As the medical device industry addresses EU MDR requirements, aspects of the regulation will likely be implemented by other global regulatory agencies as they seek to harmonize.

Medical device experts Mark Agostino (Redica Systems) and Alison Sathe (Regulatory Mark) discussed this aspect of the EU MDR during the Oct. 28 virtual panel discussion, “Changing Medical Device Regulations.” Redica Systems Senior GMP Quality Expert Jerry Chapman moderated. 

Webinar ad - download

The following has been lightly edited for clarity. Part I covered EU MDR requirements for quality management systems and Part II looked at postmarket surveillance.

EU MDR and Intended Use

Jerry Chapman

Chapman: Regarding products that have U.S. FDA 510(k) clearance, the EU MDR does not give any clear requirements for intended purpose. How can manufacturers write intended purpose so that it does not affect 510(k) clearance in the United States?

Alison Sathe

Sathe: That is a really good question because your indications for use, intended use, and intended purpose, are all documented in your technical file on the EU side, and they have to align. There is also a little bit of nuance in the United States between indications for use and intended use. Then, on the EU side, we have the intended purpose, which hopefully aligns with your intended use for your product in the United States. If it does not, then that is an issue that will come up because of labeling.

That might require two different types of labeling. You might have to have labeling in the United States to comply with your 510(k). And perhaps you have a different label for your EU submission, because when you are thinking about that intended purpose in the European Union, that has to be supported by the clinical evidence. That is something where if you have certain clinical claims, i.e., if you have intended purposes that you are putting within your labeling, it is very important. Your Notified Bodies will check. So, your technical documentation should reflect the clinical evidence to support them.

Mark Agostino

Agostino: Just to build upon what Alison said, you are going through the design validation studies, which are there to validate the intended use. So a lot of it is the way you structure your clinical studies and design the endpoints of your studies, and getting into usability, and to help identify, create critical tasks, and then show that those critical tasks are appropriately under control and understood.

These are all the elements that are all linked. So as you go through the work for the Design History File (DHF), and, ultimately, to get to 510(k) clearance, think about the standard that is a parallel path when it comes to the EU MDR and the technical file. Again, it is getting into what claims and what clinical endpoints you are going to have in place to meet that are going to support your intended use.

A big part of this is understanding that once you have your verified design that you are going to incorporate into your design validation studies that all the evidence supports it.

EU MDR: Harmonization Coming?

Chapman: I am a Senior GMP Quality Expert at Redica Systems, but my expertise is in pharma, not devices. And it occurs to me as I listen to this that there are some commonalities, but there are some pretty big differences too. The whole idea of intended purpose is not something that we think about in the pharma world. It is just different.

The one thing that is the same is that when regulations are made in a regulated industry by some regulator that the other regulators around the world sit up and take notice. So, I guess my question is, as a result of the MDR, do you anticipate other regulators revising their regulations as well? 

Sathe: I think overall the trend is toward more data right across the board globally when it comes to submissions. In previous jurisdictions where there were minimal regulations, we are seeing more acceptance of the CE mark or 510(k) or FDA clearance.

So, the trend is certainly toward more data and more rigorous applications. I think it is interesting because, of course, with the EU MDR, there was this paradigm shift. We used to see companies choose to go to Europe first and then follow up with submission in the United States second. Now companies, particularly, startups and smaller companies, are choosing to go to the United States first and then follow on with an EU MDR submission. A lot of that is just the newness of the EU MDR. Everyone is still kind of getting a handle on that globally. 

From the FDA side, we are seeing a nod to ISO 13485:2016 Medical devices — Quality management systems — Requirements for regulatory purpose where they have said for a number of years now that there was going to be some integration with the ISO standard. Of course, I think originally, they had said 2018, and then 2020, but then the pandemic happened.

But I think for all of the regulatory professionals, we would all say we like harmonization in that it makes it easier to have a more global approach.

Agostino: Also on top of that, what I realized as you go into different markets, such as Australia which has a mutual recognition agreement (MRA) with the European Union to adopt a lot of the elements of the EU MDR. So you already have that synergy developing between Australia and the European Union. China is adopting a lot of the elements of ISO 13485. You have Saudi Arabia that has its own regulations now, and they have actually gone even above and beyond particularly for unique device identifiers (UDI) than even what the European Union has done.

The EU MDR is actually kicking off a lot of changes around the rules and regulations worldwide. Also, Brazil is another one that is going through a lot of changes with its ordinances and so forth. While there are still differences, there is also a level of harmonization that is developing.

ISO 13485 is sort of going to be somewhat of the backbone to that. But I think that you are going to still have labeling differences and other nuances among each of the different countries. But a lot of the higher-level quality management systems are in the end going to move toward ISO 13485 because a lot of the major countries in the different regions around the world such as your Chinas, your Australias, your Koreas, and your Saudi Arabias…they are going to be leaders for those different regions. You are going to see a lot more harmonization as time goes on.

[Editor’s Note: In the video clip below is an expanded discussion on global regulatory harmonization of medical device regulations post-EU MDR.]

U.S. versus EU Registration

Chapman: Alison, you mentioned the paradigm of going to Europe first and how that is shifting. Could you comment a lot more about registration of devices in the United States versus the European Union and how the EU MDR has changed that?

Sathe: I think there are a lot of reasons for that. Possibly, one of the reasons that small or mid-sized companies are choosing to do that is due to infrastructure-related processes. In the United States, you have the requirement for 21 CFR 820 for most devices but not all. Some are exempt, but there are specific provisions that apply to those.

And then, of course, you have your registration process. So that is either establishment registration and listing, a premarket submission like de novo 510(k) or premarket approval. And that process is a little bit more straightforward for a lot of U.S. companies that we deal with and some of our global clients as well. With EU MDR you have that extra step where you do have to have that ISO 1345 certification, which is no small feat. It takes time to do that and get your certificates and all of those things.

And the flexibility of the 510(k) paradigm does make that an attractive option for a lot of companies to go to the United States first when you are looking at substantial equivalence determination. Now, I will say 510(k)s over the last 20 years have shifted enormously. There used to be very little documentation that was submitted in 510(k)s. Clearly, FDA has reorganized. Last year about this time, they kind of finished their reorganization. The requirements for 510(k)s have continually increased.

Agostino: To me it just comes down to predictability. I think the FDA approach is much more mature and battle-tested, and there are a lot more devices going through the whole process for people to get a better understanding around, and sort of anticipating what they need to do and where they need to conform in order to get their product to the market. I think that is one of the underlying challenges of EU MDR in that it is so much that affects so much. And then at the same time, that makes it just a level that is not very predictable.

[Editor’s Note: Part IV will examine requirements for combination products and how to train employees on EU MDR requirements.]

[Related: Did a meeting force you to miss this webinar? You can download the full recording here.]

Webinar ad - download

Get a Demo

We’ll can show you insights into any of your key suppliers, FDA investigators, inspection trends, and much more.

Request a Demo