Friday In-Focus State of the Art – From Claims to Strategy

So, I'm gonna let the other people in. I made this program so much. Attendees… Okay, yellow… Promote piano list.

Hey.

Good morning.

Good morning.

time, we'll see. Did you speak up, yo?

Yep.

Okay. I just listen if you are loud and clear.

Check my mic.

Yeah, you can speak a little bit.

Okay.

Louder. I'm not sure if we see other people also joining, or… That's a heart saved them. Oh, we're recording now.

Now, I see already 6 people in the call. Oh, good morning, Michelle.

I was hoping we could see the arrest also.

We'd at least already start sharing.

Very good.

Do you see?

Yeah, yeah, it was good, yellow. Next up, we'll promote you, Oh, she's there. Bye, baby.

Okay.

So I wanted time to fix my hair, but it didn't happen because of technical difficulties. I swear I'm moving off this platform as soon as possible. But in the meantime, it is 11am, and I would like to welcome everybody to Friday in Focus. I'm super excited about today's presentation with Robert Vin Buxtall and Yella. Schwiring… doing my best, and… I'll let him say his own last name. And, to talk… to talk about, strategy, for med tech, from a perspective of state-of-the-art in claims, which I think is a super interesting take on this, one that I haven't heard before, and I am going to…

turn it over to Robert Miela. Guys, hi, welcome.

Thank you very much, Sean, and thank you. Yeah, you pronounced my name pretty well, Robert von Buckstall, Yellowstone is a different name, it's a different, pronunciation, it's something very Dutchish, the first letters in his last name. Nonetheless, thank you, thank you for inviting us, thank you also for, for, rescheduling, because there were some technical difficulties, thank you also for, for, yeah, being very honest on that, and, thankfully, we're now here. Yay! Okay, very good. I see some people are already joining, Yeah, so how do we recover from this? I'm sure we will, Sean. So, let's do the introduction. I think that will be much more, useful. So, we are both working as consultants in Medical Life Project, which is a

a Dutch consultancy company, and, the two of us were very highly involved in, several elements that are linked towards the regulations, clinical risk management, part of that. And, we'd like to explain the concept to you. So, yeah, so, Yellow, maybe you can introduce yourself first?

Sure. Thank you, at least as well, Sean, for inviting us. Currently, I'm a senior consultant in medical device projects, been doing that for two and a half years now. Before that, I spent some time, 7 years, I believe, at a multinational. Developing medical devices, bringing them to market, and I have a background in both engineering and a PhD in medical device technology. So, well, here I am.

Beautiful. Myself, I'm with the project for a little bit longer, like, over 15 years now. And before that, I worked with a notified body, it's called DACRA these days. And also, I did work in the industry, in plants, in different roles, different, different manufacturing locations, lots of background. So, the… oh, yeah, and, biomedical devices, yeah, that's my, that's my education, so, So, yeah, I think we have an interesting, interesting way to go forward on this, this hour that we have together. We'd like to bring you into a new concept that we think is very useful, independent of whether you need to meet regulations or not, independent of where you are in the world.

And whatever your regulator wants, or the regulators of the areas where you bring your devices on the market. And so we like to explain to you the concept of state-of-the-art, which is indeed a very broad concept that has been promoted by the IMDRF already for some time. And, we'd like to make it a little bit more practical. And that's, that's our approach here. And every now and then during the presentation, we'd like to stop, and we'd like to Ask you to provide us with some feedback. And first, I'll introduce the whole concept, and then Yellow will explain from from regulatory and international IMD rep point of view, what state of the art is, and how you can apply it, and then we will move on a little bit further into further discussions on how that can be relevant for you. Maybe you come up during our presentation with some questions.

So we take those breaks to… to look into whether questions are posed on the chat, or whether you have your hand raised, or whatever. So, if you can be… you can raise your hand, but you can also, would like to be a little bit, how do you say, patient until we meet that point of break. Is that okay? Good, good, good. So, state of the order, what is it? What should I do with it? Is it required? The best practice? What's the link with other companies process it? And can I actually do something with it? And then we also would like to discuss claims, because, you know, what are claims? What do we mean with that? Well, basically, what is your product doing, and how can you prove it?

But we'll give a little different swing to it. Next, yellow? So, one of the things we'd like to take you along with is that there's a lot of strategy determination happening in companies, and you might be actively involved in one of the different layers. But you have to realize that, all these different layers, they provide input to each other, and, going from, from, from corporate perspective, top management strategy, to business unit strategies. Startups typically are a little bit… starting a little bit lower, you know, what market do I want to access, and where can I actually make some money on that… on that part. Then we go down, where you need to start thinking about your product portfolio, or you already have a product portfolio.

Also, what are the claims that we are going to put in place on our devices? And, yeah, if we don't have anything yet, how can we develop a device that is actually, can be tested to also support these type of claims? So, it's really a high-level flow all the way down to design and development. But where does this soda now come in? And also, yeah, so we use the abbreviation, state-of-the-art SODA. Is it a burden, or should you see it as an opportunity? And here, I would like to pause for the first time, and I'd like to open the floor a little bit. Do people here maybe can spend a little bit of back-and-forth discussion from your experience? How do you see state-of-the-art, and are you using it in anywhere of these strategy locations?

Is there anybody who would like to provide some feedback here? I see, Stephanie. Hi, Stephanie! Going back. Too many definitions to soda? Okay, that's good, that's good. We'll go into definitions a little bit later. People out there who'd like to comment on their experience with soda and how they use it. Yeah, yeah.

I personally, struggle… struggled with this definition from the very beginning, because it It really doesn't mean what it sounds like.

Okay.

That's good, that's good, that's good. Yeah, I see, Viet, you're, you're, you're responding also on, on the fact that, notified bodies are asking for it, and it's everywhere. So how about we go to the, to the everywhere? Yelos, we move to the, to the next one. So, the strategy, or actually, I should say, the strategy for regulatory compliance is something that, from a European perspective, needs to be established. But also, if you even if you're not European, it doesn't matter where you are, if you have a company to drive, you need to strategize, you need to look into what areas, what markets am I going to approach, and what is therefore needed from a regulatory perspective.

So how are we going to determine these requirements, and how do they fit in with quality management system? And how do they fit in with the expectations of the user? Because do you actually know the expectations? of your user, and how can you analyze their expectations? What is the field of play? What is the… What is the aim that I'm going to take? What am I going to hit when I throw my darts? And am I really going to be on spot there? So what is really happening in the world, in the clinical field where my devices are going to operate? or are going to be used. And it's a very close link towards the business strategy, meaning, what is… what is the… what are the opportunities from a business point of view in these specific markets and these specific, applications of your device? So,

So that's what we think is the link also towards the claims that can be made, once you know your business, once you know where your device is going to operate. So, from our view. without still knowing what SOBA exactly is, we're gonna explain, no worries. The… you can use that information, and… and you should… you should transfer your… your story and… and your thinking also towards, strategizing and towards these, these, these management terminologies. You need to be able to strategically market your device and know how to get that access. And knowing what the SODA environment is that your device is going to be working in really helps also towards claim management.

Okay, next. Yeah, yeah.

Yep.

Okay. So, let's go a little bit, I'm sorry, European, but there's some Europeans here also, thankfully. From a European perspective, so we did a little bit of accounting. And, yeah, there's, it's very interesting. We found out, actually, that, there is not really a definition, and, that's, what Beat also, so indicated on the, on the chat. You know, nobody really knows what it is. It's not really a good definition, it's mentioned in the MDR, etc, etc. But Yellow is going to explain a little bit about what it means and how you can actually use it. So, yellow, the floor is yours.

Okay. I already see some interesting things coming in onto the chat. I think it's quite relevant to this slide, actually, but maybe that's for the rest of them, for the rest of the audience. Let's go over it. Because on the top, you see quite interesting definitions from the IMDRF. you just learned from Robert that there is no actual definition in your… in the MDR. But IMDR talks about this definition in the text box here. It's interesting. You need to read it maybe two, three times before you completely grasp it, right? It talks about a technical capability, maybe also what's accepted in clinical practice.

Patients come along, and it also concerns consolidated find… consolidated findings in science, technology, and experience. Fair enough. But, at least in our business, Robert and I, we often also speak to SMEs and, startups, family business, if you will. If you then want to explain it, I think the MDCG guidance in 2026 is actually a little bit more useful, which says, state-of-the-art embodies what's currently and generally accepted as good practice in technology and medicine. And I already saw it coming in the chat as well, so I think someone in this audience knows definition. I think this one is a little bit more practical, right? So, what is currently generally accepted as good practice in technology and medicine?

Or… If it's more simply put, if you're a physician, what devices do you have your… have you… do you have at your exposure? to treat a patient. Can also be a nurse, of course, or maybe even the patient themselves, if you're talking about over-the-counter products.

Yeah. Oh, we also saw…

Yep.

Yeah, I have a question here, you know, the… it says state-of-the-art, but it also says state-of-the-art with hyphens. So now we're getting a little bit confused on this, on this here, and I see there's some comments in the chat also on that. Can we… do we have something to say on this?

I think maybe you can explain a little.

Oh, okay, yeah. So we borrowed something from people that were very handy in trying to explain the difference between state-of-the-art and state-of-the-art with hyphens. And, Christopher, thank you also for your point of view there, the noun and the adjective. The… basically, state-of-the-art means that whatever is happening with your type of devices in the clinical or maybe even a home environment, but it doesn't necessarily mean that's the best of the best. In the state-of-the-art with the hyvens. Typically refers, and it's also when you, when you search on the, in, in dictionaries, and I just have one example here.

It really focuses on the definition of state-of-the-art with the hyphens, meaning the best of the best, or the highest, or the whatever. So that's not what we are talking about here, so that also needs to be very clear. So we are talking about state-of-the-art without the hyphens. as referred to in the MDR, and not, the potentially not well-written MDCG, that, that we just put on the screen. So, thanks again, Christopher, for your, for your contribution there also. Okay, so let's go on.

Sharp. So next slide. Indeed, again, we're talking about a European perspective here, because there it's mentioned. And I appreciate that most people on this call are very senior, but maybe just still I want to mention that the MDR is a general regulatory framework, right? It needs to cover everything from a Class 1 device, let's say a wheelchair or something like that, to a Class 3 implantable. So this general framework also talks in general terminology, like normal, relevant, sufficient, appropriate, acceptable. It doesn't really specify per device what you should or should not do, or what you should be capable of, right? So, just as an example, I'm not going to read the entire text box, of course, but this is in the text box, you see Article 61, covering the clinical evaluation.

And there you see some of these wordings already coming up, As we read along, right? So it talks about, in bold, the normal conditions of the intended use of the device. So what is normal, right? How should you normally use that device? X talks about acceptability of the benefit-risk ratio. With providing sufficient clinical evidence, though, and sufficient And goes on, also, again, about the level of clinical evidence that should be appropriate. So there's lots of, let's say, subjective wording. And it's then up to the manufacturer to give meaning to this. And basically, the point here is that state-of-the-art analysis can give a basis to this.

Right? So… the MDR is actually riddled with this kind of wording. And maybe I think most people on the call also know MDR, you have 23 GSPRs, or General Safety and Performance Requirements, right, that, that your device should meet, if relevant. And the first one, in my mind, is sort of like the umbrella GSPR. It's a big one. It says, okay, your device should be suitable for the intended purpose, okay, it should be safe and effective, fair enough. And also acceptable risks when weighed against the benefits. Okay? And then it ends with taking into account the generally accepted, or the generally acknowledged state of the art.

So… Here we go again with the wording. What is suitable here? And also safe and effective. When it's something safe, right? If you're, gonna implant a hard valve. you're gonna know you're gonna have some side effects, so that might be acceptable, because otherwise you'll die of heart failure. Right? So, how do you know when the risk is acceptable, and how do you weigh those benefits? And I'm talking about… talking about the clinical benefit of a hard file, but also risks, right? So risk management also comes along in GHPR4, for instance. It talks about risk control management measures, and it specifically, again, mentions the acknowledged state of the art. So, alright.

Also, State Yard also helps, identify your risk control measure, shapes your risk management. GSPR8, for instance, and these are just examples. Also, side effects, right? When are side effects acceptable? How do you know that? Next one, BMS, right? It says about relevant data, okay, what's relevant, so if you have information people don't like your box because it's the color green, that might not be relevant. Or if you get new information that, I don't know, that stroke rate increases after implementation? Well, that could be relevant information, right? But you should judge them. Also want to call out this one in the… in the annex about clinical evaluation. It talks about alternative treatment options, so you keep your eye on that.

If there are better options available, does your device actually have a place in the market, right? Have you earned it? And the clinical evaluation plan, also, again, based on state-of-the-art medicine, is called out, and here, then, in terms of the… in light of the accessibility of the benefit-risk ratio, and that you need parameters for that. Okay, so here you see lots of, let's say, subjective wording. That's… Relate, to the state of the art and should give meaning as a manufacturer. Okay. Just a quick slide also, maybe, on the… on when this created state of the art. I think if you all know, clinical evaluation and risk management are continuous processes, so it cannot be you do a clinical evaluation report or risk management report. You do them once, you put them in the dryer, and you're done. No.

So state yard, they need to be updated, and therefore state yard also need to be updated. One important point here, maybe for the people on the call is, if you have devices that are still under MDD, and you need to go to the MDR for the first time, in the transition period, or… already a long time into that, but maybe it's still happening. Please know that the update of this state yard can take quite some time, right? On the other hand, if you already have new devices, in our experience, it can also help you, actually. So, you can start with a clinical evaluation plan, but the information that you gain from that can maybe also still serve as good input for your design and development process.

Once you have it in the SAP, you can finally update it in the clinical evaluation report, and then submit it to your notified body. And then in the post-market phase, okay, you can keep updating your state-of-the-art with, for instance, your PMCF activities, right? So this was a little bit on… When to create the state of the art. And as we're talking about the medical device regulation, I want to touch upon one key point, and that's the acceptability of the benefit-risk ratio. This is something that you need to do, right? There's no way around it. It's in the MDR. You see some quotes that we give in there on the top. The benefit-risk ratios, for instance, mentioned GSPR 1 and 8.

There it specifically calls out that, yeah, that the risks should be acceptable when weighed against the benefits. And that's also in the… text of the annex are about how to, what should be in a clinical evaluation plan. State of Yards also mentioned. So, on the one end of the scale, you have the benefits. You need to know something about your benefits. So… you need to stay in the art to say something about, okay, what is then the clinical performance that you expect from your device? And clinical performance, but also the clinical benefits that you will eventually have for your patients. and how are you going to measure that? What are the clinical outcome parameters, right?

If you do an assessment of the state of the art. what's generally accepted, you know, in cardiac surgery? You know, okay, what's then the clinical performance likely can be from a new valve implant, let's say, just as an example, but also what are the outcome parameters that come along with it? And we'll dive into that a little bit later on in this talk. But that's the benefits on the other end of the scale. You also have risks. So, what are known risks? What are side effects? What are acceptable levels? State-of-the-art can help you define all this. If you have that, answering questions was, I think, also in the chat about the GSPRs is, maybe a little bit more

Doable, actually. Right? I also saw a comment in the chat, I don't see it anymore, but it was also more towards the clinical process, so yes, state-of-the-art obviously closely relates to the clinical process. First, in the planning phase, you're going to write a clinical evaluation plan. So there, you're going to determine, okay, what are my preliminary clinical… the level of my clinical performance, and the level of clinical safety. When you know that, you can also determine, okay, how am I going to evaluate my benefit-risk ratio later? the… then go through a clinical evaluation report, and there you will, well, make the conclusions. So, in essence.

How high do you need to put the bar to earn your place on the market? And it's just not clinical, it's also risk management, you know, the side effects that we had, the safety outcome, severity, whatnot. It relates to PMF, PMCF, Because if you know what you're still missing, you can steer your PNCF activities, for instance, or you identify new risks. It can help design development, and on the bottom, and it will only be the second half of this talk, is claim management, right? So, from state-of-the-art to claim management. Alright. So, in all, we… the… let's say the concept that we use with our clients is the main elements of the CDR that we build is actually fourfold. We determine the suitability of the purpose and indication. It's helpful for the definition of the clinical benefits and the clinical outcomes.

It helps to define your risk levels, and all that together is actually your basis. To assess the benefit-risk ratio. Right? Also, yeah, these elements that, that are identified here, I think, are extremely important, as a, as a, you know, from a technical, clinical point of view.

To, to realize for the audience that, if you, if you, if you're not able to determine these different, these different elements from, say, the art. And use them towards your design of your device, then it will be really difficult to know what you're aiming at, because, yeah, it's sort of your big aim, this is what we need to establish, this is what we need to do. And also, the question that we have is, are there any additional comments on that, on the theoretical part of State of the art that people would like to share with the group? Is there… is there, anybody who would like to speak up? Can they speak up, actually?

Michelle, we can't hear you. Sorry. People can put themselves from mute, or…

I see Sean nodding.

Yeah, Sean is nodding. Okay, good. Okay, so if you have any additional questions on this, this concept of the actual, okay, so we have, Goldie indicating… okay, good. We're agreeing with Goldie.

Yeah, very nice to hear.

So, what we're now going to do is actually a little… one step further. We're going to put in an example, and discuss, based on this example, how you can make these, these, four elements actionable, because I think that's what we're… what we need to do anyway. So, Yellow, can you… can you dive into that?

Exactly. So yeah, perfect. These are the elements that we typically then use, and what we want to share today with the audience is sort of the blueprint That we use on projects with our clients, how we set it up. So, first of all, what we want to discuss today is then the example of a hard file that I already slightly introduced in previous slides. Right, so this, these heart valves is a… First of all, what we want to do is determine the suitability of the intent, purpose, and the indications, right? So what you need to do there is determine, okay, what's the clinical background of, of all of this? What are the clinical conditions and indications? So we're talking here about people with heart disease, obviously, so this could be heart failure, or valve disease.

How sick are these patients? What are they, what is their life expectancies? That kind of things. describe here what are the treatment options. So this could be, indeed, the implantable heart valve, and maybe it's also surgery, or just pharmaceuticals. And what are the claims of those treatments, right? similar devices, so what are competitors doing? But also, what are the claims of those competitors, and what are they saying about their device? This is very important for you. As said, you need to earn your place in the market, so this is the threshold that you need to reach. Medical societies here can be very important. These societies publish, as you know, clinical guidelines. What are they saying?

And that's more from the clinical perspective, but it can also be technical product standards. If you have a device type that's been on the market for a long time, there's a good chance there's a product standard saying, maybe, what kind of material should use, or maybe what kind of strengths it should have, what kind of… all sorts of things. So that would be the first thing to, to, To address, and put on paper. But secondly, also then, what will your device be doing? So the clinical performance and the clinical benefit. describe the relevant elements of your design, as I said. So, maybe here you see sort of a 9mm dressing, is that important? Or you might want to

Do it different than your competitors and have a different type of material that's maybe more beneficial to your device, design. what are the medical effects? Well, of course, you're going to restore here the heart… the blood pressures, the flow, and whatnot. Yeah. But on the other hand, as said, you also need to say something about safety. So, what are known for simple side effects? Certainly for heart falls, lots and lots of clinical investigation are out there. So do a literature review. You're probably going to learn something about written disorders, bleedings, infection rates, that kind of stuff.

This teaches you what are the side effects, and also what rate of side effects is probably acceptable, at least currently, right? Because that's what you need to know. If 10% affection rate is reported. You cannot come along with 15 or 20% defection rate. This is something that you need to know. If you know all that, I was already getting ahead of myself a little bit. If you know your clinical performance and your risks, you can go into the clinical outcome parameters. These will help then, as I just said about the infection rates, but also maybe how much the blood pressure can be improved, or your life expectancy, how much can be improved.

All these kind of things. And finally, then, also mention the alternative treatments. You need to say something about alternative treatments. We see these comments coming back from the notified bodies, so how does it relate? If you have a good alternative in your pharmaceuticals or different surgical options, why would you bring a more risky device to market? Right? You need to explain that, if you can, or you don't have… maybe you don't have a place on the market. Yeah, so if you take all these concepts together, then essentially, that's what we do, what we then do, they have checkmarked all four of those main elements that we just said, right? So you determined, okay, my device indeed is suited for the… has a suitable intended purpose, right? This is the way physicians,

use this device. You say something about your clinical benefits, but also your risks, and this is then your basis for the benefit-risk ratio, how to determine it. I want to pause here, indeed.

You know, this is nice for, you know, for Valve. You know, there's a lot of data there, out there for fails, but how about we take a different example? How about we talk about purchase?

How about, how am I going to do that for a crutch? Yeah, I think that's an important comment indeed. The MDR tends to be a little bit more easily to interpret for Class 3 devices, when all these difficult terms can be addressed and maybe easily answered. if you are indeed gonna talk about crutches, I think you can still be, use the same terminology, fill the same boxes as we highlighted here, but you have to be a little bit more pragmatic, right? So, sure, you can explain the clinical background, People need crutches, I think that can be easy to address. Clinic conditions, yeah, that's going to be a wide range of clinical conditions. It can be just a temporary broken bone. Maybe it's more of a chronic disease. Medical societies can be very helpful here, maybe even insurance… insurance companies, right?

Yeah, clinical performance, yeah, you can, you know, be supported by something. I always skip over product standards, that can be very important here. well, safety profile, maybe for such a simple device, you're quickly done. So yeah, all in all, I think you can still take this blueprint, but you have to be a little bit more pragmatic, but you can still fill it, and hopefully, it will be actually helpful. in, Succeeding in making a nice clinical evaluation in the end.

Yeah, so again, here, the SOTA, the gathering of the SOTA data, or being able to perform an analysis of SOTA and all these different elements in early phases of development really helps you towards ensuring that your device will be able to To have its place on the market, and be accepted also on the market. So if we go one slide further, Yella, I think, No, actually, I don't any… yeah, I don't any comments on this?

Yeah.

Yeah, would the people in the audience comment on this?

Or does this help? Maybe problems you fusion?

Yeah, I see a goalie, goalie is raising her hand.

thank you, thank you, Robert, and We, see… I'm also consulting for med tech startups, and I see breakthrough devices. U.S, pretty straightforward, like, you have guidelines and how it is, handled, especially for clinical data. In Europe, I find some challenges, especially with state-of-the-art. So how do you handle breakthrough devices or noble technologies?

Yeah, that's a very good question, thank you very much. So, in principle, it starts with the same basis, because, Also, in the US, if you have a breakthrough device, you need to meet certain requirements. It's not like, oh, yeah, it's a beautiful, new, great, it's all breakthrough. Well, you know, if you really analyze it, it's not… it is not. So, first of all, you need to define What is it breaking through from? Okay, that sounds a little bit weird, but it means where do you move away from? Or what are you going to do differently? But to be able to do that, to quantify that, to define that, you need to establish what is now the currently accepted way of working, or the currently accepted way of treatment, or analysis, or diagnosis, or whatever.

And from there, you can start building your storyboard. And that is exactly what is now happening in Europe behind the scenes. They're working on a MDCG guidance document first, about a… an additional or more clarification on how breakthrough devices in Europe Can be handled, and also the process around it involving expert panels slash notified bodies in earlier phases. To ensure that, this, this, these devices do. go to market, based on, you know, the evidence needed. So, but it all starts with being able to explain what the current, the situation is. And then…

Identify what is unique in this new device, either by technology, or by type of indications that are being treated, or by the whole patient management going in a different direction. So those… you can't do… you can't do breakthrough device, in my opinion, without having a well and sound Analysis of the, of the soda for these, for the devices that, that you are… you're, you're trying to put on the market. And also, they… in the future, there might be, instead of only having a guidance day, there might be some more changes towards, Towards these type of, processes inside of the MDR, but that's, you know, future. We don't know. That's the crystal ball.

That's what we keep asking, to everybody. So, I see Sean have a question?

Yeah, I just wanted to point out that Maria Donowa posted an article this week about similar devices under NPR.

I'm putting the link in the chat. Yeah, very good, yeah, we saw that too, thank you. And that's actually… the similar devices are a set of devices that you are going to compare yourself with under this soda. But it's not all, because you also need to be able to assess, for example, if your device is moving into patient management, you might need to look into other types of treatments, like what Yel indicates, medicinal Treatments or other devices, totally different approaches, etc, etc. So, similar is really about, okay, this is what I know, but we think you need to be a little bit wider, or you… actually, the NDR indicates that you need to be a little bit wider, so make sure that you do not forget that you only focus on similar. You need to be a little bit wider in your scoping of SOTA.

And then you address all the other elements that are required with anyone. But it's also good… it makes good business sense to know what you're comparing yourself with, and that helps in the end, and then we make a nice shift towards the next slide. I see…

Tracy, sorry, or Stephanie wants to be a panelist. Sean, can you maybe add her as a panelist? I guess she has a question. I didn't seem to have that option.

I'm sorry, repeat, please.

Stephanie is in the chat asking to be a panelist.

I'll promote her. Thank you.

Curious if she has a question. Or comment.

Okay, I've promoted her. Shh, take a second. Stephanie, are you with us?

Oh, yeah.

I just… sorry.

I just wanted to make a comment on this state of the art.

I actually have a… I'm a… I'm a consultant.

for those of you that don't know me, I actually, this whole state-of-the-art argument, I have a real big problem with it, because.

My reviewer is very, very junior, and she considers it as best of the best. And we haven't convinced her otherwise. And the problem with this is that the device is very, very innovative. And so there's no comparison. It's actually sort of a new way of clinically managing, so I'm actually prefer… you know, when we're talking about state-of-the-art, that we revert to with really innovative technologies, or technologies that handle or manage new clinical conditions, or new clinical method of clinical management, I would really prefer that we would be allowed to use the terminology is that this medical device brings some clinical relevance. In other words.

either the safety of the procedures improve, for example, or the effectiveness of the treatment improves, or, you know, I have.

already, Stephanie.

Banging your head against the wall on this one.

It's definitely already what the… you are comparing yourself with something. And your wording that you're using, I know, but…

with something. So you need to know what you're preparing against, and then… Yes, of course. Now the processes are being, behind the scenes, they're working on a process.

to… that allows you to argue exactly what you are now saying. And it's not necessarily the state of the art, it's really about breakthrough compared to what is state-of-the-art, and what are criteria, and how that process can be handled. So I fully concur with you, and if you have a… I apparently have an assessor of a customer with a notified body that is junior, or that.

That's a different day.

Yeah, that's a different discussion. I would call up somebody else within the notified body that you have known from before, but that's just a personal opinion there, and that's now on camera forever. Okay, Thank you. So if we, if we dive into the next, session, which is the, the long… Sorry.

I see a hand raised by, hopefully, Pete, or Biette, I hope…

So, I was in the Q&A, Fox, and there is someone anonymously asking, do we need to look at all Data from all similar devices for a device. If you can also check the Q&A box.

I had actually that had exactly that problem with the reviewer, is that she wanted us to compare all data from all devices.

But that wasn't for me, this comment. No, but it's a very, useful comment, actually. Yelli, any thoughts on this?

Well, what I did with one client in the past was… There was a long list of similar devices, but in essence, maybe there were 2, 3, 4 main competitors holding, let's say, 75-80% of the market, something like that. So what I argued was actually, well, if I just investigate these 3-4 devices. I don't have the bulk of what's clinical… what are the clinical benefits, the clinical performance, but also, maybe more important, what are the clinical risks? What are the foreseeable side effects? And with that, I said, I argued, okay, well, let's generally acknowledge what we already spoke about. This is my landscape, I can compare it with only these four. And in the end, that was accepted. So, yeah, maybe it takes a little bit of back and forth, but I think it was a fair argument, a fair rationale.

Thank you.

Yeah, that would be one solution. Robert, what do you think?

No, but I think it's a very fair question. Of course, it's not doable to do everything, but… and also, we had some discussions also with other people, and also internally, you know, do we need to do a full literature search already to determine soda? Yeah. Yeah, well, that's an interesting question, of course, and we saw some of that coming back in a certain clinical evaluation standard that's currently under development. So, yeah, the… what… the practical approach here is what is indicated. Are you leaving out potentially, information from devices that are not identified as the big three, in the example that, yes, the other side. Yeah, yeah, yeah, there are. There's this risk.

And, yeah, what can you do on it? Not a lot, but you need to build a good storyboard, and, if you can really say, okay, this is how we are going to… to handle that, that, yeah, that should make sense, so, Tracy?

Hi, yeah, sorry, apologies, because I did, join late, I may have missed it, but, I can kind of… I think probably I'd just, add some more comment, and just, I suppose, some example, or some weight to what you've already said, just from my experience. So I, was contracting with Abbott for… 5 years. Through the… well, essentially from 2020 through to the end of last year, and actually led the team that, submitted over 50. technical files for IBDs in the infectious disease area that were approved, and another 20 that were still going through as I left. So, substantial, amount of experience of,

well, it felt like hundreds of reviewers, I don't think it was quite that many, but there were certainly quite a few, file reviews that went on for more than two years, and had multiple reviewers on them. So we had the challenge of, of, having to work through that. quite often with different kind of takes on things. We took, I think probably a kind of best-in-class, because Abbott was an early adopter, so we started, obviously. Well, Abbott started before I joined, but we were already submitting files from 2020, and so took a best-in-class approach to SOTA, kind of actually dedicating, I'd say, probably a month's work just to that one report as a sub-part of the clinical

This report. And actually, in doing so, we were never questioned on the methodology or the actual content of it, because it was given so much time. And I think, crucially, what we learned, was that it was… in an IVDR submission, which I appreciate is probably Evan's more MDR here, but, I expect it should be the same Really, in the majority of cases, it is about storytelling, and it's about the linkages. So, if you… you have to know what your story is across your submission in its entirety before you start to do your state of the art, although your state of the art needs to be done at the beginning. You have to, therefore consider

And select based on what you're going to do, in terms of what you're going to show for your risk management, what you're going to show in your clinical performance in terms of reference, product, devices you used, et cetera, et cetera. You have to show that woven, and stemming from the state-of-the-art assessment. So, you know, it's kind of… we, for example, always had a section on, clinical guidelines. We always had a section, you know, that was a literature review. We actually had the issue where our devices were… well-established technology in some respects, like HIV devices, or on the other hand, devices that were, in the end, you know, novel when they came through as COVID flu.

For example, in the midst of the pandemic. So, but I think it, you know, if you… if you set out knowing what you are trying to achieve, what that core message is. Whether it's well-established technology, or it's a novel, and it's better equal to. Etc. And in a lot of cases, these devices were long established, and certainly. not of the latest, technology even, and we should… we did not shy away from that. We… we very much alluded, and we actually spoke through robustly what was available in terms of all different technology. But ultimately, coming back to the fact that, the lateral flow device as it was had a, you know, a very clear place in the diagnostic pathways.

Therefore, because it's still part of that, that it still has its place.

Absolutely, so I think…

of the art, so, yeah, thank you very much. feedback, Tracy. Carrie, I see you also are holding up your hand. I do have one last item I'd like to go through, but, Kerry, I can… we can answer your question first. Yeah, I'd just like to go quick, too. I had probably one of the first,

technical files declared in the EU for medical device, and the reviewers are very… Young when it comes to it, and they argue it. And so, as long as you're… very clear, the EUMDR 2017 uses state-of-the-art multiple times, but it doesn't define it. For example, in Annex 1 on general safety and performances, but it does not provide a formal definition, and so when the reviewers kind of come at you, as long as you, you know. Hold your ground with it, and clearly… define it. I only had 5 questions come back from the formal reviewers on my first one. Medical Device Coordination Group also explicitly listed along with it, again, but it doesn't formally define it in the MDR. Iso 14971-2019 definition adopts it by the regulators and the notified by.

one, yeah.

Clause 328 of ISO 14971. 2019 defined state of the art as developing the stage of current technical capability and or accepting clinical practice in regard to products, processes, and patient management. Based on relevant consolidation, finding science, technology, and experience. And a note adds that the state of art embodies what's currently and generally accepted as good practice. It does not necessarily imply the most technologically advanced solutions. And I dare you to challenge your reviewers with that, again. It's clinical. It's your clinical.

And so that's… that's what we… we try to, bring across during the first part of the presentation, really. Yeah, be sure that, exactly those type of discussions are very, openly, you know, done, that you take the opportunity with the notified body to have that discussion. But we also experienced, and probably you too, Kerry, and other people here, that while the years were going on, the consensus and the understanding got a little bit better on on state-of-the-art and the… and how the storyboards can be written. So, yeah, we can see on all sides that they are… they are learning. Still, they are hiring new ones, like Stephanie indicated.

Okay.

And you have to go through the struggle again. So we can only hope that in the near future, there, this will be also on the agenda of notified bodies to get a little bit better aligned. And maybe there's people listening in.

You have there on your slides.

Yeah. Okay, so, yeah, like, let's go to the last section. If everybody's okay with that, because we haven't talked about the claims yet, but the claims, actually, we did talk about, because we, by now, if we've done the SOCA analysis, we also know what is happening in this field that we are targeting, and we know what the other similar… Alternative devices are doing, actually. And, so you can, you can actually learn also there what claims are out there. They can be clinical claims, they can be technical claims, all sorts of types of claims are out there. And what we find is that, ensuring that you know what's being claimed helps you also

to talk internally with them cowboys from marketing. Because the cowboys from marketing, they are always, always talking about, that your device is the most brilliant one, or your IVD is performing most effectively, etc, etc. So… Then, if you come back with a question, so, and what does that mean, and can you quantify it, then they start stuttering, and we need to find a solution for that. So, in the view of SOTA, can we implement claim assessment also there, and later on, of course, claim management, because whatever we can prove is what we can prove, and not all the other things that might come out of the pipeline of them cowboys from marketing.

So… Make sure that the claims that the marketing or the business really wants to be a part of your devices are being assessed also on, first of all, feasibility, but also on how does that relate to what is out there in the market. Okay? And of course, there's a… we wrote down here a couple of examples, and there's a lot of ways, eventually, to prove and support these claims. And although there, for example, in the MDR, it doesn't say, specifically something on claims other than you cannot do, you cannot make claims that cannot be substantiated. But in our opinion, it is something that is an integral part of your development anyway, because it's real life. Make sure that you use those claims and that you make sure that you have the evidence to support them, because, again, the notified bodies do look at it

From different angles, actually, during your initial assessment, but also later on when they come back for an audit. Next slide, please. So… If you look very carefully, somewhere here you can find state of the art. We tried our very limited and probably deficient way of presenting what some of the processes are that are being activated once you go to design and development, or actually also before that. And, the state of the art is something that is happening, should be happening, early phases, and preferably even before, initiated before the design and development, so that there's a good storyboard also for the design, group to work on.

And translate that into the required design inputs. And eventually, these devices will go to the market, you will get your clearance. I heard two years or more. It is actually improving, although the numbers don't show it, because the numbers that the European cognitive authorities are publishing are not looking into, is it getting better? It's just still the, all the way back in from the past, unfortunately. But it is getting better. Experiences are that there is more responsiveness, there's more cape. In some notified bodies, people are actually waiting for work, so let's stop them with our dashes. So, if we go to the next slide, you can also see in the post-market phases, state-of-the-art isn't ending, because one of the… you know, you will be stupid as a company if you are not looking into what your competitors are doing, what they are placing on the market, how those devices are performing.

Of course, your own device also, but how do you relate to these new devices coming into the market? Can you still make that benefit-risk evaluation ratio, claim, whatever we're going to call it? So you need to also include in your activities, your methods that are forming your post-market surveillance. you need to put in something there on how are we going to assess what is happening in the market. What is now the state of the art compared to when we looked at it last time? Maybe the last time was the first time? And how is it going to evolve? Because there's a lot of new technology coming out, and we have been talking so far only on…

on hardware, on IDDs, but there's also software and AI And things are basically exploding on that side. So we need to be very aware that the SOTA never, ever stops. It's an integral part, and it drives your PMS, and the rest of these processes are then again driven by the input coming out of PMS. Yeah, I think, we have one more slide, right?

Yeah, the takeaway.

Yeah, summarizing slide, I think, yeah. Oh, messages, yes, that's also a nice way to say it, okay? So, state-of-the-art. It's not, again, not necessarily the most technologically advanced solution. As also indicated by Carrie, just now and by Tracy. It is really what is currently and generally accepted as good practice in technology and medicine, but then specifically for your group or device itself. Okay, so that you are in control there, you determine what you want to fit in, where do you want to fit in, and that's your storyboard, basically. So, how to do it, how to structure it, that depends on you, but please take into consideration

Those, elements that we just showed you on the… in one of the slides that Yellow presented.

That really can help you to make sure that you have touched on all the different elements that.

not only the Notify body asks you to be aware about, but also your business might be… your business might be very much interested in. Yeah, so again, the depth, the detail, it can differ. It definitely fits within clinical, it definitely fits in risk management, but it also drives the development of technology and the use. Claim management, same thing here. It is a… in the way that we see it, it should be part of your SOTA assessment while you're investigating the market, and you see what your competitors are doing. See how they make claims, and how you can make them measurable, and whateverness you have available.

Yeah, I think this is, sort of summarizing from our perspective, SOTA and how it integrates in different processes, but also is driven by, business, business obligations and business expectations. And, looking forward to hear from you guys if there are any remaining questions left.

I saw one comment, Robert. Oh, sorry.

Okay.

compete, and I think it's also that the source of state-of-the-art standards was ISO, I-A-C-E-N, and simply put, I fully agree with it. It was also in the first text box, and you can use these documents as well.

Okay, okay, yeah, very good, thank you, BF. And I see somebody waving. Oh, that's show.

So, my question is, you know, I've heard the term fit for purpose tossed around, and I'm wondering if there's any relationship, or if there's any definition of that term, and if so, how that relates to state-of-the-art.

I have some thoughts on that, but I'm not sure whether there's a formal definition in any of the regulations. Maybe the room here can help us out, but the fit for purpose is very much linked, of course, to… in essence, in the wording already, although not being trained on English, you know, by native language, but it feels the same. I know it's emotions, it's regulations, don't do emotions, but, fit for purpose really is, okay, what are you going to do with it, on your device itself? But the state of the art might be a little bit bigger, meaning, okay, and what is the rest of the world doing with these type of devices? Or not the world, but the actual users, so…

Maybe somebody else has some thoughts on this? Fit for purpose?

I think that sounds right.

Yeah, oh, okay, good.

I… if I just, I think Fitbit for Purpose, for me, sort of matches more instruments And clinical relevant outcomes would be, you know, more of the device side. I don't know. It's just, I guess, a thing of wording. I just like… I really like the… wording of just saying, you know, it's clinically relevant outcomes, you know, in terms of safety, effectiveness, or performance. I prefer that much to the state-of-the-art, because I've been… I mean. We have ongoing discussions now for 2 years, and this revere just doesn't let go. It's like a dog's holding onto the pant leg at the bottom. And it's just driving me crazy, I have to tell you. And, I mean, I've heard all the other things, but if you have a junior reviewer, and she's very convinced of herself, you just can't get rid of the dog biting your pet leg. Sorry.

I may want to comment on that. I mean, that's our regulatory people's biggest challenge. People not understanding, or does not have an openness to understand your technology. What has worked for me is, not the conflict. So, the sooner you neutralize the conflict, sooner you make them realize that you understand them, it's like the tension kind of drops. So it's more of a mental game with them than the actual performance data that you need to convince them with. Just my two cents.

Yeah, we… I mean, I've… I've worked with lots of reviewers, but this is… this is the toughest one. And it's going… it's gone so far to… to the point that she's recommending to us which tables she wants to see and have.

Hmm.

I mean, we've escalated… We've escalated it. We've escalated it, and the escalation response, we've never gotten one. Okay. Within the notified body, so…

You're older.

I would name the… I would name the… yeah, I would name the notified body. So, BSI, actually, the escalation did not go well for us, one of my clients. Reviewer actually complained against the company to say they have not treated her well. And BSI supported their own reviewer, not the company. So I personally feel it… the energy doesn't need to be escalated like that, it just, like, doesn't go anywhere once it got escalated.

And again, if you… I've had a similar statement. these type of comments coming back from another body, and you see, and you feel, okay, they're not understanding, they're… I don't know if you've done… probably you've done it, Stephanie, but this structured dialogue, you can also… it's nice wording, but in the end, it means sitting down, either electronically or in person, and talk through this and come up with a proposal. and make sure that your proposal makes sense, and see if you can then come to a concession where not only that review is there, but typically there's also the expert involved that can… that, you know, you can have some discussion there. But again, it is the.

I agree with you.

difficult, yeah.

I… thank you, Robert, for mentioning that. We… we have. And the problem is that she has a very set way in which she wants to have it. But she doesn't tell us, so then word comes to words, she can't consult. But she has a very set way in her head on how she wants to have it, and we haven't figured out what exactly is her set way that she really wants to have it. And, yeah, and… and it's, it's.

It's very difficult.

I've been… anyways, it's a human factor to this, yeah?

Yeah, yeah. Thank you. Sean, do we do one last question from Anoush, and then wrap up?

Yeah, that's fine.

I don't have a question, just a comment.

Oh, okay.

You have reviewers or auditors that don't serve the purpose. Actually, there are two steps. You can try to educate them on your innovative device. That's what I've done on medical devices that are one of its kind, like an implant, an active neuroimplant that makes blunt people see again. You don't find multiple bodies aware of how to, to consult how to approve such a device. On the other hand. If you find that they're capable of going along, you can educate them, and you can build this together to make it actually a viable medical device for the market, and improve quality of life for plant patients.

And that's… that's what it is about.

You'll find that the notified body is not good enough. then you actually have to change it. That is what I've done in the past. There's switched notification body, and you can have different modified bodies, one for quality management, the other for, actually approval of medical devices. So, I'm sure you're aware of that, and that's the way to go along. If you… if that, young, auditor or reviewer that you are actually having trouble with is not doing the job right, you have to change that person. Yeah.

I think it's a… I think it's very fair, what you're saying, Anoush, but I also want to be… a little bit supportive here, because we don't… we should not only complain about things that do not go right, because a lot of things are going right with not everybody, so we need to, you know, we need to give Mosul some credit here, and the ones that do not go right, of course, take out, because that's as usual with these type of things. So, Yeah, again, if we… if we… I think we all need each other, and it's all for the best… you know, patient care eventually. And that's also something they are definitely realizing, but that they, you know, they are also under pressure from their authorities. If they, for example, miss out on certain elements that are… they get scrutinized or hammered later, then they might lose part of their designation, or all of it.

And that's also not in the best interest of ours, so we need to be… Supportive alike, Anish, what you're saying, we… we actually educate them along, and that's… if you have a unique technology, that's what you need to do anyway, and that's why SOTA soda is their comfort zone. They should know their soda. I don't know if you ever read Annex 7 in detail, but it actually says, not in these type of work, but they also need to be aware of so that they need to know what's the type of devices that are out there, and how they're performing. It's part of their obligations, too. So, if you touch on that… if you touch on that one, then it really would help to build your story, as Carrie indicated, for example, so…

Sure.

Right?

Scene, Sean.

Yes.

I just put it in the post chat, what you need to do to satisfy what they're asking for. If you answer those, use those. You'll be fine, and then… They'll go away.

I love all the collaboration, all the input.

Next. Sorry.

Carrie, thank you for providing a detailed explanation in writing. It's… .

That seems slow.

Yeah, I think that we need to wrap things up.

We can do another discussion later.

I want… I mean, that's one of the things I love about this call, is that… is that it is an opportunity to be collaborative, to build a story together, and, Let's see… Carrie, it starts with notified bodies when they use the phrase fit for purpose, or what… No, you said you posted it below. Provide the following, and they're satisfied. It didn't show, so…

It didn't show… so it's up above. Notified bodies, so there's… they want to see what, For FITR purpose, they mean the evidence package for the technical documentation, risk management, clinical evaluation, and PMS data.

Okay, I'm gonna post it to everyone.

Are you going to put it up so they can all see it? That's what they want to see.

Okay, well, we can follow up with this. I want to thank everybody for their time, as always. I want to thank the speakers, Robert and Yella, for, their patience on the flub, still working on transferring to a different platform, but, you know. Time takes time. I'm gonna be reporting live from Rome next week, exciting, as I'm gonna have a roundup at the end of Team PRRC, what… what we learned, what the key takeaways are, and we're gonna have, two very special guests from CREATE, a regulatory consulting group that's developing AI, to help, assist people with. regulatory affairs people with their… with their work. I met them at RAPS.

They're very interesting to talk to. I just had a call with them. I'm excited about that, and I think… that the following Friday, the speaker is Michelle Wu from Nyquist AI, which is coming at this problem, from a very, very different, perspective more in terms of global regulatory tracking, and what's interesting about Nyquist is they have access to China and Japan data that other people don't have. So, if you're interested in, global regulatory, follow that. I have a number of, new projects, new opportunities coming up. There are 3 webinars before the end of the month. Next week, there's gonna be,

a nice investor thing, from Lean Rocka on the 23rd, 22nd, 23rd. I posted that in the chat. Then there's going to be EIFU with Accra Team, and after that, this very, very cool new program that we started, which is matching 5-day email courses with webinars. So, the, clinical program that we're doing with Donna Well Life Science, what you need to know to initiate pre-market clinical trials in the EU. on the… whatever date that is, the 29th, the 30th, I can't remember. You're also gonna get,

enrolled in an email course, which comes over 5 days, so it takes the curriculum from the webinar, expands it, and provides more detail. So this is an interesting new thing. And then the last thing I wanted to leave you with Is that for, 2026, and this is… this is, you know, stealth mode here. MedTech Leading Voice Exchange is launching a monthly country-specific, like, 360-degree view of the med tech market in Ireland or Italy or the Netherlands. And it's going to be an excellent opportunity to involve people with in-country expertise, to get a full picture of what's going on.

You know? What's going on in Italy?

Right now, you know, in terms of clinical.

in, terms of startups, in terms of what's the market like? You know, what does contract manufacturing look like? What does distribution look like? How does it work? I want to go do business in Italy, how am I gonna do it? Right? And I think that, provides an interesting opportunity for more collaboration, more input, more speakers. So I encourage you to keep that in mind, and reach out to me if you would like to be. Involved in the planning of any of these, or have any recommendations for which countries we start with. Because you know I'm starting with Italy, right? I mean, you know me, and you know that my ultimate goal in life is to retire to a villa in Italy.

Somewhere.

in the near future. So, there we go. Thank you all. Thank you, Robert. Thank you, Yella. You're welcome. Thank you, everyone who contributed and who is here. Which is a contribution in and of itself. Remember that. You've already done a great thing today. Please help us spread the word. Feel free to contact me directly with speaker recommendations, or… Other comments? Anyone who had trouble getting in today, I apologize. I, again, hope to get all my technical problems solved in the near future, and I thank you all. Cheers.

Welcome.

Thank you.

Happy weekend.

Thanks. Bye.

Bye-bye.