Clinical Evaluation Pathways for CE Marking w/Steffen Ruschinski

Hi! You're muted! Can't hear you.

Yeah. Now you can hear me.

Yeah.

Hope, so, yeah.

How are you?

I'm fine. I'm fine curious how it will be today, but everything is fine on my side. I hope you, too.

Oh, yeah, everything's good. Just promoting.

Hello! Hello! Everybody!

Yeah. Hello.

How are you?

Yes, oh me! Yes, I'm very fine.

Nice to hear.

Sonic here in Basel, are you in not least in the States.

Yeah, I'm located in Germany. So I think.

In Germany.

And a lot of participants will be in the States here. But I am in the middle of Germany, so not so far away from Basel.

No, no, no, no, absolutely very near. Yes.

Yes.

So while I'm busy promoting everybody, I want to play a new game. The best thing that you ate this week, and the worst thing that you ate this week. So if you just go ahead and put that in the chat, or anybody that just feels like blurting out their answer, the favorite thing that they ate this week, and the probably least healthy thing. I don't know sounds like a fun game, because there are a lot of people. So I'm just sitting here hitting the promote button, trying to figure out a new way to do this so that everybody gets in automatically. But it's been no.

If you can repeat, please again the from the week, the most worst or and the most happy.

Food, something that was yeah, something that you ate that was really good, and something that you ate.

Okay.

Hey? You're you're ashamed that you ate. For example, I had chocolate, chocolate chip cookies for breakfast today. Not not very proud of that.

I can imagine.

We call it Italian breakfast.

I have eat the orange pie portocarlopita, which was super. Yeah. And it it start to be more popular also in Germany, in Switzerland. You can buy it by little, for example. something worse I cannot now remember. Yeah, sometimes you can buy fruits which are not anymore good. They are injected with wax, and maybe from Valencia, or from Greece, or whatever, and they are not really from from the apple, from the current apple, and the you buy it. And after a while in the replicator, you see, it starts to to be really bad. Yeah.

Yikes.

Well, I harvested some black currant and made a pie out of it, together with my wife. So yeah.

Okay.

From the bush, you know. That's No, no buying, no storage just fresh as it comes from the bush.

That sounds delicious.

Yeah, it is.

Yeah. Just joined from Taiwan. Hi Michelle.

How's the food in Taiwan?

Michelle.

She's muted.

I am muted there.

It. It's the food here is amazing. People here are amazing. So every time I come I just like. Oh, I ate too much, but they say, Oh, just eat more because you're going home next week.

In China they have something they call. I enjoyed this one.

What is like a dampling.

Something. Yeah, that's.

My favorite restaurant.

Yeah, you dip it in in the soy sauce and eat it with chopsticks. So it's really enjoyable. When I was in Beijing.

I never been to China. I'm sorry

Yeah, well, there's certain political. There's certain political tensions that I know. And yeah.

Let's hope it doesn't get any more intense as it is. So let's see, did did anybody write in the chat what their favorite food was this week. Let's see reading some Taiwan Luke had strawberries eaten directly from the plant in the garden. Best food this week. Apricots worst food this week. Beef Burgers love beef burgers, oxtail stew, yum lemon cake, another good one. anyway. I'll let you guys read the chat while I continue. We have 50 participants. This is a record.

Wait to see? Yeah.

If you would like to be promoted to Panelist, and I have not promoted you to panelist. Please raise your hand because I'm having trouble keeping track of who's declined and who is wanting to be promoted and plus people keep joining so I'm a little distracted at the moment I need a helper. You should deputize somebody. Carrie, for example. And

I think Carrie has the whole deputy energy about her. Does she.

Yeah. Let's see.

Yeah.

I think I think I think she might like take over if I did that.

Yeah, you gotta be careful.

More like boss energy than than deputy.

Oh!

And just just fun, and with.

We'll we'll definitely spice things up here, I think. Yeah, I'm voting for Carrie. It's gonna be called the lead.

That's how much coffee I've had right.

Lean and carry campaign.

Okay. While while I'm doing this, I'd like to introduce today's speaker, Stefan. He is going to be talking to us about clinical evaluation pathways to Ce marking. And I'm gonna let him tell us what he means by that. And then do you have a presentation for us, or is it? Is it? What? How are we doing it?

Yes, of course I have a presentation for you. Let me just share my screen. and you can tell me if you see, can see this so so.

So so before you start, I want to hear about Stefan as a small child dreaming about being a regulatory affairs, professional as an adult. What did you dream of being 1st before that dream came to you?

Oh, God, it's so long time ago. Definitely, very, very unusual. But as my 1st job I became mathematically.

Okay.

I always wanted to be a scientist, but at 1st it was math books.

Map.

Yes, Smith.

Oh, okay.

Very unusual, but it is like this.

Any other math fanatics in the audience.

Picked my career path because it doesn't require math. I'm the opposite, but I really respect mathematicians.

Yeah. But I think we all need it just also for- for everything. We need all these statistics, too. Yeah, this is very, very nice also for me that when you can see this and you understand this, what is written there? Of course.

Yeah.

You need, you know, do we need more? Is it okay? Is it sufficient, or whatever? So I think it's also a big advantage in this area that I'm now in for more than 20 years.

Until.

I'm a math, Major.

Yeah.

Engineering physics and advanced mathematics with a biomedical engineering intent.

Oh, great to see. Yeah.

I was a math elite.

Yeah, not not me. And mine was painting, drawing, and sculpture. So.

Until I got out of stats. I didn't want to take statistics.

Yeah, okay, let's go ahead and get started, Stefan. We're ready.

So just just once again, you all see this presentation. Now, yeah, I think so. Yeah. Okay. So also from my side, a very warm welcome to all participants. glad to see all these people here. So and just, we'll just start just before starting. That's what the completeness this presentation is based on my best knowledge, of course, and of my understanding of the requirements that are now in line for the medical devices in Europe. Very shortly about me. I am 1st time mathematican, but also I am in the medical device sector now, since more than 20 years, or almost 20 years. mostly as medical writer for clinical evaluation Reports, Pms. Pmcf. For medical devices.

where I have already now evaluated more than 150 devices. My main indications are cardiology. I've done a lot also in Ecmo and in osteocentesis. I'm also startup judge for a big innovator. I am the Advisory Board for some startups. and I'm also investing myself in startups that are promising and interesting for me, Cherry, shortly about me today I want to.

Before you go forward. Where are you calling in from? Where do you live and work out of.

I live in Germany just in the middle of Germany. I have to say big big cities, I suppose, Paul, maybe you know Cologne, and you know, Frankfurt are mine, and when you just put a line between these 2 cities just in the middle, there.

So you're there now.

What?

You're there now you work.

I am in Germany now. Yes.

Okay. Fantastic. Just curious. Good.

Yeah, of course. Yeah. So I 1st want to say, want to do the grounding today? Here, I want to show you what are the biggest pitfalls in Cpc. How can we avoid them? What are the top nonconformities for the notified body responses before we go to the different pathways that lead to cemarking wet device legacy devices. Article 61 orphan devices. Cmt devices. We will go through this later in detail, and for all these, what is sufficient clinical data if we have a little bit time, and then I don't know yet how it's going, and if there are a lot of questions in between. I don't know. Then we will have a short look at the new Mdcg. 2025, 6 for clinical evaluation of Mdais, which was just released last week.

So 1st of all, what's the aim of a clinical evaluation? We have to prove the compliance with the relevant Gsprs. In accordance with Annex, one of the Mdr. We have to assess adverse effects. We have the assessment of the benefits with risk ratio, and very important. We have to verify medical or clinical claims of the manufacturer. Before we can write a clean evaluation report, we have to plan this report. And what are the requirements and what are the contents of the Cep. we have to determine the relevant Gsprs.

We have to set the intended purpose of the product, including indications and contraindications. We have to describe the critical benefits. product specifications and instructions for use. You have to include the risk management results already preclinical studies. For example, biocomparability. We have to include a clinical development plan for this special product and our data. Pms and Pmcf, so Victoria already has a question I saw, oh.

No, Sean had put a comment.

Okay.

Anyone who wants to be promoted to panelists, but not yet, thanks.

Okay? No. Problem.

Okay, thank you so much.

Yeah. And 1st for the Cep, what we have to do 1st is that we have to determine our relevant Gsprs requiring clinical data that are not well. Our pitfall for these Gsprs is that these Gsprs require clinical data, and this data is not identified or incomplete and or do not align with those identified in other parts of the technical documentation. For example. the sufficient accuracy, precision, and stability of a device with a measuring function is supported by clinical evidence from a clinical study. But we don't mention the Gspr. 15, one in the Cep. So manufacturer always has to ensure that all references to the Gsprs. Which require supporting clinical data are aligned across. The whole. Technical limitation

in practical is, according to the Mdr. Article 61, one. We need at least the Gsprs. One and 8. There are still exceptions where we don't need them after Article 61, 10. But in practice we can always recommend also to use the Gsprs. 5 and 6, meaning mistakes by user. For example, if you have risky products that are used by non-professionals like blood measure, blood sugar measuring, and Gspr. 6 is the safety and performance throughout the whole lifetime. For example, if you have implants in the body of a patient that are not intended to be taken away after some time, then this lifetime still has to be the same as the remaining lifetime of the product.

If you maybe will submit the technical documentation to BSI. I can only recommend that you. the Gsprs. 5 and 6 inside them, otherwise it will be refused.

Can you make your slides a little bigger? Is that possible? Is it possible to maximize them.

I, you know, have had to do this now.

Oh, sorry!

No, no, sorry I have no idea how to do this in my screen, because I just using different screens it is as big as as possible. Here.

Okay. Well, maybe you can make the slides available afterwards.

Yeah, of course, of course, yeah, no problem of this. So the second pitfall is that the intended purpose is vague or is incomplete. And the documentation does not clearly differentiate between the intended purpose and the indications. As we need a clear, unambiguous, and specific intended purpose which fulfills the article 2 12 of Mdr. Intended purpose critical for determining that the device is a medical device, and further, the device's risk, classification and clinical data requirements. It is subject to scrutiny by the notified body, and will be challenged if vague or incomplete.

So our clinical evaluation plan should clearly differentiate between the indications and the intended purpose so, but in the absence of an Mdr. Definition, manufacturers are directed to the Mdcg. 2026, where the indications defined as the clinical condition that is to be diagnosed. prevented, monitored, treated, elevated, compensated for, replaced. modified, or controlled by the medical device. This should be distinguished from the intended purpose or intended use which should describe the effect of the device.

lack of consistency in the intended purpose, and indications for use across the devices. Technical documentation is our next pitfall, which is very often named by the notified body. So manufacturers are advised to cross check the intended purpose, statement, and indications for use throughout the whole technical documentation. the clinical benefit. So this is the role of the device in improving the health of the patient or patient management or public health is not clearly described. Accurately defining the clinical benefit is an important starting point in the clinical evaluation process, as the Mdr. Requires the manufacturer to demonstrate that the benefits associated with use of the device outweigh the potential risks to patient safety.

When defining these clinical benefits, the manufacturer should consider the role of the device in diagnosis, monitoring, prevention, treatment, elevation. etc, of a device, injury or disability and the subsequent positive impact. If we have software devices role of the software in the overall clinical workflow should be carefully considered dependent on the clinical performance of the device. The clinical benefit may be direct or indirect. Very, very crucial point is now our acceptance. Criteria. Cep does not clearly provide an indicative list

and specifications of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device. so to determine accessibility, acceptability of the benefit to risk ratio of the device, performance and safety outcomes the methods used, for example, objective clinical tests. validated, prompt questionnaires, etc. And the acceptance. Criteria must be defined, based on state of the art, including product specific standards, if possible.

What people often forget is the clinical development plan. According to the annex, 14, part R.

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The manufacturer does not provide a clinical development plan for legacy devices. People always think that this plan only has to be submitted or to be included if we have new submissions. But this is not correct. However, considering the regulatory status status of legacy devices, this level of detail is not expected, and rather the Cdp. May focus on the strategy to obtain clinical evidence in line with Mdr. Tickle 61 requirements. And of course, the planet Pmcs activities. if applicable. Cdp should also always include a justification for any deficiencies in relation to previously conducted first, st man studies, feasibility or pilot studies, confirmatory investigations.

noting any reference to Pmcf activities that are ongoing or reference to the Pmcf. Plan are described in Annex 14. So now we have the biggest pitfalls for the Cep, so that we could go to our beloved clinical evaluation plan report and the 1st pitfall there is the Update frequency. The update frequency is not clearly defined in per Mdr. Article 62, 11, where it said that the clinical evaluation and its documentation shall be updated throughout the lifecycle of the device concerned with clinical data obtained from the implementation of manufacturer's Pmcf. Plan in accordance with part B of Annex 14, and the post-market surveillance plan referred to in Article 84.

So clinical evaluation must be updated throughout the whole lifecycle of a device. Of course, with clinical data from Pms Pmcf processes. And of course, we, if we have any major events, or whatever what happens, records or whatever we have to update this. And as this is not clearly defined in the Mdar regulations. The expectation is that manufacturers align the frequency of clinical evaluation updates with the guidance currently available from the Medef 2,001 revision 4, and based on this guidance. The clinical evaluation should be updated minimum.

When the manufacturer receives Pms, including Pmcf information which has potential to change the current evaluation. it has to be updated at least annually. If the device carries significant risk, or if it is not well established, otherwise, it has to be at least updated every 2 to 5 years. If the device is not expected to carry significant risks, and it's well established for the class 3 and implantable devices. An annual update should be considered anyway, the manufacturer is expected to justify the defined frequency for performing the updates of the clinical evaluation.

Very important part of the evaluation is the defining of the state of the arts. State of the art is not clearly defined, is incomplete, and is not clear how the acceptance, criteria for safety and performance outcome has been established, based on the state of the art. So evaluation of the device within the context of state of the art is essential for demonstrating that, when used as intended. the benefits outweigh any potential risk.

So if you're working with a client chef on. and they come to you. And they say, you know, we need to define state of the art. What? What do you tell them, you know? Like, let's let me derail you for a minute.

Yeah, of course. for a starting point to define. For the whole analysis, manufacturers must define the state of the art for their device. So this is critical. As this fascillates the characterization of the expected clinical performance and the the resulting clinical benefit, the clinical safety profile for the device under evaluation. And this is very good question. I just go one. No, I it's too early. It's coming a little bit later. See there here, because it is very, very crucial when we are defining the state of the art, that the literacy search for state of the art has to be completely different to the literacy search for our clinical data, for our evaluation of our Gsprs. And this is often

also not done by the manufacturers are often forgotten. We have to put this in this our literature search plan clearly defined, our searches for state of the art clearly defined, our searches for the political data, and they all has to be justified. And it's also one of the biggest biggest pitfalls for the notified bodies, the biggest deviations there that the state of the art, the search. Literature, search for state of the art is not clearly defined and is not justified. Has this answer to your question, Sean.

Yes, yeah. And if there's time. Lisa also has a question.

Is it possible that we put these questions to the end.

Possible.

We started quite lately. So I'm would like to go through a little bit, because I want, of course, do what is enough. sufficient, absolutely data. But I have to put just put on the grounds here. It is not so long anymore until we come to the interesting themes. But so if it is also okay for you, Lisa, I would like to put the questions to the end. Okay.

Sure. Thank you.

So this is exactly what we will talk about. This is what is sufficient clinical evidence. This is also put this a little bit afterwards, because it's a total. The bigger things that I will talk about just for completeness is already mentioned. Here also. conclusions racketing, accessibility of the benefit to risk ratio do not consider all available data. This is also that lot. Sometimes, also, in my experience, the manufacturers don't want or don't mention. If they had adverse effects or negative impacts on patient management over public health. And this is, of course, a big, big

disadvantage. And of course, this will lead to a negative impact. The device lifetime has to be clearly defined in the Cer. This can be defined in minutes, days, years, months, or whatever, or just like I mentioned before. In case of implants which are not intended to be removed. the lifetime of the device is equal to the remaining lifetime of the patient. When we start our clinical evaluation, we have to choose our strategy strategy chosen for clinical evaluation or the rationale for applicability of the Mdr article 61 requirements are not clearly presented in the clinical evaluation documentation.

So, Mdr. Article 61. This already describes different options for clinical evidence to support conformity of the device. Level of clinical evidence selected by the manufacturer is dependent on several factors, including the risk classification of the medical device and its regulatory status. So what people always forget, and what is, in my opinion, very, very, very important. When you look at the FDA clearance normally, all people go in the precept before, and people often think that is not possible in any way when you have to want to see emark your product. But this is not true. I only can recommend, go in dialogue with your notified body.

Most common reasons for delays in technical documentation by notified bodies are incomplete submissions, and you insufficient or missing information not provided that is required for the conformity assessment activities. This includes an incomplete or inconsistent description of devices covered by the application and the related technical documentation or variants accessories, combined devices that are covered by the basic Udi to be assessed. You have a lack of cohesive structure of technical documentation. Information is presented with a technical documentation, but it is difficult to locate. To avoid delays and to further improve your submission. Please consider the practical

following practical points. I can only recommend, go in communication with a notified body before you start an application. So if you do this. you should contact the notified body to clarify language requirements for technical documentation, submission of the individual notified body. This is mentioned in the Mdr. Article 52, 12. I think manufacturers should contact the notified body to clarify requirements related to documentation in labeling methods for submission to the notified body, additional guidance on topics suitable for the discussion of notified body prior to the submission

so also provided in the Mdcg. 2019 6. This is must be section 1, 6, 3. This is the so-called structured dialogue. so structured dialogue takes place before the official application of an Mdr. Or Ivdr. Application is submitted to the notified body. Dialogue is intended to clarify timing procedure. Regulatory aspects of the application process and serves to answer questions about application forms, documents to be submitted. Structured dialogue, very important, is incompletely independent of the conformity assessment.

including a discussion with the customer before the customer submits the actual application for conformity assessment. For this reason, and to demonstrate independence, neutrality, and objectivity. The structured dialogue service offered by a notified body is commissioned separately from the Mdr. Or Ivdr. Framework Agreement. So what can we ask possible topics and questions for the structured dialogue. application and onboarding the onboarding process. Application forms, application revenue processes, the location suppliers, products, product classification, the code assignments you can ask about testing certification regulations, Mdr. Or Ivdr. Framework agreements dealing with the medical device possible changes.

And if you want to change to another notified body the project planning dev project planning deadlines for special procedures, obligations to submit costs, fees, other economic aspects, common specification guidelines and harmonized standards that we have to use in our assessment procedure. So I can only recommend to use these things so that you will have a much, much smoother application. We'll have now a look at the top 5 Nonconformacies. which are taken out of the reviews of notified bodies. So this is the practical part. Yeah, what is most that notified parties do not accept.

This is top one safety and performance parameters and the threshold values equivalents of other devices. Pmcf. Activities the literature searched, as I've mentioned before, and the clinical claims. safety performance. Parameters and threshold values are not determined or unsufficient. or the acceptance criteria or the values are not defined. What's often happening is that in the state of the art research. You see a visible outlier, and the manufacturer takes this as a threshold value, and this will not be accepted by notified bodies.

Equivalence, just for all the people who are joining this call here from the States has a different view to the equivalence of the FDA. Yeah. So here equivalence is required in all points meaning clinical, biological, and technical equivalence. and not a partial equivalence with various products. So we have to focus on the description of similarities and scientific evidence of the lack of negative impact on benefit risk ratio, which is all described in the Mdtg 2025. If you look at our Pmcf activities. It is often noted that inadequately selected Pmcf activities.

for example, for the equivalence of a novelty. have gaps in clinical data missing studies. For example, if I have a device that can be used for children and for adolescents, I have, of course, to put clinical data for all ages inside insufficient integration of safety and performance parameters in the Pmcf. Activity or the lack of quality. We have good bad user surveys, or whatever. This is just to be complete already talked about. And Sean gave this question. There we have to do a clear breakdown of the literature, search into the device under evaluation and the state of the art, and we have to justify this, and of course, not to mention normally. But we all have to submit all full texts that we are using in our evaluation

clinical claims is a very, very crucial point, and the lack of clinical data to support these clinical claims often also. all clinical claims made in the promotion material website that should be supported by sufficient clinical evidence in the Cer manufacturers very often forget what claims anybody has done on their website in the promotional material or whatever. And if we see or notified body sees this afterwards, then we already have at least little problem for this other points that are very, very easy to solve. But it always occur. Please look that we have consistency in all documents.

Technical documentation. According to the Annex, 2 of the Mdr. And, if applicable, the summary thereof to be drawn up by the manufacturer, shall be presented in a clear, organized, readily searchable, and unambidious manner, and shall include in particular the elements listed in these annex. It should be submitted in a Pdf format, and we need a clickable table of contents and bookmarks. and of course, all relevant documents. Cpcr. Ifu risk management, slc, peer will ever have to be submitted so that nothing is missing. So

these have been the biggest pitfalls and the parts of the notified body there. And now we come to this part. where we see what are the requirements of the different pathways. What pathways can we take to receive? The emac! So there is our normal 1st submission. When we need clinical trials to get clinical data. we have legacy devices, we have wet devices, the so-called well-established devices. We have orphan medical devices. We have customer-made devices. We have devices that are falling under the article Mdr. 61, 10. And now we will look in detail. What are these ones?

So what is the well-established device? According to the Mdcg. 2026. Medical device regulation 2017, 7, 4, 5 does not provide a definition. What a well established technology is. The Mdr. Only mentions devices similar to those listed in Article 61. Paragraph 6 B. What are named sutures. staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins. clips, and connectors, Mdcg. 2026 fills this gap and emphasizes that well established technologies do not exclusively compromise the products mentioned above, but also similar devices. So our characteristics for wet devices. They have to be simple.

common. and we have to have a consistent design with little further development. The generic product group is known to be safe and has not been associated with safety issues. well-known performance characteristics, the standard of care products with little further development, and they have to be on the market for a long time. So, from view of the Mdcg. 2026, all products that meet these criterias can be considered well established criteria technologies. how do you also define what are legacy devices, their existing products that have been on the market under the already under the market, under the medical device directives.

I'm at Mdd. A. 93, 42 Ec. Or Amdd. For Ivdrs. A product of well-established technology can therefore also be a legacy device at the same time, but has not to need to. Of course, for legacy devices. Yeah, there is clinical evaluation necessary. Mdcg, 2026 clarifies that clinical evaluations based on sufficient clinical data are required for all devices, including devices identified in Article 61. Paragraph 6 b. Of the Mdr. However, subset of devices does not necessarily require clinical investigations, even if the devices have not previously been ce marked, and are also class 3 devices or implants.

However, this only applies to the aforementioned group subgroup and not to well-established technology devices in general. So I wanted to show you here a little bit in practical, what are well-established devices. I took out here for cardiology. And how has this been justified? But in order that we already have much, much time, I will go through this very short, and if you have interest, come back to me later, for example, well established technologies in cardiology, ablation catheters using radiofrequency creo energy. These are diagnostic electrophysical catheters. leads for cardiac pacing, defibrillation, diagnostic therapeutic catheters for coronary and structural interventions, or diagnostic and therapeutic intracardiac devices for coronary and structural interventions and the justification for earth to be important. That we're accepted by the notified bodies is nearly always the same, so that this device has been on the market for more than 20 years.

and that this is a device with no or only minor modification, or without any safety issues through the last years. Just like, I said, if you have interest in this. Come back to me later, please. Yeah. We'll now have a look at the article 61, 10 of the performance-based approach. which is only for medical devices without direct clinical benefit, which have no clinical claims and which have no clinical where no clinical data is possible. Notified bodies do never accept the justification that clinical data is not available just to notice. So what is the article 61, 10 of the EU Mdr. It provides a route for manufacturers to demonstrate that the medical device meets safety and performance standards

without clinical data, while clinical evaluation is essential for proving compliance with the dsprs this article applies to devices for which clinical data is not deemed appropriate or necessary. This provision is especially relevant for low-risk devices, or those that do not have clinical directly impact. So this option, therefore, is not available for class 3 or implantable devices, so it should be applied to lower risk devices where the performance can be sufficiently demonstrated. Non-clinical data, mechanical mechanical testing, performance, evaluations, or other bench testings.

What are devices that normally can be eligible for this under article 61, 10 certain types. Medical devices are more likely to qualify for non-clinical data to demonstrate compliance. These include dental treatment units, mouth speculates, operating lights, patient positioning systems, standalone software. blood glucose meters or wheelchairs and walking aids. These devices typically do not require direct evaluation and may not provide clinical benefits making clinical data unnecessary. Instead, performance and safety can be proven through non-clinical means.

Manufacturers still have must justify where clinical data is inappropriate. And just like I said, it's not accepted that no data is available. Justification must be documented in the Clinic Evaluation report. It must include the risk management with potential risks and hazards associated with the device under evaluation. Effective mitigation of these risks and interaction with the human body, devices that have limited or no direct interaction with the human body are more likely to qualify for 61, 10, intended clinical performance. and the clinical data will still be necessary if clinical claims cannot be verified through non-clinical testing.

When should Article 61, 10, be used. This pathway is most relevant in for legacy devices that were previously Ce. Marked under the Mdd. Or Amdd. Have a strong track record of safe and effective use for well-established devices that are based on major technologies that have documented safety and performance profiles for low risk devices. Class one or 2, A devices where the risks of conducting new clinical investigations might not justify potential benefits. higher risk devices, such as Class 2 B, and 3 proving equivalence and meeting the required data standards can be more challenging. Manufacturers may need additional justifications or consider conducting clinical investigations if necessary. So article 6,110 pathway is a valuable option for demonstrating conformity with safety and performance requirements. When appropriate clinical data is not available.

Particular advantages for legacy devices and well-established devices that need to comply with the Mdr. Often devices something that's also lying on my heart. Yeah, because a lot of often devices will vanish from the European market. Yeah. So the Mdgd 2024, 10 is aimed at manufacturers of niche products as well as the responsible authorities and notified bodies. Because, of course, all submissions. Costing money for the manufacturers, and to order not to lose all orphan devices on our market here Mecg at least gave some solution. Approaches would like to provide stakeholders with assistance and clinical evaluation.

It points out, permitted restrictions on clinical data that are collected prior to marketing in particular, and considers extrapolations of data from other populations to be acceptable under circumstances. For example, if they can be balanced via post-market activities. also those attention to other data sources, such as equivalent products, registries, and also off-level use. We would like to support the approval process by providing notified bodies with assistance in the assessment. This is the so-called certificates with conditions describing the roles of expert panels. However, it is still unclear how manufacturers will benefit from this

custom made devices also mandatory for clinical evaluation under Mdr. 2017. For 5. They're unique. What makes it very hard to generate large scale clinical data. Literature reviews and Pmc data are used instead, and extensive documentation can be source intensive for small manufacturers. Anyway, there's still another approach to gain clinical data via Cmds. As they can be used as equivalent device for Ce marking, which is not the original thought of Mdr. But what is legally possible anyway, the very, very good point now is what is sufficient clinical data.

It is not clearly defined in the Mdr. What is sufficient clinical data, how much data is sufficient in order to demonstrate, compliant with the relevant Gsprs. Sufficient clinical data must be presented for all medical devices in the clinical evaluation. But what is it really scope and quality of clinical data deemed sufficient for a product should be determined by the manufacturer and has to be justified in the clinical evaluation. The risk class, and the intended purpose of the device should be taken into account. It is still unclear if the plan and Iso 8, 9, 6, 9, 9. Standard for clinical evaluation will bring more clarity to this topic.

So, according to the Mecg. 2026, appendix 3, we have different kinds of clinical data. I think this is very, very small here. So I put this up in 2 parts. Yeah. the rank, 2 rank, one. Clinical evidence is high quality clinical trials across all variants, indications, patient populations, rank, 2 high quality clinical trials with some gaps, rank, 3 high quality clinical data collection systems, registries for studies with methodological weak links, the data must still be quantifiable. Rank 5 is equivalence, data, rank, 6. Data from similar products from state of the art.

7. Complaints and vigilance data of our product. 8 proactive Pms data, such as surveys, 9 case reports. common specifications, non-clinical is 9, 10 simulated applications like animal cadaver tests on 1011, sorry and preclinical, and bench tests. Compliance with standards is our rank. 12. So just come back there. Rank, rank, one to 4 can be used for performance requirements and for safety requirements. And as we can see here. rank 5. Our equivalence data can be used for both data from similar products, from state of the art are supportive for both

our own complaint and vigilance data can't be used for performance, but can be supportive for safety. Proactive Pms. Data like service can't used at all. Case reports we can use as supportive for both and rank. 1011, 12 can prove clinical endpoints. But as there's no clinic data. This is not relevant to us. This is just the big one, and no sorry. Sorry I have to go back. Just look now again, what kind of device we have. If you have a legacy, devices of class 3, an implantable

which are not vet, we have to take a combination of rank 1, 2, 4. Our well-established devices can be says through a combination of rank, 5, 12.th Look now for different combinations. What is enough for which type of device. We have data for vets. If you have only 10 to 12, and data from our similar products from state of the art which can only be supportive? Is the question, could this be enough? And this could, of course, not be enough, as both data don't meet the requirements of clinical data which are specified in the mer.

And here I should check if 61, 10 is maybe eligible. If you combine data from 6 and 7 meaning similar products supportive, and our own complaint and vigilance data which we can't use for performance. It's still enough if we now can add case reports to this our rank. 9. This will be sufficient for low risk devices, but not for high risk lows. Yeah. what about products that are out of the scope of the Mdcg meaning class 1, 2, non-vet with low risks. So for them still appendix 3 of Mecg. 2026 is mainly applicable, meaning.

We can use a combination of clinical data from 6 to 12, but not from 5 to 12. Sorry, but not 6, meaning the similar products from the state of the art class. 3. Implantable non-vet devices with high risks always have to get a combination of ranks, one. and the people here in this call especially, I always think, who are joining us from the United States. They have the big advantage. If they already have FDA cleared devices that they can also use real world data, respective real world evidence if they are aiming for further on

ce approval. And as I just mentioned, while we started, I was thinking about having a very, very short look at the clinical evaluation of Mdai new guidance. But as the time went out. I will skip this now, and just show you well to give it to your heart if you ever want to submit an application for Cemark to a notified body. Here. please align your Cer with the template. Mdcg. 2020 13. This is the clinical Evaluation Assessment report, which is also used by the notified bodies. Evaluate your report and your submission. If anybody is interested in this, have any questions or whatever.

Please contact me. either via email or Via Linkedin. You can just use this QR code here, and I can, of course. assist. You can answer your questions, which are still open, and I can also give you these templates if anybody is interested here. So this is at this time I would stop my presentation, and I hope there's still a little bit time for the open questions. Thank you very much.

Thank you very much. we are almost out of time. I wanna make sure that I mentioned that next week we will not be meeting due to the 4th of July and the following week we're gonna have 2. Sarah's presenting on digital transformation. So I wanted to get that announcement in before we go to questions. There were a number of questions in the Q. And a. Unfortunately my thing disconnected. Are you able to see the question, Stefan, because I cannot.

And let's let me look.

and we had a number of requests for the presentation. So please send me a copy of that, and I'll make sure that they get it as well.

Yeah, no problem, no problem.

Adam.

Nice job.

Oh, hey! Chris!

Hey? Thank you for promoting me now you can see me.

Well, there were 2 of you before, and so I just picked the wrong one.

Yeah, I was my, I was getting my butt kicked trying to log into this thing. So I'm amazed that I actually got into this thing.

I'm glad you made it.

Very nice presentation. Stefan. Nice job.

Thank you very much. So I don't know how. Maybe because I just showed my presentation. I just can't see this Q. And a questions here. Maybe, if it's possible, I can only offer you.

Here we go!

These questions to me. Drop me a message and link it and drop me a mail, and I will answer all. But I don't know why I can't see them all, or Sean, do you see? Can you give them to me, Sean?

No, and unfortunately they got wiped out, but I might have a record of them. I I momentarily lost connection to zoom during during the call. It shut down unexpectedly, was the message Zoom has shut down on. I panicked because I thought the call had ended but apparently it hadn't. Anyway.

I just shared them in the chat.

So right, there's 1 in the chat. How an indirect clinical benefit impact the overall cer, for example, is it enough to focus on product performance do equivalence strategies, equivalent strategy always requires specific Pmcf activities or do general Pmcf activities suffice? Yeah, if.

You have an equivalent strategy. You also have, of course, in the Pmcf. You have to look. What is the equivalent device? How is this performing? Are there any safety issues? We have to look at the so-called beef harm? Yeah, where you can look if there's been any adverse event or whatever. So this is meaning that you have also have the equivalence devices. But please don't underestimate that equivalence device. Strategy is not as easy as it was under the Meta version 4, you have to have all the 100% clinical, biological, and technical equivalents, and you have to have access to all data of the technical implementation of this other product, so meaning this can only be a big manufacturer which has the same in-house product.

But normally nobody will give you a contract that you can see all our data from a device when you are congruence. So this is very, very difficult to get this. It can be used for lower risk devices sometimes. But it is not the normal way anymore.

Fantastic. Well, on that note, if you have any questions that did not get answered, please forward them to me, and I'll make sure that Stefan gets them. And if you have any questions, please let me know anybody who's interested in submitting an article for the 1st issue of Expert Pov. The new publication from Medtech leading voice exchange. Please contact me with your article idea, and we'll work it out. That's it. I hope to see everybody in 2 weeks. And look forward to digital transformation. Thank you again, Stefan, for your time, and everyone who attended.

Yeah, I thank you. All people who joined this call. I hope you enjoyed it. And so if you have any questions, if you want to have any template or whatever feel free to reach out to me. Thank you very much for your time.

Nice job. Thanks. Sean.

Thanks very much. Bye, bye.

Everyone. Bye-bye, happy weekend.

A feed is in.

Very nice.

Yeah. Have a good weekend.

Same to you. Bye-bye.

Bye.

Take care!