The lack of any grandfathering provisions is one of the biggest hurdles the MDR has put in front of manufacturers willing to transition their devices to the new legislative regime, and probably to the entire system, including Notified Bodies and national competent authorities.
To shed some light on requirements and expectations for devices currently CE marked under one of the directives, the Medical Device Coordination Group has recently published a couple of guidance documents. The first one is MDCG 2020-6, published in April and discussing the requirements in terms of clinical evidence for those devices. This is a quite extensive and dense document that, between the other things, for the first time introduced a formal definition of “legacy devices”, i.e. all devices previously CE marked under MDD or AIMDD. Recently the Medical Device Coordination Group has published additional guidance for devices to be transitioned from the current regime to the MDR, MDCG 2020-12.
The document is focused on devices incorporating a medicinal substance or TSE susceptible animal tissue. Especially in the area of drug-device combinations, some guidance was long awaited and some clarity absolutely necessary. And, although we now know more than before, we cannot say that everything is perfectly clear at this stage.
Let’s start from the devices incorporating a medicinal product. The requirement in MDR Annex IX(5.2) is for a consultation to be conducted with a medicinal product authority or with EMA for devices containing a substance which, if used separately, would be considered to be a medicinal product and that has action ancillary to that of the device. No ifs and no buts. So no exceptions for devices already CE marked and that already received a positive opinion from a national authority at the time of the original approval under the directive. This requirement is particularly worrisome for manufacturers and, to be honest, for the entire system. It means that every combination device already on the market has to undergo a new lengthy consultation; all of them within a 4-year timeframe.
This would put an enormous pressure on national authorities which, as we all know, have limited (if not very limited) resources, and would very unlikely be able to deal with this amount of work in the available time.
MDCG 2020-12 unfortunately does not change the requirement (and we couldn’t expect that): the consultation is required for all combination devices and the timelines (210 for a full consultation and 60 days for a change) are unchanged. However the MDCG introduces some ifs and some buts giving medicinal product authorities at least some room for manoeuvre. They acknowledge there might be instances where the submission is identical to the original one or with minor differences. In those cases the Notified Body is required (or advised, given the non-binding nature of the document) to provide a declaration confirming which aspects have changed and which aspects are still identical to the original consultation. In these cases, especially when most aspects are unchanged, the competent authorities can decide to reduce depth and extent of their assessment and provide an opinion in less than 210 days. This is entirely at their discretion but the MDCG “highly recommends to expedite the review”.
So everything is left to the goodwill, pragmatism and available resources of the authorities. And although a few things have been clarified, a lot of new questions are arising. Will drug authorities be willing to follow these directions, which are not enshrined in law? If they are willing to follow the guidance and apply it pragmatically, will they be able to handle the large number of consultations required to re-certify all (or most of) the combination devices currently on the market? Will they be able to handle them in the 210 days as required (or possibly faster, as recommended)? And a last important question: what happens if they go beyond the 210 days set for the consultation? At the moment under the directives nothing happens, and consultations dragged for longer than required are not entirely uncommon. It is nice to dream that the new regulation which has stricter requirements for manufacturers and puts higher expectations on Notified Bodies, will also enforce at least the timelines that are black-and-white in the text.
Two more things are worth pointing out in relation to medicinal product consultations. The first is that the MDCG formally encourages (but cannot enforce) collaboration between competent authorities. If the authority involved in the original consultation (MDD/AIMDD) is different form the authority conducting the MDR consultation, the former can be contacted and “at its discretion, confirm the opinion provided in the previous consultation and/or share any additional information”. The second is that once again it is made clear that the concept of liability of the medicinal substance to act upon the body has been removed from the text of the MDR. So any device that incorporates a medicinal substance is class III and subject to consultation, no matter the amount, form or the way it achieves its function.
Very similar is the situation for devices incorporating material of animal origin (TSE susceptible). The requirement, unchanged from the MDD, is for Notified Body to submit a Summary Evaluation Report (SER) to their national competent authority prior to issuing a certificate. The SER summarizes the Notified Body assessment of the risk associated with the animal material. The receiving competent authority operates as a ‘coordinating competent authority’ and shares the SER with the other member states. The competent authorities can provide comments, which typically require to be addressed by the Notified Body (although this is not specifically mentioned in the legislation). This feedback should be provided within 4 weeks, if there is an EDQM certificate for the animal material, and within 12 weeks if no certification is available.
MDCG 2020-12 suggests the same approach outlined for the medicinal product consultations. If a device is CE marked under the directive, was subject to an animal tissue consultation and no or limited changes have been introduced, the competent authorities can decide to shorten the time of the new consultation. At their discretion. In this case this is not entirely new as it was already mentioned in the animal tissue regulation (EU) 722/2012 that reads in article 5(5) that “the competent authorities of the Member States and the Commission may agree on shortening the time periods”.
The situation seems slightly, but just slightly, less problematic than in the case of drug-device combinations. Three reasons for that. First of all, the devices incorporating TSE susceptible animal tissue are likely to be much less in number than those combined with a medicinal product. Which means less consultation and less likelihood of a bottleneck. Then, the timeline for the consultation is relatively short so minor delays should not be excessively disrupting. Finally, the consultation is less demanding for competent authorities. They are not expected to conduct part of the assessment but just to check the results of the Notified Body’s. And the consultation is based on a sort of tacit consent. If a national authority does not submit comments to the coordinating authority within the set timeframe, that equates to a green light for the Notified Body to proceed. Whether the lack of comments means they are satisfied or means they haven’t assessed the SER at all, that is for nobody to know.
In summary this new guidance document provides some reasonable and practical ideas to competent authorities for avoiding bringing the whole system to a halt. However the implementation is left to the goodwill of the member states. It might work or it might not. As they would say in school: A for effort.