Breakthrough Device Designation in the EU: A New Regulatory & Market Access Pathway

Man. Hello and welcome, everybody. I'm Sean Smith from MedTech Leading Voice. Welcome to today's session. Our topic is breakthrough device designation in the EU, a new pathway that could reshape how innovative devices reach European patients. I'm going to turn it over to Matthias. To do some introductions in a second. First, I'd like to make a few housekeeping announcements. This webinar will be recorded. And the recording, and slides, I believe, will be available tomorrow. So if you registered, you should get a link sent to you for that. If you would like a certificate of attendance, please put your name and email address both in the chat. We're going to use the chat for communicating with me, we're going to use the Q&A function for communicating

with the speakers, so if you have questions for today's speakers, please, please use the Q&A function, not the chat. I'll be posting a few announcements in the chat, so let's see… Certificates… Alright, and then the last thing is, on the 18th of this month, we're planning a special webinar with Acrateam and a few notified bodies to talk about the pending announcement for MDR and IVDR revision, which is supposedly dropping on the 16th. So that webinar will take place on the 18th, and I'm going to drop the registration link in. Make sure to register for that and share it with your colleagues, because this is going to be another equally important event to this one.

That said, I am done talking, and will gladly turn it over to Matthias.

Yeah, thanks, Sean, and yeah, good morning, good afternoon, good evening, everyone. I don't know whether you're watching us from now. It's really… Clad, great to be here, and we have this webinar, and we have a very wonderful lineup of speakers today, or panelists. We are not going to do a lot of presentations here, we really want to give you, the audience, a chance to interact with the speakers, so… We talk about a very interesting topic, and when we were planning this webinar, the plan on… this was what was announced, okay, the MDCG on breakthrough devices is gonna get published by the end of November. It hasn't been published yet, we're already close to the publication date, so really glad we have done a Connor here.

He's the clinical manager of medical devices at the Irish National Content Authority, and he's one of the co-authors of that MSG document, so even if he cannot share the document yet, because it has not been fully endorsed, he's going to give us an insight on what's in the documentation, so really looking forward to that. We have Dan Korsnit now here, he's, Vice President and Regulatory Affairs of Histosonics. manufacturer in the… based in the US, they received a breakthrough designation by the US FDA, I think 4 years ago. He's going to share a little bit of experience, how the process works in… will work for them in the US, and also in the UK. And also, you have Richard Holborough here, head of individual compliance, for PSI.

one of the largest nullified bodies to get nullified bodies, or BSI's, opinion on that. So, I don't want to spend too much time with the introduction. As Sean said, if you have any questions, please use the Q&A. to put this question in, we have an initial presentation by Donald is going to share, let's say, some insights on the upcoming NCG document, and then after that, we're going to start right into our panel discussion, the focus will be on EU MDR, because, this is what is really gonna challenging, what's gonna change in here. We get this new Breakthrough designation, MDCG. The US already, since, I think, 2015, has the Breakthrough designation program, so they have a little bit more experience.

But we're all very glad that now, finally, Europe also gives manufacturers the opportunity, if they have some breakthrough innovative technology, to maybe have an easier or faster access to the market. We're gonna hear this probably from Donald now, and without any further ado, Donald, please, floor is yours.

Donal O’Connor: Thank you, Matthias. I'm just gonna share my screen now. Donal O’Connor: So, good afternoon, or good morning. Donald O'Connor has introduced me very kindly. I'm the clinical manager in the Irish Agency, but I'm also the co-chair of the Donal O’Connor: MDCG Task Force in the European Union for Breakthrough Devices, and co-chair that with Portugal and the European Commission. So, I'm going to give you a bit of a whistle-stop tour to where we have arrived, Donal O’Connor: come into the very final stages of, getting a new process and a new MDCG guidance,

Donal O’Connor: endorsed and hopefully published while it still is the year 2025, and possibly around the same time as that other announcement on December 16th. Donal O’Connor: But I'm going to take you through the new pathway for breakthrough devices in the EU. Today, we'll go through the essentials of the breakthrough definition or criteria, the designation process, some of the supports that have been put in place to try and assist. Donal O’Connor: innovators in this space, and some clinical evaluation considerations. And from the outset, I will say, when I speak to some of those points, in the interest of time, I'm going to focus a little bit on what's been emphasized for medical devices, and particularly

Donal O’Connor: Higher risk medical devices, but the breakthrough, criteria, the breakthrough designation process and pathway does cater for both medical devices and in vitro diagnostics. Donal O’Connor: So, to take us back to when we started this work in December and into January earlier this year, obviously. Donal O’Connor: From all stakeholders, there was a call that something needed to be, given special consideration in the area of innovation or breakthrough devices. Call from all stakeholders, from industry, to assessment bodies, to regulators, to patient groups, to the political side, that we needed to

Donal O’Connor: do a little bit more to try and promote innovation for various reasons in Europe, obviously. Donal O’Connor: In the interest of keeping industry active, but also, very importantly, to make sure that innovative devices are available for our healthcare professionals, and ultimately, our patients and wider public health interests. Donal O’Connor: So, like many things in Europe, when there's a call, we set up a task force or a working group, and this was no different, so under the framework of the European Commission's MDCG, Donal O’Connor: Medical Device Coordination Group, which is contribution from all member states. We established a task force, and myself representing my own agency, and Portugal,

Donal O’Connor: volunteered to co-chair this work with the European Commission, and with direct involvement from the European Medicines Agency and the Office for the Expert Panels. We had several member states also contribute, and in terms of our drafting groups and various subgroups and consultations. Donal O’Connor: We had a lot of input from our notified bodies, of course, industry, and also independent clinical, academic, scientific community, and indeed. Donal O’Connor: Various patient representative groups. Donal O’Connor: And before I get into any of the details, I want to set out that, really, the mission or mandate was to produce

Donal O’Connor: The first sort of working definition or criteria of a breakthrough device technology for the purpose of CE marking in Europe. Donal O’Connor: Another mission was to establish an independent designation process for that. Donal O’Connor: We also wanted to produce some, but not an exhaustive or overly prescriptive, but some framework for clinical evaluation guidance to give Donal O’Connor: A little bit of a template and structure, Donal O’Connor: to highlight to both the manufacturers and indeed, of course, the assessment bodies and notified bodies to try and improve some predictability and make it a little bit more feasible to bring breakthrough devices to the market, and also to introduce some supports, which I'll speak to, and predominantly that in the first iteration of this new process, will be

Donal O’Connor: and priority access to centralized scientific advice via the EMA's expert panels. Donal O’Connor: So, without further ado, probably the highlight of this presentation is, the announcement of what are probably the final stable version of what will be the breakthrough device criteria for Europe. Donal O’Connor: And forgive me if a comma or an and or an or changes between now and the publication in a couple of weeks, but this is essentially what the material aspects are. So a breakthrough device Donal O’Connor: Be it a medical device or an in vitro diagnostic, will be defined if it meets the following criteria.

Donal O’Connor: And the first aspect is novelty. Donal O’Connor: And that is a device that introduces a high degree of novelty with respect to either the device technology itself. Donal O’Connor: Or the related clinical procedure that it facilitates, or the application of that device in clinical practice. Donal O’Connor: And the AND is very important, because all of this is about producing devices that are useful for clinicians helping their patients, so the positive clinical impact is the second criterion. And that's where the device is expected to produce a significant Donal O’Connor: positive clinical impact on patients or public health for a life-threatening or irreversibly debilitating disease or condition in either of the following scenarios, where it offers a significant clinical impact

Donal O’Connor: Compared to the available alternatives and state of the art, or in the scenario where it fulfills an unmet need, so where there is an absence or insufficiency of available alternative options, be that other devices. Donal O’Connor: Medical products, or even other therapies or other treatments for that purpose. Donal O’Connor: Now. Donal O’Connor: Also, what we're soon to publish is a little bit of a framework to assist manufacturers in setting out how they meet that criteria, and that's broken down into the novelty aspect and the positive clinical impact. So, in terms of novelty.

Donal O’Connor: On this slide here, it's not the exhaustive list, but it's a few of the examples that will be published in the guidance. So, in terms of the device technology itself. Donal O’Connor: Novelty could be due to the materials themselves in terms of their physical composition, their biocompatibility features, or changes in the release of characteristics of substances which may have efficacy or safety characteristics. It could be novelty in respect to the design, how it incorporates other technologies. Donal O’Connor: For example, new biomarkers, new platforms for biomarker testing, how it integrates with other devices.

Donal O’Connor: It could be novel to be with respect to the type or the sample or specimen that can be now used. So, for example, a blood test were only previously, Donal O’Connor: Other tissue biopsies were available. Donal O’Connor: It could be something that's more convenient and easier for the patient in terms of how it facilitates extension of the technology, so near-patient tests compared to something that maybe historically could only be formed in hospitals. Donal O’Connor: In terms of the clinical application, that's an important aspect of this, so… and that was particularly of concern when we did consultation work around in vitro diagnostics, where there was a concern.

Donal O’Connor: only a brand new breakthrough technology in one sense, or first in class could meet the criteria. But existing technology can still meet the criteria for novelty if it's shown to be used in a way that's not Donal O’Connor: not heretofore been used in clinical practice. So, for example, an in vitro diagnostic that detects or measures a biomarker for a new or different clinical condition that wasn't applied to before. It could be the mode of application. Donal O’Connor: and in terms of medical devices, so therapeutic medical devices, it could be existing technology, but applied in a way that allows a procedure that wasn't previously possible. So, an easy example there is it allows for minimally invasive surgery versus

Donal O’Connor: more conventional open or maximally invasive surgery, or it allows for other minimally invasive techniques. Or it could be a device that allows for Donal O’Connor: detection or treatment at a much earlier stage of a disease, which obviously could be argued to have an important potential impact on patients. Novelty could also be with respect to the interaction it has with patients or users, including how it's used, or the dependence on the user, be it the healthcare professional or the patient user themselves. Donal O’Connor: In terms of the significant positive clinical impact on either individual patient or public health, there are a range of considerations that will be published in terms of… on an individual patient basis, or the wider public health, but these are scenarios rather than distinct disease or device examples.

Donal O’Connor: that will be included in the guidance, again, to give a little bit of a template to set out how the new device would meet this criteria. So, for example, a device that's intended to either treat or prevent or diagnose a life-threatening or irreversibly debilitating disease. Donal O’Connor: That has a reasonable expectation that it will produce clinically significant improvements in patient-relevant clinical outcomes. Donal O’Connor: And again, they can't be overly defined or prescribed in the guidance, and that's why, as I'll allude to now in a moment, why there has to be a matter of an assessment there with the expert panels in terms of the designation procedure.

Donal O’Connor: Another example would be a device that's intended to treat or prevent a severe side effect that's associated with the treatment of a serious condition. Donal O’Connor: And of course, it's recognized that a breakthrough device could be very important, not only because it provides an efficacy advantage, but because it may provide a safety advantage, so that it allows treatment of a life-threatening or Donal O’Connor: irreversibly debilitating condition, but it has a significantly lower risk of adverse events. And that adverse event term is broader than any of the MDR or IVDR terminology around adverse events or serious incidents.

Donal O’Connor: An example there would be a device that allows for a less morbid procedure, so again, a transcatheter procedure compared to maybe an open-heart surgery procedure. Donal O’Connor: Also, an example would be an in vitro diagnostic, and that could include the companion diagnostics that could provide information at an earlier stage of a disease, which could lead to a clinically significant improvement of the treatment of that disease. Donal O’Connor: So… Donal O’Connor: I'll spend a moment going through some of the considerations that are included and highlighted within the guidance around the clinical evaluation and the clinical evidence requirement considerations.

Donal O’Connor: And I'll say, I'm going to set out the next couple of slides. It's really the emphasis on the higher-risk medical devices, but the principles can apply to all devices or in vitro diagnostics. So… Donal O’Connor: I think it's important to set out that while we hope this new pathway will result in devices making it to market in a more efficient and more predictable process, the intent is not to reduce requirements Donal O’Connor: or to reduce the quality of clinical data that's expected. But it's addressing the true and authentic concept that if you have novelty, if you have breakthrough technology.

Donal O’Connor: There can be, for various reasons, more uncertainty. Donal O’Connor: But that alone is not a reason to delay the availability disproportionately for patients. Therefore, we have to accept that there should be a balance of how much pre-market clinical data is needed to give certain assurances Donal O’Connor: And how much post-market data can continue to be collected to confirm the safety and efficacy and to reduce that uncertainty. Now, of course. Donal O’Connor: We're not saying that, by default, you can just accept uncertainty because of novelty. There still would need to be, as a general principle, sufficient data so that at the time of market access, you can demonstrate the benefit risk is acceptable, and that is reasonably expected. The device will provide a clinical benefit. And that takes into account

Donal O’Connor: The severity of the clinical condition, the state of the art, the presence of alternatives, and various aspects related to safety. Donal O’Connor: It's also important, and we give emphasis on… Donal O’Connor: I think we've probably repeated it several times throughout the guidance, that it's really important to have an appropriate and accurate and well-designed PMS system, and in particular, PMCF, or equivalent PMPF, Donal O’Connor: activities. It's also important, where relevance, and this won't be the case for all devices, that you adequately inform the users, be that the professional users or the patient users, by providing

Donal O’Connor: appropriate information, be that in the IFU, or if it… Donal O’Connor: Applicable in the summary of safety and clinical performance. Donal O’Connor: And if applicable, and again, this won't be the default, that you have appropriate measures in place if particular conditions of the certification have been set, for example, around milestones for PMCF data collection. Donal O’Connor: So I'll just spend a moment on some clinical investigation considerations that we worked through with the task force, and some of this will be in the final guidance that's published, and again. Donal O’Connor: Unapologetically, some of the emphasis is on the higher-risk breakthrough medical devices, because that's where there's a higher burden of pre-market clinical evidence generation. So we have some suggestions and considerations, some principles around study design.

Donal O’Connor: And it's important there that the context of whether it's a clinical impact because it's meeting an unmet need, or whether it's Donal O’Connor: expected to have advantages over alternatives, and that will influence what might be the most appropriate study design. If it's meeting an unmet need, more simple study designs, pre-market may be acceptable, potentially with comparators of historical controls. Donal O’Connor: If it's a breakthrough technology, entering a field where there might be quite an established state-of-the-art, quite an established, Donal O’Connor: clinical, standard of care, there may be several alternatives, well, then the bar is probably slightly higher, and potentially comparative pre-market studies may be more appropriate. We've some…

Donal O’Connor: Highlighted points around the objective of the studies, in particular where it may be appropriate for breakthrough technology to focus on safety, and maybe short- or medium-term performance, and indeed. Donal O’Connor: Without getting prescriptive or into detail about it, some acknowledgement of the concept that surrogate endpoints, if duly validated and followed up appropriately in post-market with clinical endpoints. Donal O’Connor: may be… may be an acceptable way of setting out your study design pre-market. And it's important that the choice of comparator is duly justified in all cases.

Donal O’Connor: In terms of post-market surveillance, and in particular, post-market clinical follow-up dedicated activities, we have elaborated a little bit of this in the guidance, and I think the important take-on point is that Donal O’Connor: It's not generic PMS activities that we want to see. Donal O’Connor: If we're going to accept a higher degree of uncertainty and, for example, a pre-market clinical investigation with slightly more limited follow-up time, I think it's important that there's a highly structured and milestone-based PMCF plan, in that case, setting out just some general principles, the type of data that will be generated proactively.

Donal O’Connor: And how it will address and ultimately sort of reduce that pre-market uncertainty in terms of Donal O’Connor: Continuing to show data on safety and longer-term performance. Donal O’Connor: And we've highlighted some examples of PMCF activities. They could be clinical investigations with longer-term follow-up. Donal O’Connor: Could be use of registries, or other sources of real-world evidence, and other activities. Donal O’Connor: And again, I don't want… Donal O’Connor: A simple message here being that CE marking with conditions under certificate is going to be a default of this adapted pathway. That's not the expectation, but this could be a good example where, in establishing

Donal O’Connor: the agreement for CE marking that certain milestones of the PMCF activities, when they're addressing certain aspects around the safety and performance of the device, they could be set out as specific conditions of the certification to be met. Donal O’Connor: In the months and couple of years that might follow CE marking. Donal O’Connor: And I haven't put up a slide for the interest of time, but we do have a section around the non-clinical or pre-clinical aspects. Again, it's mostly focused on the higher-risk medical devices, but calling out the importance of Donal O’Connor: well-conducted preclinical and non-clinical work. Again, when there's novelty, there's going to be a little bit of extra elaboration potentially expected there to try and, again, reduce that uncertainty and rationalize the pre-market clinical evidence generated.

Donal O’Connor: So briefly, I just wanted to outline a little bit of the expected role of the EMA expert panels. Donal O’Connor: So, the principal role, which we hope will start soon if the pilot is launched in early 2026, will be the independent designation process. So, a manufacturer who wants to request a breakthrough status for their device will request this. Donal O’Connor: by requesting scientific advice for an opinion on that status from the EMA, and that will be following that assessment, and we expect that this will be a 60-day timeline that would be forwarded then for recording to the European Commission.

Donal O’Connor: I think an important thing to go complementary to all of this, apart from just producing a criteria definition, and some high-level guidance, is to try and assist the manufacturers Donal O’Connor: from SME all the way to the major multinationals, with early scientific advice and examples there, and this would be from the appropriate thematic panel in the therapeutic area, and that would be arranged with the EMA to provide advice on the manufacturer's clinical development strategy, for example. Donal O’Connor: Clinical investigation design, and indeed the post-market clinical follow-up activities as well.

Donal O’Connor: A feature that's also been called out and highlighted, and is possible under the framework in Europe, is that the expert panels could be requested by the relevant notified body to provide opinions on the sufficiency of the clinical evidence during the conformity assessment procedure. So not to extend the procedure, but to be done in parallel. Donal O’Connor: And then the role of the Commission, the MDCG members, including agencies like my own and the EMA governance procedures, is to oversee this and roll out a pilot in the next couple of years and ensure that both the criteria and the procedure for providing scientific advice are all fit for purpose.

Donal O’Connor: So, I'm going to finish now, because I'm sure there'll be lots of discussion on that, and I hope that snapshot and initial, Donal O’Connor: outlining of the… maybe the principles and the intent of this, breakthrough criteria and designation process, and indeed adapted pathway, will be of some assistance and interest to you all, so thank you very much. I'm gonna stop sharing now so we can, not be distracted during our panel discussion.

Thanks, Donald. Great presentation. Really, thank you that you provided us so much insights into that, and .

Donal O’Connor: Yeah, and Kate's already got a lot of questions coming through, and .

Yeah, just a reminder, everyone, please use only the Q&A window to put in the questions, because this is the one we're going to monitor. So one quick question, Donald, just through your presentation, because it, it looks like that the manufacturer, and this is a little bit different to the orphan device designation, so you have to go through the expert panels. It's a mandatory step, so they cannot just apply to a nullified body, and then make a nullified body doesn't make the designation. It's basically a mandatory step before the application nullified body. that you need to get this application to, the expert panel, and they have to define the breakthrough designation status, and then later on, after that, you can apply. Or can this be done in parallel, saying, okay, to a manufacturer save on time, you mentioned 60 days. Can the manufacturer submit to a notified body, and in parallel submit to the expert panel for the designation?

Donal O’Connor: No, that's a very good point to address, and I do want to make sure our audience are clear on that. Yes, that is a little bit different from the pathway that's been established for morphine devices, so… Donal O’Connor: In orphan devices in Europe, it is very much voluntary if the manufacturer wishes to maybe reaffirm their decision that they consider themselves to be an orphan device with the expert panels before going to their notified body. Donal O’Connor: And it was felt there. There is some objectivity there, because there's an epidemiological aspect there in terms of the expected numbers.

Donal O’Connor: To be, to be treated or diagnosed with the device. And indeed, in that pilot, and maybe Richard might speak to that later on, I… I think we do have some, some, some, Donal O’Connor: I suppose, good data there that it's… it's… it has been constructed in a way that is really reasonably reliable there, and that the notified bodies, even in structured dialogue, and I'll oversimplify that there, have been able to make use of the guidance to agree with the manufacturers. Donal O’Connor: And because of… there's quite an objective part of the criterion then, I mean, it's quite credible and defendable.

Donal O’Connor: Here, because there isn't that… it… all of… all of the criteria really are a little bit of a matter of assessment, and the manufacturer has to set out their case. It was always felt that there should be an independent designation of that. Donal O’Connor: And, now, to the point of whether you would get the designation first. Donal O’Connor: Or could you go in parallel? Well, you could apply for a designation opinion from the expert panels, and independent of the timing that you approach your notified body. Donal O’Connor: However. Donal O’Connor: I think, realistically, if… for the notified body to have a chance to take the breakthrough designation into consideration, and I suppose to apply the guidance, it may make more sense for it to be in the…

Donal O’Connor: to be sequential there, but there's no… there's no absolute rule. I mean, in terms of when you go, and it is set up in a way that Donal O’Connor: A manufacturer will be able to apply for designation, really, at any stage in their development, from very early stages to more mature stages. In one sense. Donal O’Connor: To take advantage of all the various offerings, it maybe is of most advantage to a manufacturer in a very earlier stage of the development, because even through the expert panels, there may be an opportunity to even seek some feedback on some of the aspects and preclinical development.

Donal O’Connor: And the expert panels in the EMA would call in additional resources to assist with that. Donal O’Connor: and to get that scientific advice, even be, you know, before they maybe start their structured dialogue pathway with the notified body, and then I suppose all actors can take advantage of it. Donal O’Connor: And what I didn't mention is there could be other advantages to breakthrough, and we might elaborate on this further, and I'm not sure if it'll come up in the questions, to breakthrough status that go beyond the predictability or the efficiencies or speed of CE marking in terms of it may get recognized for other purposes that are

Donal O’Connor: Beyond the mandate of the initial publication of the guidance, but we would hope this will be taken into account by, for example, funding bodies and all the way up to various reimbursement Donal O’Connor: processes in Europe.

Okay, thanks. Dan, your company, you already went through breakthrough designation status in the US, and also through the IDEA program, in the UK. Can you quickly walk us through, did you see any benefit, or how was the process? Just quickly, to give us an experience that your company had recently with getting breakthrough designation status?

Sure, Matthias, thanks. Dan Kosetna, VP of Regulatory Affairs for Histasonics, and we did receive breakthrough designation for our device. In the U.S. in 2021, our device is, uses, focused ultrasound to non-invasively destroy and liquefy targeted liver tumors in a very precise, predictable way. It's a mechanical mechanism of action. There are various novel Aspects of it that, you know, made us confident that… that we'd go through the… and be successful through the breakthrough process. And we were, but the timing of our… application, we are… we already had an approved IDE and things like that, and so the,

the benefit to us of having breakthrough status was, hard to… to quantify in terms of, like, speed through the process and things like that, because we didn't have as much engagement with the agency. after we had breakthrough designation, and that's one of the benefits, or purported benefits of that status. In the UK, we were in the pilot for the IDAP program and the unmet clinical need, and they were working through their processes, It was a fairly substantial interaction with that group, but it did ultimately lead to an unmet clinical need designation, and we were able to place product in the UK market very recently, which is ahead of our CE mark.

status, or design, our CMARC status, so that… there is a tangible benefit through the UK, but I will say, and maybe this isn't your question, Batias, it's not an insignificant effort to engage in these processes, and so having a good understanding of why you're doing it and what benefit you're seeking is important for companies as they decide Whether to, to put forth the effort to seek the designation.

Great, thank you. So… and just a quick follow-up question. Do you… do you… I mean, you don't have that much other experience, so do you think it was a faster process at the end, or do you think, as you said, it is a lot of effort, yeah? Or would you say it's comparable to, let's say, a regular 510K or 510K submission?

Well, it's less information in the breakthrough designation, in the U.S. The… IDAP program was a pretty similar lift to compiling a full 510K. In terms of the benefit, in the U.S, you know, as an example, you talked, Donald talked about other potential benefits besides, you know, speed to market or predictability. And one of the reasons we decided to seek breakthrough designation, was a proposal to, marry a CMS reimbursement benefit in the U.S, I think it was called the CMIT proposal, that would have meaningful reimbursement benefit for breakthrough designated devices. And that was a motivation for us, and that never passed in the law. I think recently a modified version of that did pass in the law. And so, again, understand why you are getting it. Was it faster? It's hard to know, because we didn't do a parallel path without breakthrough designation, but…

I know there's been around 1,100 FDA devices that have achieved breakthrough designation per their database or their publicly available information, but only 160 have gone on to actually get market access through either a 510K PMA or de novo, so, it's hard to draw a conclusion, positive conclusion about improved speed through those statistics.

Great, thanks for the insight. Richard, I mean, we just heard from Donald that the expert panels will be handling, or will be basically, a mandatory step for the designation of a breakthrough device. We heard that they can provide some early in the process, like, even the design and development phase. some feedback. So, Richard, from a notified body perspective, we saw that notified bodies are going to get involved too, but probably not before the start of the conformity assessment application. Where do you see, the role of a nautical body at this point, and what support, I mean, you cannot consult, of course, but what support, maybe in the structured dialogue.

Can the notified body provide the manufacturers who want to go through the Brexit designation program?

Yeah, no, I think one of the things that you'll often hear me say in public is the fact that we need to bring… if we want predictability to bring innovation to Europe, we need to make sure that the decision makers are involved as early as possible. And the decision makers in this system are the notified bodies, that's what manufacturers want. I think what the expert panels offer is slightly different to what the notified bodies offer. The expert panels are very much offering scientific advice, around maybe the clinical trial design, etc. Now, whilst notified bodies will have clinical expertise within their institutions to support such discussions.

What the expert panels lack that the notify body can offer is that regulatory insight, the knowledge of conformity assessment procedures, what's expected, etc. But I think it's fair to say that, you know, even through structured dialogue, you know, we can have conversations with manufacturers in support, so once a manufacturer is even thinking about applying to the Expert Palace of Breakthrough device pathway, it would be good to notify your notified body that you've chosen to have those conversations, to let them know you're approaching. we probably would say that the, as notified bodies, you know, there's often this question of, oh, or this statement that notified bodies cannot consult, and that's true under Annex 7, Section 1.2.3 of the MDR, it's quite clear that notified bodies cannot consult.

But Team MB is working, you know, with and making some proposals with the Commission. We know that the longer-term, inputs into the regulation will cover structured dialogue. And I think what we see as notified bodies is that structured dialogue is different to consulting. Structured dialogue is about when a notified body is able to provide commentary on a manufacturer's methodology, and consulting is actually when a notified body is providing the methodology to the manufacturer. I think that's where we've got to get our mindset into in terms of this process to work. So, Matthias, to answer your question, I think, you know, we will, you know, as notified bodies, we will obviously be looking at this very carefully.

We understand there are also some longer-term measures that might pick up things like, you know, as notified bodies, we might need to publicize our timelines in terms of how we are approaching these pathways. We've been told by the European Commission that, you know, we need to be cost-sensitive to these devices. They are a public health need, so we need to make sure that where there is something being developed by industry, that notified bodies need to support that, and we are open to that. we can have conversations of structured dialogue with manufacturers, you know, pre-application and post-application, and the MDCG guidance talks about that. There's certain things we can talk about post-application, and there are certain things we can talk about pre-application, and one of those things is to make sure that, or one of the reasons behind that is to make sure we don't end up in a notified body shopping point, or shopping world, which

we know that humans will take the path of least resistance. So, what Don was saying about having this objectivity with the expert panels, I think, is really helpful. It also supports us as a notified body, if you go to the expert panels and you get that breakthrough designation. That allows me or my team in the notified body to say, okay, well, we can… we can make provisions on the preclinical data and have limited clinical evidence, but make sure that we've got conditions on certificates. So when the authorities come in and question us as notified bodies on the decisions we've made, we've got the support and the

I guess the labelling of something being a breakthrough device by the European expert powers, which gives us the confidence to move forward, but also gives the authorities the confidence that notified bodies are making the right decisions for the right devices.

Great, and I think it's very important that you highlight that we really also know if our bodies these days have this tool of structured dialogue to really get into, let's say, earlier discussion with the manufacturer. provide some regulatory feedback that probably the expert panel are not able to do, so I think this is very good that, now we have, let's say, these two pillars now, the expert panels and also the notified body structure dialogue that manufacturers can get in very early contact. I see a couple of questions coming through, basically looking at, okay, we have already, or what is with the device that already got breakthrough device designation in the OS?

like Dan was just telling us, is this gonna help? I mean, I fully assume it's not automatically translated into a designation process, practice designation in Europe, even if the definition In the MDG is very similar to what the… how the FD80 defines a Brexit device, but, maybe, Donald and or Rich, what's your opinion? If… if a manufacturer, like Histasonics, for example, already have Brexit designation. in the US. Does this somehow help in the European process, or is there still a possibility that even if the US considers a breakthrough device, it's not going to be considered a breakthrough designation in Europe?

Donal O’Connor: Well, I can probably start, Donal O’Connor: I, I, well, I think, officially, there isn't a… Donal O’Connor: automatic mutual recognition, but I don't want that to be overly negative. I think it would be quite… Donal O’Connor: Realistic that it would certainly help, because… Donal O’Connor: the same type of information that would have been provided for the FDA's process. I mean, we didn't write it completely siloed to the FDA's process. You know, we've had informal discussions over the past couple of years with Donal O’Connor: people who were involved, even all the way back, I think, more than 10 years ago, with Andy Farb, who really led the FDA's,

Donal O’Connor: Breakthrough pathway, and we obviously, Donal O’Connor: Because of the decentralized system, we can't completely replicate it, but in terms of the principles around device technology, advantages over alternatives, it is quite similar, so… Donal O’Connor: I would hope that a device achieving designation via the FDA, while they will have to go through the process and request it officially in Europe, it's a very similar burden, maybe, of documentation, so I don't think they would… Donal O’Connor: have to, start from scratch or anything like that. And actually, that would be a thing I'd be keen that, I suppose, the responsibility of the competent authorities and the Commission who have

Donal O’Connor: drafted this and created this process, that we'd appraise that, and certainly we, you know, we would be open to… Donal O’Connor: revising the criteria, because it would not be the expectation that devices that meet the FDA's criteria would not pass the examination in the European system. That's not the intent at all. I think they're reasonably complementary to each other, and I would hope they would, Donal O’Connor: they would achieve it in Europe as well, and that's important. Now, there's different thresholds, obviously, in terms of actually the market access and various things, things like that.

Donal O’Connor: I'll just pick up one comment from Richard. I think it's important. I think, yes, the expert panels in their current makeup will have certain expertise around study design. That will add Donal O’Connor: You know, credibility, because hopefully they'll be agreeing and giving advice, and either disagreeing or backing up manufacturers on their proposals around, sort of, authentically and generating data that will assist Donal O’Connor: The notified bodies agreeing that that's sufficient clinical data. Donal O’Connor: But I do think the input from the notified bodies, really, who ultimately are, you know, are taking on the assessment there, is really important for the predictability, and I think that's what any…

Donal O’Connor: emphasis, and for many of the regulators, maximizing that, and if certain things need to change in the MDO revision to make that even more possible, we're certainly not against that. Early advice is really important. Donal O’Connor: It can be done in, you know, a very appropriate way that isn't consultation, but it really assists in good quality data, but that's predictable and useful being generated. And in the pilot. Donal O’Connor: And I think we've mentioned this at the stakeholder session at MDCG recently, we will explore even getting that expertise. In Europe, really, like, clinical evaluation… evaluation expertise obviously is at the notified bodies, it's not really at the competent authorities. Certain expertise is obviously at the expert panels.

Donal O’Connor: To incorporate that, potentially, not into the designation process, but into the scientific advice process, be it either meetings with the expert panels, and potentially exploring how that expertise can be brought in. Donal O’Connor: To, improve the predictability of that scientific advice.

Yeah.

Add quickly, Matthias, sorry, Richard, you're going on a different topic, but I just wanted to say, after seeing Donald's presentation, you know, from an industry perspective. if you have either achieved breakthrough designation, or if you've completed an application, you can leverage a lot of the information you put together in that FDA submission for an EU submission. There's some important nuanced differences, and I think I like the language of what I've seen there in terms of a significant clinical benefit versus the FDA language is more effective, which we kind of tied ourselves in knots in a little bit as we were going through our process, but, I don't think the lift should be that high on the application, but again, I stress

Make sure you're willing to do all the work if you get the, status, because there is a fair bit of engagement, involved, so…

Yeah, if I may add, you know, I think Dan won't mind me saying this, but, you know, Dan, you are currently in application with us at BSI for your device, and, you know, even before this guidance, you know, you came to… you came knocking on the door of BSI, and you had conversations with us about this being a breakthrough technology, and I was very privileged to come and visit your facility and see what I think is equivalent to a James Bond movie style. It was fantastic. of what you're doing. But I think that that's really important, is that, you know, if you have the FDA breakthrough device pathway, well, that's great. You know, use that as evidence when you're having those conversations with your notified body as well, about, you know, why this is an unmet medical need. These reasons that you've achieved that status will still be applicable in Europe, because the healthcare systems are very similar. So often the options that exist between the two healthcare systems

Are… are very, are very similar, but… I think… you know, what, again, what we can offer, and you know, those early conversations with Dan as part of structured dialogue involved with, you know, what would we consider as sufficient clinical evidence in this situation, but also, what is going to happen in the post-market phase? You know, we as notified bodies wanted to have that security and that confidence to know that, you know, those products are going to be rolled out sensibly, they're going to be installed in centres, for example, and that, you know, we look at things like conditional certification. So, making sure that people are trained appropriately, that you're reporting back to the notified bodies on a frequent basis of your post-market clinical follow-up. So again, this control and patient safety remains at the heart of us releasing this innovative technology in Europe.

Richard, I prefer Star Trek to James Bond, but I get.

Okay. Star Trek, I would go with.

I, I like, I like that, yeah. Donald, quick question to you, because, there was one question from the panel saying, okay, well, Similar to, to, to Hesothonics. they already have Brexit designation in the US, and they were asking, saying, as a question, is there, like, say, a pilot program or something, accelerated program, that these companies who already have Brexit designation in the US like, a pilot program that gap the designation in Europe. So, like, once the MDCG… I assume once the MDCG is published, the program will go live, or does it take? It's going to take some time until manufacturers can apply for the Brexit designation in Europe.

Donal O’Connor: Thanks, Bates. Yeah, I don't have the exact timings. We're hoping to publish this, let's say, while it is still the year 2025, so we've got a couple of weeks left. Donal O’Connor: Our colleagues in the EMA are not just waiting silently for it to be published. We've been working in parallel with them, so we would hope that the pilot for accepting applications for designation would be able to launch soon. You know, soon might be Donal O’Connor: you know, a couple of months into 2026. And then the specifics of exactly how you apply and the procedure will be outlined by the EMA there.

Donal O’Connor: it's hard to predict how many applications there might be. We've done some exercises looking at how many designations Donal O’Connor: you know, are performed by… in the FDA, and I'll do a note that Dan made a very pertinent point. The number of designations Donal O’Connor: is, almost logarithmically higher than the number of actual final PMA decisions. It's sort of a thousands, and then maybe one hundredths. Donal O’Connor: But I think, really, if someone already has breakthrough status and has their paperwork ready that was… that achieved that, they, they could be in a position to submit very soon in 2026.

Donal O’Connor: The designation process itself, I don't have all the specifics of it, is not intended to be overly burdensome. It should be a reasonably refined procedure. Again, an important consideration here is that to achieve designation that's very different than sufficient clinical evidence for CE marking. Donal O’Connor: very little or potentially no clinical data may be available to the manufacturer. You know, in terms of the way the criteria is set out. Donal O’Connor: Proof of principle data, preclinical data, reference to their devices, state-of-the-art, various ways could meet Donal O’Connor: enough evidence to justify that you meet the criteria. So, some manufacturers at a very early stage in development actually could apply for designation if they wish. Also, manufacturers, of course, who are… have already undergone PMA in the FDA would obviously be able to submit immediately.

Donal O’Connor: If there's a lot of applications, or if there's predicted to be a lot of applications, I can say from discussion with the EMA, which is probably reasonable, there may be a priority criteria almost within the pilot. Donal O’Connor: Where they may accept, applications, based on the risk, class of the device. Donal O’Connor: And it's Europe, so we do have to pay attention to general European Union healthcare priorities and, you know, so therapeutic areas like oncology, pediatrics, cardiovascular diseases are all very high on that agenda, so… Donal O’Connor: You know, they may feature as priority criteria. But essentially, it's not restricted to device class, but that might come into account in terms of prioritization for accepting applications.

And so, Richard, from a multi-part quality perspective, let's say it's going to get published let's say December 15th, yeah, and the manufacturer's gonna, I don't know, forcing the designation, but let's say they're going to contact you, let's say, in January, are the notified bodies ready already? at this point, to implement the process. I mean, it's still the same performance assessment procedure. It's not gonna… it's not an abbreviated version, but it probably, I think, similar to what we see with the Orphan device and ECG. It might allow for a limited quality and quantity of clinical data, so…

how the modified bodies are preparing for that? Did you have, let's say, your own department within BSI who's gonna handling that, or is this just gonna be part of the normal standard process for other devices, and does it affect, let's say, your regular work on the 95 body? Might it slow down other reviews, because there will be a prioritization of these innovative devices?

Yeah, I think, I think it's fair to say, I think you make a good point. You know, we still have to go through the conformity assessment process. There are no cuts in any, you know, shortcuts or loopholes that we can jump through in order to avoid those things. We have to go through those. I think, you know, I can't speak for every notified body, but certainly, you know, I know that in discussions across the notified bodies as part of Team MB and NBCG Med, you know, we will continue to support this process. To speak specifically about BSI, you know, we will, or we are waiting for the guidance to be officially released.

We will then implement the MDCG guidance into our processes at BSI in terms of making sure that we do prioritize these applications. I don't think we're going to see huge numbers in terms of that would impact in any way, shape, or form our standard conformity assessment activities for those that are progressing through MDR. But we will continue to support these devices, and we have history of doing that even without this guidance of making sure that, you know, unmet medical need gets prioritization. Some of the things that, you know, have been told to notify bodies as a group is, you know, again, you need to give these priority. They're a public health, you know, concern, you know, if there's an unmet medical need.

So, the other thing as well, of course, is the costs of the notified body, and we need to be sensitive to those. So we are hearing that some notified bodies may be offering what they have, often a dedicated service, for example. They may offer that, but at the standard price. So again, there's differences that might be able to support the process of those. I think, you know, we are talking about a very, very small part of what is a big ecosystem in terms of supporting startups. You know, I can see some questions coming through about, you know, reimbursement and the health technology assessment, and there's developments being made there.

I think in Europe, there's a lot more work that needs to be done in terms of helping startups that sit outside of the notified body. You know, MedTech Europe were, you know, reporting that 7% of overall conformity… sorry, overall costs to meet the MDR were just notified body costs, 7%. But we know, for a small-medium manufacturer, that 7% is probably likely to be higher. There are, legislative requirements already that exist that require that notified bodies do take into account the considerations of small, medium enterprises in terms of their prices and other factors as well. So, we are working on it. I think, you know, let's not forget this guidance will be released on December the 16th. It will be a… or hoping to. We'll be,

working very hard in the background into the new year to make sure, I think all the notified bodies will look at this and think about how we can implement that. Conversations with the Commission in terms of longer term, is that, you know, if notified bodies are taking these applications and working, you know, effectively on them, then, you know, they should be… those notified bodies should be prioritized to receiving those applications. You know, if we've got a notified body that's got a 24 month timeline in order to get a conformity assessment completed or set up, then there's an issue in the system. So we need to make sure that if notified bodies are performing well.

to these devices, that they get priority to help the bigger public health market. So, there are some very interesting conversations happening behind the scenes that I think will ultimately lead to a I would say a faster pathway for these devices in the, in the MDR with notified bodies.

Thank you, and a quick question from the audience that I find very interesting, maybe quick answer, maybe Richard, or maybe even Donald. If there's a Brexit resignation. by the expert panel. Is this legally binding, or can BSI basically disagree if their clinical expert says, I disagree with the designation process?

Donal O’Connor: I'll give you my take.

click on it, but you go first, Donald.

Donal O’Connor: Okay, well, if… yeah. Donal O’Connor: No, I definitely need your take on it as well. No, officially, it's… at the moment, the legal basis for the designation is under the current framework, so it's actually… Donal O’Connor: It's really an elaboration on what's allowed under the articles for scientific advice in the MDR. Donal O’Connor: One of them is specific for the higher-risk devices, the Class III and implantable, but then we also have Article 106, which allows for a slightly more broader. So, it's officially a scientific advice and an opinion, so not legally binding. Now, it will be sort of formally notified to the Commission when each opinion is given.

Donal O’Connor: the first use of that is really so we can just record them and sort of appraise them during the pilot. Now, the usefulness to the notified body may be objecting to the designation, I suppose maybe Rich could elaborate on that, because remember, the designation is the designation. It doesn't set out any further mandate around Donal O’Connor: the actual clinical data that's going to need to be produced, it obviously is to be taken into account, because it's important context if a manufacturer is going to justify Donal O’Connor: a clinical investigation with a short-term follow-up, for example, or surrogate endpoints, as an example.

Donal O’Connor: So I think that's… that is an important distinction, because at the designation, it's an opinion. Does it meet the criteria? It's separate from any opinion on the sufficiency of the data that will… that will be… that will be, ultimately, produced for CE marking. Donal O’Connor: But I'm interested to hear what Richard says about a difference in opinion on that.

No, absolutely, Don. I think I agree with you, you know, it falls under the framework. It's not, you know, it's not legally binding that notified bodies at the moment need to prioritize or deal with these, you know, consider these applications, but if you… you know, we will consider them as a conformity assessment under the current legal framework, but I think if we have a situation with a expert panel saying that they think this is a breakthrough device, and the notified body says no, well, what does that really actually change? It's probably not much, because you still would apply to the notified body.

The bigger issue would be if the expert panel said they didn't… they thought it was a medical device, and the notified body said, we don't think it's a medical… those would be bigger issues to deal with, but hopefully we won't find ourselves in that. But I think, ultimately, it doesn't really change anything, because you would still have to apply to a notified body, you would still have to undergo the conformity assessment. You know, it doesn't give you any… bells or whistles legally, but what we should, you know, what the guidance is trying to tell notified bodies is to make sure you prioritize these applications, which, again, that's discussion, but again, you know, if… choose your notified body wisely, I think is perhaps a… perhaps a follow-up comment as well.

I think this is always a very good advice to always choose your body wisely. I think we can keep this. I really have to apologize, there's so many questions and so many great questions, we could only address a few of them. Interesting question at this point, so, maybe, Dan, maybe you can give us some feedback, on what is… what is Historonics approach, let's say, going into Europe? Do you think this is something you could use also, because we already got price resignation, that this entity might be helpful? For you, and then maybe a quick follow-up question to, maybe more to Richard and Donald at the end. What would you say to manufacturers who are currently in the conformity assessment process for 95Wall? You all know this can take a year, two years, depending on the risk of the virus and some follow-up questions.

would you recommend the manufacturer to basically switch at this point, or would you say, okay, it's faster if they just continue with the current conformity assessment, and do not consider this as an additional, let's say, probably maybe a step to speed up that. So maybe then, maybe quickly you can talk a little bit, okay, what is your plan at Europe right now?

Sure, I think because we're under review and fairly, hopefully, far through that… far away through that process, it wouldn't make sense for us to… for our current liver indication to, to seek this designation in Europe, but our technology is going to be, we think, clinically beneficial across a lot of different applications, and so for future applications. it may be in other organs, such as pancreas and whatnot. It may be something that we pursue. Again, I… just really quickly, if I can editorialize, I applaud Europe for moving this way. I think it's important. I think it… I hope it helps. make innovative devices, available there more quickly, because I think that's been a problem under MDR.

I'm hopeful, but somewhat skeptical of accelerated pathways and breakthrough pathways actually making a kind of a measurable difference in how fast things go to market, but I'm hopeful that this one will be an exception.

Great. So, Rich, Donald, would you say a manufacturer is in the process right now, let's say, first round of conformity assessment questions. from BSI, would you say, okay, it makes sense to… if we had the program already, does it make sense to switch? Would it speed up the review, or do you think it's still, because it's the same platform, the assessment process, not going to really get the faster market access?

I think it's something…

mocking.

If somebody's in that position right now, then I would say have a conversation with your notified body under structured dialogue. What does that look like? Because how far are they into the assessment? What's needed to get that through? You know, I think I would say continue with the assessment as planned, and just, you know, again, further evidence to the notified body that, you know, this is serving an unmet medical need, for example, or relate the criteria, so they can take the appropriate actions to make sure that internally they can, where they can, expedite things to try and help get that product to market to help patients.

Sooner.

Donal O’Connor: Yeah, I think so, because in that case, it's likely they've already conducted their clinical… their pivotal clinical investigation, so they maybe benefit a little bit less. If there's other benefits, not yet to be fully outlined that come with breakthrough status, they may still wish to avail that opinion from the expert panel, so… Donal O’Connor: But yeah, no, I wouldn't suggest restarting.

Okay, thanks. I see Jean coming in, that means we have to come on the end, unfortunately. It was a great discussion. I think we had really interesting questions from the audience, very good answers here, and really, hopefully, we now have a pathway forward to make sure that, also manufacturers get their innovative devices. fast and safe to the European market, And also, I just would like to remind everyone, we have another upcoming webinar on December 18th. We're all waiting, we are expecting to see some updates coming to the MDR and IBDR by the end of the year, and this webinar will provide you some insights on that, and yeah, with that, thank you everyone, especially our panelists.

For a wonderful session here. Thank you.

Thank you, everyone.

Thank you, everyone, for your time. Thank you. Bye-bye.