MDR Certification Challenges Associated with Clinical Evidence

Interview by Michal Pallo (Department of Drug Design and Pharmacology, University of Copenhagen) with Michael Vent (BEO BERLIN) on the challenges for manufacturers associated with the new requirements for clinical evidence and evaluation under MDR.

The following questions pertain to manufacturers who required MDR consulting services during their transition for eventual device re-certification under MDR.

Could you observe a trend in when manufacturers initiated the process of the MDR transition?
Yes, most of our clients started 9-12 month before May 2020. Some of them needed to be reminded, most of them asked for clarification. A considerable number became nervous because there was a fearsome discussion about the MDR in the media. We had a lot of talks and held several seminars to clarify details and to calm them down. In the end, for most of them, it turned out not as dramatic as they expected. They simply needed to start in a timely manner to enable a smooth transition.

Do the requirements of the MDR on clinical evidence, use of higher quality clinical data and rules on demonstration of equivalence represent issues for the manufacturers in transition? If yes, could you specify those issues?
Yes, in practical implementation, the requirements have increased considerably. Even if MEDDEV has not changed because of MDR, some uncertainties have arisen because of MDR itself. The reason was and still is that in MDR some aspects are handled differently. Especially in the equivalence discussion, we must now look much deeper into the equivalence product. We need very precise knowledge about the mode of action and the structure. These aspects have always had to be considered, but the depth of information was different. Some inconsistencies between MDR and MEDDEV 2.7.1 still cause correction loops.
For example: equivalent devices used under similar or same conditions; exceptions concerning biocompatibility if minor components are in contact with intact skin only; etc.
Another problem is the lack of routine in the new evaluation procedure. Depending on the Notified Body the manufacturers work with, the focus is on different aspects.

Do manufacturers have sufficient clinical data and evidence to close the gap between MDD and MDR?
Normally, yes. It depends very much on the type of product whether clinical data with a sufficient level of evidence can be found. However, if there was already no adequate data available under MDD conditions, it is even more difficult under MDR. In addition to the purely clinical data, it is also very important to exhaust the available possibilities through laboratory tests. For many products there are standardised requirements which can be found in corresponding product standards. Clinically relevant safety aspects can also be found there. So, if conformity can be proven at this point, many information gaps can be closed. This plays a particularly important role when it comes to the equivalence discussion, already mentioned above.

Could you observe a trend in which device classes and categories were affected the most, did not have sufficient clinical evidence and required a new clinical investigation or other source of clinical data? If yes, why?
Yes, absolutely. For many Class I and IIa product types there is no clinical data of high evidence. One reason for this is the regulatory tolerance for the low risk class. It was widely accepted to provide some clinical data of low evidence or even no clinical data at all. This will change. Not least because of the difficult economic situation in this segment. Often there is simply not enough money for clinical investigations. Even small clinical trials usually cost a 6-figure amount. This money is usually not available to  smaller manufacturers in particular. Manufacturers whose product was a Class I product under MDD and becomes an Ir or IIa product under MDR, have been hit the hardest. For these manufacturers, the verification by a notified body is a new hurdle and the notified body must insist on the compliance with the requirements out of their own interest, because the notified bodies also have to meet stricter requirements.
The transition for high-quality Class IIa and IIb products should be the most relaxed one. These  manufacturers already have had to meet high requirements in the past. They were monitored by notified bodies and they have an appropriate organisational structure.

Were additional clinical investigations or clinical data sources required, or were the data from PMS rather sufficient?
Data from PMS is absolutely needed to make a proper clinical evaluation. A lot of clinical safety aspects refer to technical and usability safety. So, data from non-clinical safety reports definitely support the clinical evaluation. However, evidence based clinical data is still necessary. If new data need to be generated by clinical investigations, depends on the individual situation. For a standard device, we usually find sufficient clinical data in data bases like embase, pubmed, google scholar etc.

Are there other specific approaches that manufacturers used, or you advised them to use, to close the gap between MDD and MDR?
Actually, no. The gap between MDD and MDD can be managed, more or less, like every other regulatory gap. It should start with the definition of a medical device and its classification. The next steps are the risk management file and the clinical evaluation file. From our perspective, this is an efficient way for the transition period.

Are there other major challenges associated with clinical evaluation and clinical evidence?
There are surely a lot of individual situations and challenges to fulfil the requirements. However, the highest, according to our experience, is the higher review-level of the notified bodies and authorities. Data and reports that passed the reviews in the past, are very often evaluated differently under MDR.

What about your experience with devices moving to a higher class (e.g. from class I to IIa)?
The devices that move to a higher class certainly face the hardest transition. Even if the companies were audited by their competent authority, the audit by a notified body is by far harder to pass. This is true not only for the quality of data but also for formal aspects. Sometimes the manufacturer collected sufficient data but didn’t follow very strictly formal aspects when they created their reports. So, besides the new requirement of having a certified quality management system, the technical file including test reports, discussions, justifications, rationales and other verification and validation protocols very often must be adjusted.

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