines are extended, timelines must be adjusted. Laboratory testing partners can help accommodate those timelines to account for additional testing or quality measures. Testing partners can also perform gap analyses to identify data shortcomings and ensure a device is scheduled for additional testing. The most valuable role a testing partner can play when a submission deadline is extended is to ensure documentation is complete and comprehensive when the device is ultimately reviewed.When choosing a potential partner, manufacturers must be diligent. Do not hesitate to interview potential partners to get a feel for personality fit and staff credentials. Ask about their policy on unknown compounds and how they address additional information requests. And be wary of partners that cannot or will not provide references. A good lab testing partner is one that manufacturers can trust to get things done on deadline and within budget. Today's medical devices are too important to leave in inexperienced hands.
A Final Word
The MDR transitional deadline is likely to be extended due to the growing backlog of certified devices. But the backlog is more than just a manufacturing headache. It also means patients using high-risk devices or environments in which novel or innovative devices or diagnostics are required, may be forced to go without the products. Both scenarios compromise patient safety, which is unacceptable.Clever manufacturers are choosing their testing partners now, despite a potential change in the submission deadline. That will ensure their devices will be ready for regulators when it's their turn.
Mark Cabonce, M.S., DABT, is a principal toxicologist with a focus on medical devices and combination products. He was a toxicologist managing regulated in vivo and in-vitro acute toxicology studies, assessing formulation dossiers for GHS classification and labeling, and preparing risk assessment in support of domestic and international product registrations. He earned a M.Sc. degree in biology from St. Louis University and has been a diplomat of the American Board of Toxicology since 2005.