EU & UK - What's My Route to Market? Class I to Class III | LSI Europe '22


Camilla Fleetcroft

Camilla Fleetcroft

VP Clinical & Regulatory Affairs, ECLEVAR
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Florence Longueville

Florence Longueville

Head of Clinical Operation, ECELVAR
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Edmund White

Edmund White

Global Chief Commercial Officer, ECLEVAR
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A critical analysis of the routes to market for the EU and UK, and the requirements around clinical evaluation. Discussion about Notified or Approved body input and critical post market considerations. This session is vital for anyone looking to build an understanding of they key principles and requirements, smoothing the regulatory path, and avoiding pitfalls along the way.


Edmund White  0:05  

Good afternoon. I hope you enjoyed your lunch. So what we want to do with the panel today is to give you a solid understanding of the key principles and requirements to help you in your journey to navigate the regulatory pathway. Our panel will be providing a critical analysis of the routes to market for the EU and UK. We will also discuss about notified bodies and also look at some of the potential considerations for medical device. So first, let me introduce you to our panel. So after nearly a decade of working in the healthcare sector, she moved to the MHRA working within the metal division for over eight years. In her first role as Deputy Director for innovative devices. She led the development of future UK regulations for medical devices following Brexit, and worked with cross government policymakers interacting regularly with ministers and decision makers. Prior to that, she was head of clinical investigations and Evaluation at MHRA, she represented the MHRA at the EU level for clinical investigation and evaluation. And she's also led the implementation of the EU MDR and IVDR for clinical investigations and evaluation in UK. A warm welcome to Dr. Camilla Fleetcroft. So she has nearly 25 years experience leading international teams driving global and international clinical research programs. She posts graduated and medical device regulatory affairs and her spirits in post market clinical activities within the medical device industry such as Terumo aortic, she supports medical device manufacturers and challenges the application of MDR and a very warm welcome to Dr. Florence Longville. So let's get started. So first of all, we're going to just talk about some of the considerations for classifications. So Camilla, how do you define classifications today.


Camilla Fleetcroft  1:52  

So it's very similar to how it was under the directives. And it's really the first critical step. So what we have is annex eight of the MDR. And what you see there is the classification rules based on the intended use classification characteristics and inherent risks of the device. There are still the four main categories that we know and love. Class One is your low risk up to class three is your higher risk. Again, we have the subdivisions, you've got your class to be implantables. Again, not not unfamiliar, class one sterile measuring functions, and now reusable surgical instruments as well. Like I said, you'll find the classification rules in Annex eight, we now have 22 rules, so a bit of an increase with the new regulation. And these are split into four quite distinct sections, you've got your non invasive devices, which are rules one to four, you have your invasive medical devices, which are rules five to eight, your active medical devices again, rules nine to 13. And finally, your special rules 14 to 22. I won't go through all the special rules, but some of the things they cover are if a device has an integrated products that when alone would be considered a medicinal product. Those use for contraception and preventing the transmission of sexually transmitted diseases. Those used for disinfecting cleaning, sterilizing medical devices, those recording diagnostic images for X ray radiation nanoparticles also make an appearance as do devices using human or animal tissue drift generators.


Edmund White  3:32  

Excellent Camila, so what does that really mean Florence in terms of conformity to MDR? How does this all kind of translate and apply to the classifications here


Florence Longueville  3:40  

As to the rules to support the classification of of medical device are set on very specific criteria and and those those criteria are used to classify the the medical device but to just also to to provide this?


Edmund White  4:16  

Yeah, yeah. So, so no problem. I'm gonna just quickly ask a question to the audience. How many of you are developing a class III today? Up there, okay. Okay. And so, Class II A or Class II B okay. So, yeah, so, a mixture here. 


Camilla Fleetcroft  4:35  

Anyone not sure?


Florence Longueville  4:38  

Yes. So, the classification is find in all the MDRC and and direct the essential requirements, so safety and performance requirements. Also, you address the process that you can choose for the notified body evaluation of you have the conformity to the MDR but also you the document that you have to supply it for for the notified body. So, the classification is very is a very key topic and this find through all the MDR to to evaluate your your medical device saying I would like to focus on to maybe on the notified body process. So, the higher your medical device is at risk, and the most, the more the evaluation from notified body will be detailed and accurate. For example, for Class I there is a new notified body involved in the evaluation series an auto self certification from the manufacturer, but he needs to provide to the notified body access of the documentation at least from the Annex 123 of the MDR. And then for the class three, the impact is very huge on the classification, because for class to be implantable, and plus free and plantable devices. For a complete and accurate evaluation is done all the technical documentation that you have to provide. And, and it's done device by device. So there is no way like for Class II A device to have a sampling review of your technical documentation. It's it's a review for the Class III bi type. And, and it is very, it is why it is so important. And we insist and we really recommend that the first tip is when you develop and you start with your prototype is really to have a clear understanding of the class of your device.


Edmund White  7:17  

Great. And so Camilla over to you, what do you think would be the key market considerations for for manufacturers today to get their product to market.


Camilla Fleetcroft  7:26  

So once you have your classification, and you've decided what that conformity assessment route might look like, you do have a few considerations in the process. We know regulation is a bit of a hurdle jumping exercise. So hopefully this list gives you an idea of some of the key activities you're going to need to do. So as you can see, you've already done classification, you've picked your routes. The next thing is our quality management systems. Think about it early on developing your technical documentation, your clinical evaluation that will be part of that responsible persons really important post market activities. And also don't forget things like your UDI and your traceability for your product. So I was just going to


Edmund White  8:13  

Yeah, just a quick quick question here thinking about quality management process in the medical device stage should should not be considered pre market at at a very early stage or foot when should that QMS be considered for a manufacturer.


Camilla Fleetcroft  8:25  

So if you click on to the next slide, I think it's really important to understand that QMS is the underpinning of your processes, and it can add real benefit to your company. If done well, I would say as early as you can think about it. We've got it here in that whole lifecycle from concept through to post market, it will really add value. 1345 is obviously the well known standard. And I never think it's too early to review it understand the principles, particularly if you're going to have to go through certification to that particular standard.


Edmund White  8:59  

Good, good. And going through the sort of the postmarket. Consider the lifecycle piece of this. What do you see is the PMCF requirements and what exactly they review. So we're looking at sort of the the life pole lifecycle here in the post market site.


Camilla Fleetcroft  9:13  

Yeah, so what's what's interesting and different slightly about the MDR is the real focus on explaining and detailing clinical evaluation and post market surveillance and post market clinical follow up. You've got a slide here that shows you the different sections of technical documentation and in Section six around your verification and validation. That's where you find the documentation around your clinical evaluation report and those PMCF activities. It's vital that you understand your clinical development plan where you're going, what you want to do. This document is about demonstrating you meet not only the general safety and performance requirements that you've identified, you should also document the ones that don't apply and why And this is where you want to be building that really strong, scientifically robust data set that says my device is safe it performs and does what it's intended to do, and provides those clinical benefits. It's an ongoing process. I'm sure you've all heard that endlessly. This is not a one and done approach. This is not one document that stops at market access. This is a document that you update you feed in data through that post market work, whether it be PMS, or pm CF. And you continue to build that picture, learn about your product, learn whether the benefit risk ratio is still acceptable, identify any unknown risks, any new contraindications you might have missed, or indeed, off label use, we know, historically, and currently, clinicians often will use devices not quite in line with their intended use and instructions for use. And it can help identify that it really builds that real world picture of how your device is used, and and what it's doing in the real world.


Edmund White  11:01  

Great. Great. So as far as just moving on to clinical investigations here, what sort of evidence do manufacturers need to collect for their device? And where does this begin the lifecycle of the device, so perhaps you can just share a little bit about about that.


Florence Longueville  11:16  

Okay, see, for the what kind of ingredients, I would say it's evidence to prove and to support the allegation from the manufacturer, regarding the intended purpose of the device. So in terms of performance, clinical benefits, clinical safety, and, and, and patient clinical benefits. So it's, it's the data that have to be collected through clinical investigation. So a clinical investigation is a process involving at least one human subject using the medical medical device. So this mean that it can be done and performed through the complete lifecycle of, of your medical device. Of course, the first step is to plan your clinical investigation during the clinical development, they're at the very early stage of your clinical development. Not probably with the prototype, but as soon as you have collected zoom preliminary results, in vitro or in preclinical data on animal and you go in first in human you through clinical investigation. So, the Clinical Investigation are covered in in a specific chapter in in the MDR, and deeply reviewed with the annex for 15 Sorry, and they are several categories to the categories of for the if it is to demonstrate the conformity and then get your device CE mark, or if it is, after the CE mark so has a continuous process, you have to know that the classification of your medical device is also you driving the investigation and your clinical development plan. Because the clinical investigations are mandatory for class three device. Unless you meet some very specific condition, you are allowed to not perform such clinical investigation for class free, but you have really to pay particular attention. So it's very specific conditions. It's for certain legacy device or similar devices are a graded version of your device. But really pay attention because the justification must be very accurate and detail over otherwise, your clinical evaluation will be rejected by the notified body. So I would say on a general point of view, clinical investigation, there are lots of things to do in clinical investigation. You also have to to know that during the design of the clinical investigation might be different regarding this tape, if it's a pivotal a pilot's court or registry. And it's but clinical investigation, it is it is k for the clinical evaluation. And we have the so called other study that are covered by the article 82 of the medical of the MDR. And those study are observational without any additional procedures or no burdensome procedures of your patient. So this means basically it is really observational and registry. So


Edmund White  15:41  

Yeah, yeah, no, that's excellent. Now, there's been a lot of talk about the end of ECG and the guidance documents for MDR. Yeah. So what some of it's quite controversial, let's say, but what would you say is the role of of these documents forgot, as a guidance document for your medical device development? How does how does this play out


Florence Longueville  15:59  

so the MDCG, this medical device Coordinating Group is has different role and the role that they can, that they have to support manufacture, but not only manufacture on this report also notified body, it's to deliver guidance, working work instructions, templates, in order to have a better understanding and a concrete understanding of what is expected we've from the stakeholders of medical device to transition to the MDR, but also you to apply the MDR within within your company. So the library is a huge source of information. In addition to that, the MDC G with the European Commission's does designed and put in place an expert panel, and this expert panel role is very important, it is clinicians with the last update approach clinical approach scientific approach in a specific field. So, they have been categorized in per their field of expertise. And they can be they can participate to, to the conformity or or to support manufacture and the end gating the CE mark at several level. The first level is that manufacturer of class three or class to be medical device can request the expert formal advice prior the clinical collecting clinical evidence. So this is just asking for an opinion. Could you help me my strategy? What should I focus on? I am I on the right way. Do I understand the requirements. And and then the experts panel, provide an opinion provide an advices this should be of course documented in a domain. So this is the tracking record of all of all your device. 


Edmund White  18:44  

I just wanted to fit in there a little bit. It's a little bit controversial. I've heard some of these decisions these panels are making last few weeks in terms of the level of scrutiny for the device what what what can you share about that? Because 


Florence Longueville  18:55  

I know it's so it is not on the opinion that the manufacturer can request prior the clinical development of the device. The controversy comes from the the parallel evaluation of this expert panel during during the request for conformity so the question of of CE mark and see did the notify the BD perform the evaluation provide the report and they expect Palmer provide its report sometime they are different opinion. You knew the first reports from expert panel was issued in July 2021. To date six has been issued so it's not has much to do When you look at the reports, I would say that the notified body are really focused on the clinical evaluation for the conformity to MDR. And the CE. When, but when you look at the conclusion of the expert panel, they have a very high level of expertise and opinion regarding your clinician point of view of your of your clinical evaluation. So for example, they recommend to manufacturer to have more long term follow up to I would say, it's not has much controversy, I would say it's it's rather different points of view regarding clinical innovation and, and recommendation and have more details. 


Edmund White  20:52  

So just talking with the manufacturers today. I mean, there is some challenge to get a notified body in the first place the resourcing challenge, you know, and I've talked to many people, and they still can't find a notified body, you know, for the company. So the MDCG is recent providers, some new guidance around around sort of SMEs and how they can work with notified, what can you just share a bit of light on on that and help


Florence Longueville  21:16  

them? Yeah. So MDCG provides a position paper, several position papers, but they are not the only one. You need, the competent authority for medical devices did the same. Also, some professional association like the PSNI team in France, or the busy made in Germany, or the team in B as well, they are all warning about the ECU that notified body are currently facing the number of the modified body has drastically decreased with the MDR application. So from more than 50, decrease to less than 20 We currently have 32. So that's that's good. But this mean that the restores to get the conformity is not here, I mean, it is it is complicated. And, and, and the notified body moves also to phase two, lack of preparation of manufacture. So what I would advise to manufacture is really to be properly support with your CE mark. Request, it is it is very important. So there are probably many things to do on the manufacturer point of view. Also you on not a notified body point of view. So to get resources to train resources. And, and probably at European level for those legacy device, which are the critical point. Because we are waiting, I would say, hundreds of 1000s, Hundreds of 1000s certificate to be released for the legacy device within the next 18 months. So that's that. 


Edmund White  23:28  

yeah. So just kind of go into that topic quickly. Before we move on to the final topic. What is the crunch point here because, you know, we got may 2024. There's, you know, deadline for recertification. What is actually happening today to to try and alleviate that because we're heading for a bit of a


Florence Longueville  23:43  

Curiously, I would say every day, some legacy device, I will not allude anymore to you to be on the European market because they lose their MDD certification. And they and they don't have the MDR certification. So recently, the Medtech published a team NB article, I think it was from the director of the TMB and her say it is very well, it very well is to illustrate the situation because this lady she claims for a generic transition and certification of of legacy device for one year. And, and this is I would say a general warning and request for her from professional association.


Edmund White  24:42  

Yeah, so the warnings are out there. So we've got a few more moments. Just want to kind of get Camilla now to touch on the UK here at the Brexit. what's the implication for the manufacturers here in terms of how to adjust to the Brexit and the specifics of the situation here with a device today?


Camilla Fleetcroft  24:58  

Of course I think everyone knows it's a difficult and slightly complex situation. So, for the UK in terms of regulation is broken down into Great Britain, which is Scotland, Wales and England, and of course Northern Ireland. Under the rules for Great Britain, the UK MDR 2002 has remained on the directives level that was already transposed into UK law. But because of the Northern Ireland protocol following the exit from the EU, they have automatically taken onboard the EU MDR and IVDR. And indeed, they are already in force. And the UK government has made legislative changes to make that happen. So I won't go through it but you've got two clear routes at the moment either you get your CE mark, or you get a UKCA mark to be on the UK market both fine until July 2023. Not a lot of time until then, at which point in theory, you will need a UKCA mark to be on the Great Britain market. Those of you who are interested in the UK regulations will know that the MHRA published a very extensive public consultation in September last year and it closed in November. They responded in June this year. And we see a lot of alignment with the EU. That's hard to avoid, but also some differences where they're looking to really strive forward and make a regulation that is more agile, it's more robust. And indeed it looks to be very globally leading. There are some key key topics that I think are of real interest in that said domestic assurance routes, which looks to whether there could be an abbreviated assessment by notified bodies for recognized jurisdictions. And whilst the MHRA do not specify those jurisdictions, the general thought is that would be like the likes of FDA, maybe Health Canada, and of course the EU. We await further drafts of the legislation, we've only got the response so far. But like I say, as far as we're aware, the July date next year still stands. But thankfully, the MHRA in their response set out that there will be a transition for people on the Great Britain market. And there are three categories of that anyone who has a UKCA mark before the implementation of the new regulations can stay on the market, either until their certificate expires or for three years. Those who have a CE mark under the directives equally they have to be on the market before the regs come into force, which of course they would be, and they have until their certificate expires, or three years, whichever is sooner. And the final category is really interesting. And actually I think adds the most value is that those who CE Mark under the EU MDR can be placed on the market anytime in this transition period. And they don't have to be on before the new UK regs come into force. And they have up to five years or until their certificate expires. Again, whichever is soonest so there is a bit of breathing room,


Edmund White  27:57  

I'm gonna ask you a question. If I'm a manufacturer today, would it make sense just to come to the UK first, go through the process here and then go to Europe because there's some period there transition?


Camilla Fleetcroft  28:08  

I mean, it really depends on your regulatory strategy and where you want to be. But certainly at the moment, the UK regulations are based on the directives. So for those that perhaps would have a lower classification under that they might deem it pragmatic to get that mark, enjoy the transition period. But I think it's it's really difficult because we heard this morning, people think it's extra cost for quite a small market. But like I said, I think it's it's about the bigger picture, what can the UK offer in terms of development, the life sciences sector is really strong. And I think the UK is an exciting place to start and to sort of invest in moving forward, but I completely appreciate what an awful lot of people have said to me this morning, is that there's a lot of unknown. We'd like I said, we do not have draft legislation yet. So the exact details are not there yet.


Edmund White  28:59  

Yeah. Yeah. Great. And then Florence sort of wrapping up a little bit here. How's this all gonna kind of plan out to the future here, how do you see this planning?


Florence Longueville  29:10  

How does say the planning, see, I mean, the transition is coming to an end to as a manufacture you have now it's not anymore, be ready or be prepared you have to act and and really to to ensure that the your transition period is complete, you are compliant to to the MDR internally you you have in place the your quality management system you know, if you you have to know if your device class has been upgraded based on the on the MDR and then you go have additional record arguments for for your, your medical device and proceed for clinical investigation. Tomorrow we have a session regarding the reimbursements. In the maybe I can just introduce that session in France, the reimbursement required medical based evidence, medical based evidence comes from clinical investigations to if you can anticipate for you see Mark, for you conformity to MDR for legacy device not reimbursed in France, those medicine, medical based evidence and get the reimbursed. That that's very, very good ID and not wait for the well, how our session, we'll discuss that role, but clinical data and Clinical Investigation of very important.


Edmund White  31:05  

Yeah, good points there. So yeah, so let's, let's kind of wrap up a little bit here. So maybe we can just kind of summarize really, the topics we went through here today on the route to market, you know, we've gone through quite a bit here of content for the audience. So maybe start with you, Camilla. Maybe we just want to kind of summarize some of the points here key points to look out for as a manufacturer today.


Camilla Fleetcroft  31:28  

I think critically, it's been methodical classification is like we said, a very critical first step, understanding what you have in your hands and what your device does, and what risk classification is really directs and dictates that journey that you're going to go through. We've seen that it takes how you performed assessment will happen, but equally the extent of data required, the way you get that data is really important. And I think it's for me, it's really important to remember that we always talk about a nice cyclical lifecycle of devices. But that's not a smooth process, you will find that your journey is not just a lovely circle with arrows pointing from one box to another, there are lots of interdependencies. So you will jump backwards and forwards from various sections and processes. Again, that is why a good QMS is really important. And just being very, I guess controlled and understanding exactly what you as the manufacturer needs to do for your products. There is not one size fits all, this is about you learning and directing the journey for you and your product.


Edmund White  32:37  

Great. That's great. And Florence any final remarks from you?


Florence Longueville  32:41  

I would say that the this MDR application can be and can be seen as very complex and complicated process. Actually it is. But some companies are here to support you. So we are at ECLEVAR, we have a strong board of experts, we have regulatory experts, we have clinical trial experts that can provide you support to develop your clinical strategy, flew the compliance to MDR. review with you the clinical evidence that you have got clinical data that you have already connected and tells you advise you are those these clinical data or evidence regarding the safety, the performance, the clinical benefits, is it what is required for the MDR so don't stay alone. Have and request support from professionals.


Edmund White  34:02  

Great. Thanks for that lovely sum up Florence. And so let's just wrap up so that big thank you to everybody here. Thank you to the organizers, LSI Scott and team. Thank you to you, Florence, Camiller and thank you audience so hope you enjoy the rest of the afternoon and have a good meeting. Thank you very much



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