EU vs FDA Medical Device Regulation: Convergence or Divergence? (Nelson)



hi everyone and thank you for listening to my podcast today for this project I decided to focus on the EU vs. FDA medical device regulation particularly focusing on whether or not the two regulatory agencies are converging or diverging in the context of this topic I hope to to address whether or not they're converging and diverging and further explore how this convergence or divergence may then affect how sponsors design their international regulatory strategy so to begin let's provide some background on the new EU MDR so in the spring of 2017 so may a pro May of last year the new medical device regulation all was introduced in the EU so the medical device regulation application date is set for a goal of 2020 now there are exceptions to this 2020 rule but but for the purposes of this presentation well except 2020 and given the current changes users under this MGR can continue to use non expired MDD that's medical device directive certificates up to four years after the application date that they currently have and I'll go into this a little bit more in the presentation so to start why did we get to this point what were the causes for these changes that resulted in this new MDR so to first start you know there's a lack of traceability and transparency of medical devices particularly in the EU additionally there are new products coming to the market that didn't quite fit into the current regulatory frameworks and we talked a lot about in class it was not a you know fitting a square peg in a round hole as it were and then further and probably most importantly recent controversy is concerning medical devices in Europe and globally really demand that these agencies address safety better particularly recent cases of metal on metal hip implants and piphus silicone breast implants really shed light on the need for increased safety as a result in an effort to regain trust and really prevent unnecessary risk to the consumers us as patients the EU established a more verbose medical device regulation that ultimately placed safety further at the Forum so discussing changes to the new MDR so the most obvious change is that the document itself is four times longer than the medical device directive that its predecessor also the term safety itself is included in nearly 300 times compared to only 40 times in the previous directive so something to consider here which will unpack more later in this podcast is does the fact that we mentioned safety more actually make devices more safe is the fact that it's four times longer and there's more regulation actually better and safer for consumers some things just have to think about so in regarding specific changes there are a number of key changes to the MTR I have included some of them on this slide and the following slide but please just as a reminder I've selected just some key changes not entirely comprehensive but we'll dive deeper into a few of them that I find most important for this group so it's a start one of the first changes to the MDR is the recertification of existing products within the context of this new regulation so there's no grandfathering provision so devices that were previously grandfathered in as legacy products must be recertified under this new regulation and that might mean quite a bit of work for the majority of companies that might have might operate within this grandfathering put provision a lot of paperwork a lot of administrative work to be done additionally there may be were some requirements to update technical documentation clinical data and label there may be reclassification of select medical devices into higher risk category so this is something to think about right so when a device itself depending on its situation it actually may be considered to be higher risk than originally classified and this new classification of particularly reusable surgical devices now require a notified body oversight continuing on to additional changes to this MDR so you know concerning reprocessing of single-use devices these are processors must ensure safety and performance that are equivalent to the previous single-use device requirements establishing a unique device identification and UDI track the devices through the supply chain there's been an expanded definition of the medical device to include non medical and cosmetic devices this includes the sterilization and disinfection of various devices and in particular so requirements for more in-depth clinical data proportionate to the level of risk associated with a device pre and post-market so I'll dive more into this later but that is one of the big ones additionally there's a centralized UNAMID data portal so touching on that UDI and traceability where all incidents and injuries are reported so substantial illness and death those states have reporting there used to be a 30-day window now there's a 15-day requirement so it's a little bit faster another thing to think about is hey you know 15 days that's about two weeks you know so is that still too long won't discuss that too much here but something to think about and something I thought about through my analysis so performing more of a deep dive into these key factors of the MDR I mentioned that I'll highlight a number of the key factors on the previous slides and then deep dive into a few few more that I think are most relevant excuse me so the first is clinical evidence so one of the most important changes companies may face within the scope of the new MDR concerns clinical evidence within the new MDR the clinical evaluation and Nicolle investigation requirements will expand quite significantly historically sponsors companies were able to base their arguments for equivalents on prior devices in order to eliminate that clinical burden or mitigate that clinical burden most devices will now need some form of clinical evidence regardless of classification type as I mentioned on the previous slide and devices will be expected to have to evaluate clinical data to have a clinical evaluation plan and require a clinical evaluation report concerning high-risk implantable devices or Class three devices they'll require clinical data including actual clinical investigations that are conducted by the sponsor of course all of this in accordance with the good clinical practices deemed necessary so something to keep in mind is well exactly how much clinical evidence is needed is determined by a ranging of factors inclusive of the level of risk or clinical individuation the fact that now you know these devices require a summary of safety and clinical performance reviews it's new and a new requirement for sponsors that they should be aware of and and our action item so something to keep in mind additionally so for the post market clinical surveillance side the MD are really bolsters that clinical surveillance under you know the the new regulation no longer is it going to be just a simple check box that you know we've done our surveillance for nearly all medical devices inclusive of the lower class devices there will be expanded forms of surveillance and you should you should expect that as a sponsor so there will be a mandatory post market clinical follow-up that p.m. CF and periodic safety update reporting requirements that will ensure that the clinical evaluation and risk management is accounted for something to keep in mind is that in this context manufacturers will also be required to identify and address if there are gaps between so the clinical evidence to sure device compliance with current standards so where the device is at now and where it needs to be in terms of being compliant no need to address that gap and of course so expanding transparency traceability via this UDI system it ultimately will make monitoring the whole lifecycle of the device more transparent so it allows patience for manufacturers for healthcare institutions to access the relevant data on these various devices and ultimately hopefully reduces medical errors and makes it more efficient in identifying medical devices so continuing on to the main topic of my presentation is so EU MDR and FDA convergence or divergence so now that we have a background on the EU MDR and we've studied the FDA context quite a bit in these last seven weeks or so given these changes are we seeing a convergence of the two regulatory agencies towards harmonization or are they diverging given this context so I argue that there is rationale to to defend divergence so in terms of you know divergent policies the first fact that I discuss about the MDR is that it's four times longer right there's a physic like actual literal lengthening of the MDR and Wow you know that may be relatively small potatoes in terms of the the debate it is something to consider conversely the u.s. is seeking a trimming of regulatory policy so I 2017 the Trump administration calls for 75 to 80% reduction in in regulatory or regulations that served as burdens and that just too much regulation was burdensome and inhibiting in the context of of health care inhibiting patients from getting access to treatments they needed this is sort of where in which pass we've discussed you know the new expedited 510k and how yes you know that is an additional regulation and new regulation but the goal the ultimate goal was to answer the administration's call for the tightening of regulatory policy and it is a way that the two body regulatory bodies may be diverging more importantly though an example of divergence concerns how sponsors can rationalize predicates so under the new MDR in order to use a similar device as a predicate it must be either with own you're within your own product portfolio include comparatively extensive literature review or be reverse engineered to be deemed comparable and this is what we've been discussing over the past six weeks or so while this may not necessarily be an issue for devices that are already on the market or be you know a major concern for large companies that you know may already own their predicate and they know all the background information it won't be it may be challenging for some startup companies or companies that are maybe less resourced to gain EU approval of via this mechanism because competitors you know as we know aren't willing to or often aren't willing to share technical documentation about their products additionally so in the EU there's an emphasis on direct predicate comparison whereas conversely the FDA has said you know there's limited need to do head-to-head comparisons and more often paper comparisons will suffice so discussing this in the context of impacts on international regulatory strategy so now that we understand hey okay so perhaps there is some divergence in these two regulatory agencies what does that mean for us as regulators what does that mean for us designing our regulatory strategies within companies so while the MDR you know will be fully functioning more or less in 2020 regulatory strategists have already begun assessing what this means for their company's product portfolio people are getting quite nervous and and I would argue maybe unnecessarily so but but it nevertheless it is important to discuss and to have a plan so historically you know when companies have brought devices to market they bring their products to the EU first and this was primarily due to the additional time and clinical requirements needed to enter the US as we discussed earlier some of these changes in the new MDR may make it so that whether we enter the EU or US market first it may not be so clear such a clear-cut decision you know for smaller companies with more limited device portfolios the administrative changes in the MDR may be easy to accommodate there are less employees less bureaucracy to sort of navigate for larger companies with larger portfolios they may face additional challenges and in terms of being able to address you know grandfathering provisions of products within their portfolio or if there are substantial gaps between their device and where the MDR requirements are they might have to address that then the transition may be a little bit more difficult for these larger companies further larger companies that may have acquired device portfolios through mergers or acquisitions they may struggle to adapt to these MDR changes as these changes may highlight maybe technological limitations or or even fragmented interdepartmental processes within their company these are just you know hypothetical but but something to think about that may actually happen within companies and further you know regardless of how large or small the company these changes will make regular to regulators or hopefully make regulators think you know this potentially might change the way my company or our companies engage with global markets so applying your knowledge I thought something that might be useful would be to present case studies of how these various regulatory frameworks particularly MDR and FDA environments impact devices so I've presented three hypothetical case studies that highlight and discuss different classified devices so low res medium risk high risk to be compared against the US and EU systems and the hope is that from this webinar and in the discussion board we'll all be able to provide input on which market to enter first and the various descriptors on the potential regulatory challenges that manufacturers may face through the process so my first case study is a chisel an osteotome so to present the case study so in this first case study you have a startup company GW devices based in the US and has developed a new surgical osteotome or chisel that is a reusable surgical chisel to be used and cutting bone it is not implantable nor life-sustaining so currently in the u.s. right if we were to push this through one of our pathways osteotome or chisels our first classified as class one devices they are 510k exempt exempt from premarket notification requirements and are subject to general controls in the EU due to the low risk associated with this class one device under the regulation vo declaration of Conformity is satisfactory and there's no additional conformity assessment that is required within the new MDR approaches toward class one devices are similar to that in existing in the previous medical device directive and except except that now under the MDR this class device will now require notified body reviews the only difference more or less is that the notified body review is needed which does create a extra work but something to think about further in this context the osteo tone does not fall in the category of devices that are up classified excuse me so when reviewing the international regulatory strategy for this class one device now knowing sort of what we know how do we approach this how do we design an international regulatory strategy or regular to regulatory strategy in general so I present these three questions which a regulatory body do we approach first what are the factors we should consider given this devices classification how is this device affected by the new MDR or is it affected at all so after processing through this a little bit I would argue that a tandem approach towards the US and EU market is an important option to consider instead of focusing solely on entering you know one market versus the other it's important to take a global approach and that might actually be preferable now that notified body review is required for this class of one device in the EU this may extend some time for the review compared to the prior review under the medical device directive and so that said you know given this extended review time that occurs under the MDR are there significant advantages entering the EU versus the US market before that was one of the the major pitfalls is that oh you know the u.s. takes so much longer there's so many more hurdles well given these new medical device regulations in the EU is that the case anymore so something further to consider is you know when startups are seeking seeking funding venture capitalists now also require companies to develop parallel strategies so these parallel in truly global approaches before funding so that might be something to consider when devising your regulatory strategy this class one device doesn't require a regular tour I'm sorry does not require clinical data and the devices risk is extremely low so you know approaching both markets in tandem might eventually just provide you the largest market share so now I'm moving towards a case study to the a laparoscope so in the context of this case study startup company at GW devices based in the US has developed a new reusable laparoscope to be used specifically in surgical specialties so it's not implantable or life-sustaining they in the u.s. laparoscope some classified as class ii devices they're reusable and FDA quotes validated reprocessing instructions and reprocessing validation data for this device is required so from a regulatory perspective and the u.s. we can say okay so can we do a 5-2 in case emission and is it appropriate and how does substantial equivalence tie into this substantial equivalence can be established via a predicate device and paper comparison in the u.s. in the EU this device would be classified as a class 2a and may be considered a short term active invasive invite device so short term meaning you know it's in the body for a short amount of time but it is indeed invasive under the new MDR you know with this class 2a classification GW devices will need clinical head-to-head comparison data that's you know a major difference there and without technical documentation on their predicate the company may need to either you know reverse engineer the comparison or say you know that this device this is not the case but if the device itself was no longer available they would need to reference the literature in order to support that so following that GW devices would need to prepare a technical file which includes actual clinical data this technical file must then be notified or audited rather by the notified body and further as a us-based company GW devices will also need to identify a representative in Europe that represents them to the European regulatory authorities so there are multiple steps they're involved in this pathway so now coming back to these questions so which regulatory body do we approach first what are the factors we should consider given this devices classification how is this device affected by the new MDR is it affected at all and so in processing through these questions while I would say you know a global regulatory strategy like that taking in case study one is always ideal doing so requires a lot of resources and that's not always available particularly for startups so important things to consider when submitting this type of device you know whether it's to the EU or US or a tandem approach is the type of testing required to prove substantial equivalence so if entering both markets at the same time you know isn't possible I would actually advocate for an EU entry market first for this device because in the EU there there are notified bodies right so we've discussed this a bit before in our presentations but in the EU we are able to shop around for notified bodies and have conversations ahead of time with these bodies before actually selecting them as the reviewer so as a regulatory strategist you can essentially shop around and find a notified body that actually will provide you feedback and potentially even be willing to accept it the paper comparison so so that's a that's a benefit you know I would say in comparison to in the FDA we're notified bodies don't exist in the same capacity so or don't exist that said you know entering the EU market first allows you to select your notified body and that you know may be more favorable to your product provide you that feedback and then you can then use that feedback to leverage in your discussions with FDA so my final hypothetical case study concerns a biventricular pacemaker so in this case study startup company GW devices has developed a new biventricular pacemaker with you know some sort of innovative means of stimulating the heart it is both life-sustaining and implantable and currently in the u.s. pacemakers as we know are classified as class three high-risk devices concerning potential pathways to market you know you think okay so PMA de novo what are their options are they're in analyzing what might work so Genova pathway deals with you know down classifications and should be used for devices where you know no predicate exists and whose risk is actually lower so class one or two but I would say you know given the innovative way this device claims to stimulate the heart and level of risk in the US perhaps maybe advocating for submitting a PMA submission is more ideal because of the competitive advantage it has over your competitive companies establishing the new way of stimulating the heart is indeed an innovative and and significant act towards the patient so that's something to consider and then also you know logistically as a small business with no as a start-up with no prior PMA submissions the company would actually qualify to have their first PMA fee wave so these are all just small logistical issues that really do add up in the end and when you're discussed deciding which regulatory agency to engage with first something to consider in the EU under the prior and medical device directive and the new MDR class three devices such as pacemakers would require the design dossier which is the critical step you know for Europe's EE marking process for this type of device under the MDR this device will need more rigorous clinical evidence than than what was previously established GW devices will then need to conduct clinical investigations to ensure they have sufficient clinical evidence to support safety and performance claims so overall you know I what when when addressing the questions I posed on this slide so which regulatory body did we approach first what are the factors we should consider given this devices classification and how is this the fight device affected by the MDR or is it affected at all you know I would I might say that you know ideally a truly international strategy it is is the key with additional clinical evidence requirements in the EU this will ultimately extend the time variation in the EU market that reduces the differences in benefits between the US and EU market so that's something to consider and that said it may benefit GW devices to take this tandem approach it possible you know but if you know resources are scarce and you can't do the tandem approach I might actually advocate for a u.s. first strategy because it holds stricter requirements and as discussed in weeks past a company would not want to necessarily waste resources to redo and to redesign clinical studies that they could have initially done to meet those stricter requirements again because that really just wastes a ton of resources and and so when balancing which regulatory agency our body to to approach first with this high-risk device it's a that is an important factor and further you know we won't touch them too much into this in this discussion but something to think about and perhaps discuss in the discussion board is what is the role of CMS and reimbursement in this narrative so looking forward to discussing that more as well with you folks so the new MDR so what is a truly revolutionary does this actually make devices safer I mean this will be interesting to discuss in our discussion board to see you know yes it's longer yes discuss the safety yes more clinical evidence is required but does that actually mean safer devices for patients and you know all this work on behalf of regulatory staff to update their their portfolios in accordance with these regulations what does that actually mean so I'm looking forward to discussing more of that in the discussion board and overall you know I would just close with we live in an increasingly globalized society where the goal is to reach harmonization and with continuous development of these innovative devices for patients it's so critical that we implement international regulatory strategy from the beginning and so while the MDR will increase clinical data requirements and address device classifications and and increase post market surveillance for companies companies should not be too concerned over these new regulations because a lot of these these regulations already exists in in other regulatory bodies whether that be the US or Health Canada Japan etc so while the additional work may appear to be you know a little burdensome for regulators at this time ultimately many of the regulations are administrative and hopefully if implemented early with a true international strategy from the beginning the current divergence that we're seeing between the EU and MDR will play a significant role in the ways regulatory strategists develop their device lifecycle plans so thank you very much for listening and I'm interested in hearing your thoughts in the discussion board thanks again

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