On September 23-24^th, the largest gathering of regulatory professionals in the world took place at RAPS Convergence 2019 in Philadelphia. RAPS (Regulatory Affairs Professional Society) covers the fields of pharma, biotech, and most important to me, medical devices. Right now is as great a time as ever to converge and discuss all things regulatory with other medical device folks. In fact, I kept hearing this year’s convergence contained a huge number of medical device attendees. The reason why is clear to me with the EU Medical Device Regulation (MDR) now less than eight months away, and hot topics like artificial intelligence. The medical device regulatory landscape is changing faster than ever and we need to keep up.

Here are my top 5 takeaways:

1. MDR is not only coming, it’s already here and resourcing is a problem.

May 26, 2020 is fast approaching and the looming question is whether enough resources are available to maintain the status quo of medical devices entering the European market. Currently, only five Notified Bodies (NBs) are designated under the MDR. By next May, the number is predicted to reach 15-16. Simply doing the math of this scenario reveals there are not enough NBs to cover transitioning products for re-certification, and re-classified and new products for certification. The European Commission (EC), which is implementing the MDR, is sticking to the timeline. So what will happen? The rumor mill is churning and possible outcomes are being contemplated. Will there be an 11^th hour extension of the Medical Device Directive (MDD)? Is it possible that Member States (i.e., individual nations) will take matters into their own hands and implement work-arounds to the MDR? Or should the EU health system and patients simply prepare for a big reduction in choice of available products if manufacturers and NBs have to pick and choose what gets CE marked. The biggest rumor is the EC has a Plan B in the works, but will not reveal it until late in the game. The best industry can do is ensure they are as prepared as possible from both a regulatory perspective and the business side to handle any possible outcome.

2. Yes, there is the MDR—but wait, what about IVDR? 

The In Vitro Diagnostic Medical Device Regulation (IVDR) gets implemented two years after the MDR, but the changes are greater and the resource situation may be direr. Under the IVDD, 20 percent of IVDs had NB involvement; under the IVDR that number will shoot up to 80 percent, but with fewer NBs to handle the load. There are 22 NBs currently, and only eight are in the process of certifying to IVDR. This should be a loud and clear message that manufacturers wanting to enter or maintain their business in the EU should start planning now. On the bright side, IVD manufacturers will be able to look to the earlier implemented MDR for lessons learned. In particular for all of the overlapping issues such as dealing with Economic Operators, UDIs, EUDAMED, and changes in NB auditing practices. It will be valuable to pay close attention to the MDR.

3. Communication is key to any healthy relationship—that includes yours with the FDA.

Communicate early, communicate often. The review process for your regulatory submissions should start much earlier than file submission. The more familiar the FDA is with your product and strategy, the more smoothly the review will go. Look to the 513(g) for classification questions and remember there are no limits to the number of pre-subs a manufacturer can have. Take advantage of this option when appropriate. With tighter internal deadlines and metrics to meet, the FDA simply doesn’t have the time to familiarize themselves with your product and testing approach while the clock is ticking. As a result, there will be more time spent on clarifications and potentially re-submitting data, which will prolong review time.

A recently added level of communication assists the 510(k) review process and is known as the “Day-10 call.” This is a planned call offered by the FDA approximately ten days after an Additional Information request is issued. The goal is to ensure deficiencies are understood and to help submitters determine if a Submission Issue Request meeting is needed. Manufacturers who have used this call have had very positive experiences.

4. Artificial Intelligence (AI) and Machine Learning (ML)—the future is now.

My main takeaway for this topic includes that data quality is the key. The data curated to train your software should be the most important input into the software development. As well, when managing change, it is useful to implement an AI/ML specific procedure in your quality system. This will become a central resource in the total product lifecycle approach. There is currently a lack of published official guidances and standards on this topic. This will eventually change, but in the meantime, there are two recommended resources for further education. From China, a draft guidance document with the translated title, ‘Deep learning assistant decision-making medical device software review points.’ (Make sure your translate function is turned on.) There is also an FDA published white paper from April 2019 entitled, ‘Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD).’ Lastly, as an interesting exercise examine the automotive industry for examples of how intelligent products already exist and the impact they have had on industry standards. There may be lessons learned for the medical device industry.

5. Lastly, the golden nuggets of information.

The RAPS Convergence was a wonderful opportunity to gain information and knowledge from those in the know. Here are some interesting pieces of advice I learned in no particular order:

• With too few guidances available, NBs are often in disagreement between themselves about how to interpret the MDR. If you experience an undesirable outcome you do not agree with, do not be afraid to go up the chain of command to the NB headquarters first, and then to the Competent Authorities themselves. The key here is to use objective, scientific evidence. The more you have, the stronger your case will be.
• During the Pre-Sub process with the FDA it is sometimes OK to ask additional questions outside the originally submitted set. However, for the FDA to respond, these questions should be related to the original submission, as the FDA doesn’t like surprises. The best way to deliver these additional questions is to include them into the slide deck you are preparing for the meeting to give some advance notice of the questions. Keep in mind the FDA is always within its right to decline answering additional questions.
• This issue I heard over and over again for both the MDR and IVDR: Do not underestimate the impact of Economic Operators to your organization. If your company doesn’t have a plan for this, start researching, understanding, and planning for it now.
• For the MDR, when choosing between an MDD harmonized standard and the state of the art standard, try to comply with both. If you can only pick one, choose the state of the art and provide justifications.
• We should all get “risk-based approach” tattooed somewhere! Consider these words during every decision you make throughout the product lifecycle and regarding your quality system. This will help you identify what is truly important and will guide senior management to resource appropriately.
• Here’s a small tidbit I found interesting regarding Human Factors and Usability: It is always a good idea to include non-trained users in a Summative Validation study focused on the device training program. This helps manufacturers predict outcomes of non-trained users in real-world situations.

There are many more great experiences and learnings from RAPS Convergence that go beyond this article. The only way to truly experience it is to go to the event yourself. See you there next time!

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Deborah Pinchev is the Toronto QA/RA manager at StarFish Medical.