ISO/DIS 18969: A Process-Based Approach to Clinical Evaluation (What It Changes)

3… Hello and welcome. My name is Sean Smith. Today, I am very excited to introduce, so the name of the webinar is ISODIS 18969, Introducing a Process-Based Approach to clinical evaluation, featuring Danielle Giraud, CEO of MD Clinicals. and chair of the ISO 18969 Working Group, and Maria E. Donowa, MD, founder and president of Donowa Life Science, member of the ISO 18969 Working Group. It's amazing to have, two of the authors, two of the conveners of this ISO standard coming in.

Maria E. Donawa, MD: I mean… One convener.

Sorry. Amazing to have the opportunity to get an inside look at the making of the standard as it's being developed. Here are a few housekeeping notes from me. One, important. Recording and slides will be available to all registrants. They'll be sent tomorrow, 24 hours following the event, by Zoom. 2. Certificate of Attendance. If you would like a Certificate of attendance, it is available upon request. Please write your name as you would like it to appear on the certificate, and your email address in the chat, not the QA, the chat. Right? Use the QA function to ask speaker questions. So, if you have questions about the standard, put them in, or for the speakers, put them in the Q&A function. That's important. There will be a brief poll following the first presentation and a post-survey webinar. Please, please share your feedback. It's important to us. It helps us provide you with better things in the future.

If you're interested in learning about speaking opportunities in 26, 2026, email me, I'll put my email in the chat. What's coming up? This Friday, something very, very special. We're gonna be announcing the MLV100 for 2026, that's the 100 people worth following on LinkedIn, and we're introducing a brand new AI-powered platform. which allows you to ask expert questions and get expert answers. I'm gonna put the link in for that as well. Next week, Global Human Factors Strategy for MedTech. This is amazing. This is gonna be EU versus US versus UK and China. we're adding China to the list. So, join us for that.

And also, for e-regulatory Roadmap Part 2, Avoiding Liability and Pitfalls. So I'm gonna put all the links in, and with that, I'm turning it over to Danielle. Danielle, it's all you. Thanks.

Thank you, Sean. Thanks for the invitation and allowing us to speak. Maria is just saying one convener, because she's always afraid I'm going to ask her to do more. So, I'm going to share my screen, and let's get going here. So, do you see the full screen?

Yes.

Yes, I think you do. Okay. So, I'll just need to… Oh, something was in the way. So, we talked today about 18969, a very hot topic. I mean, I've been in standardization since many, many, many years. But the 18969, I think, contributed to, a few… too many, gray hairs. It was, rocky, rocky roads. To get where we are now. So, a bit about myself, I've been in the medical device industry over 30 years, it's actually close to 40 years, and I've been leading the Technic TC194 Working Group for, since 2008.

Mainly initially for 14155, and then since 3-4 years, the 18969 baby was added to our list of things to do. So that's what we're going to talk today about. That was just a short intro. So… you need to be aware that this standard is a draft international standard, which means we are waiting for the comments to come in March, and they will probably influence still a lot of its consent, sorry. But what is important to understand is what we're going to talk about today is the philosophy behind 18969, which, in my view. It's pretty important to understand and to take home.

So, I always start with this, a little bit, I'm a bad drawer on, on, on slides, so this is really homemade. The next one is much better. When do you actually start with clinical evaluation? And, a lot of people think that clinical evaluation under the European regulatory process, at least, is this evil mandatory documents that you need to write right at the end, when you don't have time anymore, and you need to do them quickly. And… That's not what our document is, is about. Our document is, the 18969 is not about document writing, but really about a process.

So it really… that process really starts very early on in the design and development phase, with the design planning. So we came up with this nice little… let me put… because I can't see it fully… with this nice, drawing that was actually… I gave a very ugly drawing to a designer, and he came up with something, like. this. So, we think in our standard that there are a lot of people that should work together from the beginning, and that includes the clinical evaluation. There's a lot of… input that clinical evaluation can get early on to be prepared for later activities, but there's also a lot of input clinical evaluation can give into design and development, into risk management, regulatory, and other functions. So…

you will see there's a lot of dotted lines with a lot of, repeated activities. It's… for us, it's a process. It's something that is… over time evolves, matures, and becomes, obviously more firmly determined. In the beginning, and that's what I'm going to repeat in this presentation a lot, in the beginning, it's a collaboration. It's a collaboration for risk management to have the full input from clinical about what what is needed. Also. Design and development can give already some early inputs about what is the intended use, what do we think the risks may be, what do we think clinical performance may be. But it's an ongoing process, and the process is even enlarged once we know enough about the device, and the device is ready for human use.

to be used in clinical investigations. That's that blue part at the bottom. So, this is a little bit what this process, wants to, to, to demonstrate. It's… this… this graph, or this image, wants to demonstrate, is it's an integrated process that starts early on, and then… You will not have those Mandatory, evil, necessary documents at the end, because you will be prepared throughout the process. So… We… In the standard, to make it easy, and to also look at it a little bit from a process, and how the process evolves.

We've kind of, come up with these four, development phases, early development, mid-development, late development, and then the post-market phase. And each of the phases, clinical evaluation can, we've worked out what clinical evaluation can contribute, what happens during these phases. So, in the early development phase, we talk about defining the therapeutic needs and the clinical sex. There are potential patient populations. We don't know yet. They may reduce, they may enlarge, they may… we need to see this early development. Possible indications for use. The intended clinical benefit, or you've developed the device for something, so you must have an idea what it will deliver as benefits to patients.

What are these current medical and non-medical alternatives, so that you justify why you designed this new device? also relevant evaluation criteria. So. The purpose there is really establish a solid clinical rationale for developing the device at this early phase, and that's where the collaboration between design and development and clinical evaluation, or the clinical team, can be very optimal. The mid-development, we start knowing more and more about the device, whereby, do we… what do we know already? Do we know things from other products, from other, what we call medical and non-medical alternatives?

And start planning. How are we going to generate the evidence? When the device is ready to be used on human beings. And then in the late development, meaning, really, we have kind of a frozen design of the device. We know a lot of the device. We really are going to… we are generating this clinical evidence. On a specific patient population, with specific claims that were developed with specific intrications, contraindications, and so on. So, we really want to document that clinical evidence to ensure readiness for market release, and plan, then, the post-market surveillance activities. And then the last phase is the post-market phase, where we continue to look to work with design development where needed, with risk management where needed, with the regulatory people, and so on, and we do the clinical part of the activities. So these are more or less these four phases that we…

Take as a baseline, a backbone of how the process evolves over the product lifecycle. So, I'm talking about this input, a little word here. The input from design and development, making the middle part a little bit bigger, is, providing clinical… the clinical team with intended use, potential risks, clinical performance, clinical benefits, and user requirements. And then, in the… in a really integrated process, the early clinical evaluation planning starts. Whether you do that with your… I'm talking about a process, I'm not talking about a document, but you could

already start populating your end documents, your clinical evaluation plan and clinical evaluation report, if you want to talk that way under MDR terminology. to start documenting these things. Obviously, you're gonna have many versions, because by the time you get to the final version, you… there will be many iterations, because design and development has iterations, risk management needs input. from the clinical team on what type of risks are documented already with other medical and non-medical alternatives. So. We really, in our standard, we emphasize on a strong cross-functional team collaboration, linking process of clinical evaluation with design development, clinical development, risk management, regulatory strategy, and later post-market surveillance.

And now, you may say… some people on… listening in, they may say, we do that already, which is good. But I think Maria can also confirm in her presentation that many don't. And that's where people work in silos, and that's where things get ambiguous, inconsistent in the documentation, and where, at the end, there are the clinical evaluation people who only get, like, a couple of weeks to write that clinical evaluation report, because they haven't started on anything earlier. They haven't worked… they were not worked into the whole process. That's important. So this slide kind of depicts a little bit of a longer list of inter-process input and the input back from the clinical evaluation. So, it's an ongoing process. This is not, like, a one-go.

Not everything will be ready at once to give to clinical evaluation, and clinical evaluation may not find everything neither, because they will do some searches in the literature, or searches in available knowledge, any sources, and they may come up with some things that prompts new questions from design and development or risk management, and so on and so on. It's important to look at that as an ongoing process of collaboration. So, open the doors and the windows and stop working in silos. So, during the planning, a little bit more of information here. Iso 18969 leaves open to manufacturers how to document things, but specifies what to document.

So, we're not going to make a mandatory template of a CEPCR, everybody has their template already, but we have a list of things in an annex that we say, this needs to be documented in way or another. Now, we have a lot of pressures from people who are MDR brainwashed, let me say it that way, that's saying, we should talk about a CEP and a CER. Well, my perspective is like that, and I have lived through that with some elements of 14155 as well. Even though regulations say a certain thing, when you start really looking at it from a process-oriented thing, and believe me, we have notified bodies on our working group that say, yeah, there's a point here. We may get better information, better documents.

If we look at it as an integrated process. They are a bit like, yes, but MDR says planning a report. Well, fine, but our process doesn't interfere with these documents, really, because you can still document certain things in plan… in a plan and in a report. So, during the early stages, several iterations of the searches in the literature, but also in other available sources, may be performed. They may not require the rigor of the appraisal, like we say, you need to do it before you just finalize your document and make really a final clinical evidence. So, sometimes there are questions that we try to answer by looking

at available information that don't need all the rigor. So this is also, again, a little bit where we want to balance the things. And we don't want to overburden. One of our missions was try to keep it simple. but integrated. Facts such as conferring applicable GSPRs, final claims, quantifications of these claims may be completed over time while the product design is being set. So, if you want to document all these activities and all these findings in a clinical evaluation plan, you'll be prepared just to have updates of it while the document becomes mature. Work with versions, and include also early drawings that then correspond to your findings, so you know why you found this data in the literature that may not be any more applicable in a later design, so you may then run your search in a different way.

The analysis of data from available medical and non-medical authors may not be subject to all requirements, neither that are part of a formal pre-CE mark planning document. And because in the planning, we are really working on the available information on the claims and so on. what we call SOTA now, and you may have realized that I haven't used the word SOTA yet, because we're trying to minimize, we're trying to work really with available knowledge. But what we call now the SOTA analysis, or available medical and non-medical alternatives, may actually become more Part of the plan. than the report.

I mean, I would say, who cares? Notified bodies will go like, hey, but we need an analysis, and so it can be done whenever it is ready, and if it's part of the planning, because, you know, this chicken and the egg, where we need to quantify in the planning our claims. But we need to do the SOTA analysis in the report. That's also what we're trying to solve here a little bit. So, guidance is provided on sources, considerations for medical and non-medical alternatives, and then, I'm just… we have some special considerations on transferability of clinical data. we are not using the term equivalence. This is a regulatory term for us, we're in the process. We just say there are regulations that may allow you to transfer data from one device to another.

And then go to these regulations, and we give the links to the regulations, but we're not a regulatory document. And then we also have special considerations for certain types of devices, and that in the draft, in my personal, humble opinion, we still need to work it out a little bit better. where we just say, okay, SAMD, including AI, may need special considerations, but we don't say what they are. So, I think in… between the DIS and the FDIS, the final draft, those are areas that we need to work on a little bit better, and also on these other products. We also have some conditions allowing limited types of data when there is no interaction with patients, and so on. It's quietly briefly, but to really… I think it…

It may come out with less… with not that much precision, because we want a document to come out, and then mature over time, and we'll get feedback. We've done like that with the 14155 as well. The most important thing is that we have that process-oriented document that comes out as quickly as possible. And then. as I said before, with a true integrated process where the analysis of available medical and non-medical alternatives has been conducted in an early design phase, like acceptance criteria are defined in the CEP articles substantiating accepted criteria, and so on. It may well be that the whole SOTA analysis becomes part of your planning, because you need

to go into that SOTA, to into these available metrics, to be able to substantiate already how you're going to position your device within all that. So… Let's, let's see how we can make this as clear as possible. What we have done, you need to know the way this document has been written was trying to put the MDR aside. But to think about the process. So that this process is not only useful for the MDR, but also useful to start a clinical investigation, which FDA is looking at quite a lot, and even Japan is looking at it quite a lot. It can be useful at so many opportunities. It can be useful input to risk management, so we get more meaningful information out of the risk management document as clinical people.

That's also a mission that I still need to work on with the 14971. We are… it's firm in our plans to start discussing, put our heads together with that group. So, that integration is really important, and I promise not to talk too long, but to leave time for questions, so I think this is my last slide, and then I'm handing it over to Maria. Before we go into questions. Stop sharing. There we go.

So, I've gone ahead and, posted the poll, question. It's just 3 questions, so please answer that so that we have some feedback. Maria, feel free to minimize it on your screen, and talk over it.

Maria E. Donawa, MD: Okay.

And it will run for a couple minutes. Reminder, if you want a certificate of attendance, please write your name and email address into the chat, and we will provide that. Please be patient with us. It takes us a couple days. We do these manually. But if you don't get it by, you know, sometime next week, let me know. That's all I'm gonna say. Maria, it's all you.

Maria E. Donawa, MD: Oh, yes, it's a pleasure to, to actually have this opportunity and to actually share time with Danielle on, on this subject. I'm gonna… Maria E. Donawa, MD: Before I get into my presentation, I'm just gonna say something that, Maria E. Donawa, MD: And I don't know if those of you who are evaluators who actually do clinical, evaluation reports, I've not always been a fan of this, process, and Maria E. Donawa, MD: I won't get into more of that now, but when the effort of 18969 started, I wasn't a fan of that either. There was a lot of work put into how this could be useful. I mean, there were people who thought that the process of clinical evaluation could be useful in general, not just as it's done in Europe.

Maria E. Donawa, MD: and evolved into the process of clinical evaluation. And that's when I… Maria E. Donawa, MD: thought, oh, yeah, okay, I… fine. Until that happened, I… I was not, I was not happy. So now I see really, very nice potential for the practical use of this. So with that, I want to get started. So I'm going to be talking about Maria E. Donawa, MD: some of the ways this could actually work, how you would incorporate, clinical evaluation or deal with it in terms of existing standards. So the 13485 Quality Management System. Maria E. Donawa, MD: 14971, which Danielle mentioned, of course, risk management, and also regulatory strategy.

Maria E. Donawa, MD: Just about me… oh dear, 40 years. Maria E. Donawa, MD: Scary. U.s. and EU regulatory experience, I deal just with those two regions. I'm a stakeholder member in the EU MDCG, group that develops clinical evaluation and, Maria E. Donawa, MD: clinical investigation guidance, and have the pleasure of being a member of ISOTC194, working group for a very long time, working with Danielle and seeing how amazing, she works with these, Maria E. Donawa, MD: herding cats and dealing with complicated issues. And then, of course, I've been an evaluator of clinical evaluation plans and reports for over 20 years, another yikes moment.

Maria E. Donawa, MD: So… I wanna… what I'd like to do is, Maria E. Donawa, MD: Danielle mentioned the MDR and the need to kind of Maria E. Donawa, MD: keep that in mind, but we have, in clinical evaluation, very good working knowledge of what that means in Europe. So even though we're working on an international standard, and the idea is to go through valuable processes that could work for anyone, anywhere. Maria E. Donawa, MD: we do have a practice, a set of data and experiences based on Europe, and Europe, of course, as you know, most people know, Maria E. Donawa, MD: has very, very strict requirements for clinical evaluation. So, yes, the MDR specifies very stringent requirements. What's really happening? And again, Danielle made a point about this. What's really happening is

Maria E. Donawa, MD: Clinical evaluation is addressed very, very late in the design and development, process, and at that point. Maria E. Donawa, MD: when they are… when it's being dealt with, it's very late in the process. So, it's, then the other issue is that, and these are just miscellaneous, Maria E. Donawa, MD: issues that arise. Clinical data to support marketing claims. You know, companies consider marketing claims, clinical marketing claims, sometimes very important. Maria E. Donawa, MD: And very often, they're treated as an afterthought. They're not even addressed early in the design and development, or they're not addressed in a systematic way when you are developing your clinical study documentation.

Maria E. Donawa, MD: Now, we know that risk management teams perform a very… very rigorous and strenuous work and very detailed work. Maria E. Donawa, MD: But as, again, was pointed out by Danielle, they don't always have the clinical input that is later going to avoid problems with regulatory scrutiny. Maria E. Donawa, MD: And, and then the regulatory strategy, and I'm going to touch on this briefly, is not always… Maria E. Donawa, MD: consistent with, or in line with how, clinical data are generated, with clinical evaluation requirements, and… Maria E. Donawa, MD: They're very separate activities, and they're not coordinated.

Maria E. Donawa, MD: So… The potential value of this standard Maria E. Donawa, MD: Is, again, it provides a process Maria E. Donawa, MD: And there… and if you are talking about the… and I'm not talking about, post-market, I'm talking about Maria E. Donawa, MD: mostly pre-market, or the first time that you are developing, designing and developing a device. So, in terms of design and development and risk management and regulatory strategy, the idea is to have a process, that deals with this, in a, in a… Maria E. Donawa, MD: deals with these issues in an organized manner, so how can… how can we do that?

Maria E. Donawa, MD: We have tools, so again, and I'm thinking about 10 different things while I'm speaking, so bear with me. But in terms of actually using the 18969, Maria E. Donawa, MD: standard. Maria E. Donawa, MD: 969 standard, we have tools. We have the, quality management system standard, 1345 on the left. Maria E. Donawa, MD: And we have a guide, and hopefully many of you have experienced or have used the guide, which can provide more detailed information than has been included in the standard. Maria E. Donawa, MD: So I'm just gonna go through certain parts of the design and development planning, activities, or design and development stages, or phases, and just make certain points about, how these can be useful in terms of clinical evaluation. So.

Maria E. Donawa, MD: Those of you who are familiar with the design and development, process know that, the planning stage Maria E. Donawa, MD: is critical. It's… you don't just launch into design and development. You really need to plan it carefully, you need to document it carefully. It's a very important part of the reg… of the standard, and it's not always… Maria E. Donawa, MD: done in a way that, should be done, but it's critical. So you have… you define your stages, and then, you… another important element is that you… Maria E. Donawa, MD: define the reviews that you are going to… and these are meetings, they could be in person, they could be remote, whatever. Meetings of the design and development, people who were involved in that process

Maria E. Donawa, MD: And the idea of the review is to, Maria E. Donawa, MD: evaluate each stage of the design and development. Then, of course, you have verification, validation, and design transfer. You need to talk about what you're going to do. Again, this is planning all of these activities. Maria E. Donawa, MD: The responsibilities and authorities are critical, who's going to do what and how, and also the… if you… outputs to inputs traceability is, how are you going to do that? Because you're going to have a lot of requirements, those are the inputs, and they have to relate to the outputs, or…

Maria E. Donawa, MD: They're going in different directions, and of course, the resources that are needed now. Maria E. Donawa, MD: This is where it's interesting to think, let's involve clinical Maria E. Donawa, MD: expertise, or clinical evaluation expertise, and if it's the same person, fine. If they're different people, the ideal situation is that you have people involved at this stage, early on, with what you're going to have to deal with later on. And again, we're talking about the regulatory world. Maria E. Donawa, MD: Where, design and development is heavily regulated. Maria E. Donawa, MD: The other place where you can identify clinical evaluation, or where it is useful and productive to do that is when you are defining your resources.

Maria E. Donawa, MD: the necessary competence of personnel. So again, during the planning phase, if you're in an ideal world, this is when you're talking about that, and you are… and you are including these people at that point. Maria E. Donawa, MD: Now, design and development inputs, is a… input's another word for requirements. Maria E. Donawa, MD: This is another critical stage in design and development. This is where you are… you… to be effective, you are considering all of the various elements Maria E. Donawa, MD: that are involved in the design and development process. So clearly, you're gonna have to cover these areas. So, functional, performance, usability, safety requirements, absolutely.

Maria E. Donawa, MD: This is the area that is addressed, but not always. Maria E. Donawa, MD: Effectively. Maria E. Donawa, MD: In your, requirements of design and development, in your inputs. Maria E. Donawa, MD: the regulatory requirements and standards. I get the feeling that companies don't always anticipate where they're going to market their device. Maria E. Donawa, MD: It seems like something that would ought to be automatic, but sometimes it's not. If you're initially going to be in Europe, fine, but if you're thinking about the US, it would be a good idea to at least have that in mind.

Maria E. Donawa, MD: Now, this is another element Risk management, the results, the output of risk management. Maria E. Donawa, MD: is a design input. What you end up deciding Maria E. Donawa, MD: which are the requirements, or you identify risk, and how you can… how you ver… how you, reduce risks, and how you introduce risk control, measures, all of that, the output of your risk management program becomes Maria E. Donawa, MD: A requirement of design and development. Maria E. Donawa, MD: It seems counterintuitive, but… Maria E. Donawa, MD: that's what happens. Risk management feeds into your design, and you need to pay attention to those elements that you've, that you have identified as risks, and make sure that your device design is designed with those in mind, or trying to reduce as much as possible.

Maria E. Donawa, MD: You might have information from previous designs. Maria E. Donawa, MD: And, and of course, there are other, other requirements. Now. Maria E. Donawa, MD: This is a critical element for clinical evaluation. I've highlighted performance and safety requirements. Of course, many clinical evaluation Maria E. Donawa, MD: reports include usability, but for the purposes of this discussion, I'm just highlighting, those two, performance and safety. Maria E. Donawa, MD: And, again, the outputs of risk management. So, we're talking about how, the standard 18969, can be, Maria E. Donawa, MD: Useful in the process.

Maria E. Donawa, MD: Process of arriving at the information that you need to, develop. Maria E. Donawa, MD: So… Clinical evaluation expertise can really support just about all of these, of inputs. Maria E. Donawa, MD: And when I say clinical evaluation expertise. Maria E. Donawa, MD: I'm not talking about clinical expertise. Clinical expertise is absolutely valuable. As I said before, if you have it in the same person or group of people, you have both clinical expertise and clinical evaluation expertise, all the better. Maria E. Donawa, MD: So, the… another, critical, Maria E. Donawa, MD: a critical aspect of design and development is the design and review process. This is when you…

Maria E. Donawa, MD: examine, and you define what the stages are, but you examine the stages where you're going to get everybody together, and I mentioned this before, to look at whether or not Maria E. Donawa, MD: The requirements, or the activities of a particular stage, have been followed, and the requirements of that stage have been met. Maria E. Donawa, MD: You are going to… and this is… Maria E. Donawa, MD: as you can imagine, simplifying this greatly. Identify any actions that need to be taken, and, participants need to, and the standard specifies this, participants need to include representatives of various functions, but certainly the functions

Maria E. Donawa, MD: Concerned with the design and development stage, the particular stage that's being discussed. Maria E. Donawa, MD: and other specialist personnel. Now, a lot of you may know that FDA Maria E. Donawa, MD: forever, had, required that someone independent of design be involved with design reviews. Since the adoption of, 13485, that specific requirement is not in, is no longer a part of the FDA requirements, but it makes sense Maria E. Donawa, MD: In this discussion, to consider that the other specialist personnel who may not be involved in the actual design would be clinical and or clinical

Maria E. Donawa, MD: Preferably, and clinical support with clinical and clinical evaluation expertise. Maria E. Donawa, MD: This is… the stage where… I was gonna say the rubber hits the road. Maria E. Donawa, MD: I said it. This is where… Maria E. Donawa, MD: the validation activity, is intended to demonstrate that the device meets its requirements. So. Maria E. Donawa, MD: This is specifically talking about, Maria E. Donawa, MD: design validation. Design validation can, include a number of activities to show that the device is meeting its requirements, and, I'm not… Maria E. Donawa, MD: It's tempting to get into a discussion of, design verification, but in… what we're talking about here, is…

Maria E. Donawa, MD: the validation… clinical studies, if you are going to need to conduct clinical studies, it's a part of design validation. It's done when you've done all of the other work that's been necessary, to do beforehand, and Maria E. Donawa, MD: just pointing out something in the standard. The standard, 13485, mentions clinical evaluations or performance evaluations in the case of IVDs. So it states that clinical evaluations or performance evaluations must comply with applicable regulatory requirements. That's a small statement, it's a big meaning. Maria E. Donawa, MD: It's speaking, however, generically. It's not referring to what we are facing in Europe as clinical evaluation or performance evaluation.

Maria E. Donawa, MD: So, the point, Maria E. Donawa, MD: that I wanted to make here is that the design validation process is where, or in terms of clinical studies, it's the stage where you are showing that the device meets its, meets the requirements that are, consistent with its intended use. Maria E. Donawa, MD: So, just… Maria E. Donawa, MD: Pretty briefly, the other critical part, and again, we're talking about how to make the, the activity of 18969 Maria E. Donawa, MD: practical and useful. Now, again, we've got the tools already. We're anxious for the standard to be completed, but it's,

Maria E. Donawa, MD: already, there are things that we can do that are useful, so… Maria E. Donawa, MD: The Risk Management Standard, 14971, most of you are familiar with that. Hopefully, most of you are also familiar with the guidance document 24971, which has significant information that can be useful that is not in the standard itself. Maria E. Donawa, MD: So, I'm just gonna make… there's a… there's a particular, point Maria E. Donawa, MD: the purposes of time, that I want to make, it's, kind of a personal, Maria E. Donawa, MD: I'm not sure how to describe it. Maria E. Donawa, MD: the… Maria E. Donawa, MD: it… Danielle emphasized the fact that there is benefit to have people work together, to have clinical expertise, to have risk management expertise, work together.

Maria E. Donawa, MD: I'm just gonna give you one… Example of something that Maria E. Donawa, MD: happens, and you may see it as well. Those of you who, who, develop clinical evaluation plans and reports. Maria E. Donawa, MD: A key element of the risk management process are these matrices, these tables, the risk analysis, whatever you call them. Maria E. Donawa, MD: They list, they're like, you can't have a document that's more important than risk, as far as I'm concerned. They're listing the hazards. And I'm listing these things on the left-hand side. The sequence of events that can lead to hazardous situations. If you do not have a hazardous situation, you don't have any harm. So all of this information is critical. Then you have the severity and probability of that harm.

Maria E. Donawa, MD: Before you… Maria E. Donawa, MD: have defined your risk control measure, something you're going to do to reduce… it's hard to eliminate a risk, but something that's going to reduce it to an acceptable level. Maria E. Donawa, MD: And then you have the risk control measures themselves. And most companies, they may… they document those. It's gonna be, it's gonna be an animal study, it's gonna be a bench test, it's going to be, information in the IFU, all kinds of things to try to reduce the risk, and… Maria E. Donawa, MD: Those are documented in risk control, in the risk control

Maria E. Donawa, MD: Usually columns of these, these tables. Maria E. Donawa, MD: And then you have severity. Again, that doesn't usually change. Maria E. Donawa, MD: It's always the same severity of a harm. And the probability After the risk control measures. Maria E. Donawa, MD: I didn't list all of the elements of the table, but what you do also have, and what… you've now introduced all these risk control measures, that's not enough. You have to verify that they have been effective. Maria E. Donawa, MD: You can't just say, oh, you know, I'm gonna include something in an IFU, or I'm going to do a dog study, or I'm gonna…

Maria E. Donawa, MD: You have to show that they've been effective. Maria E. Donawa, MD: I cannot tell you how many risk tables I've seen. Maria E. Donawa, MD: Where clinical studies have been conducted. Maria E. Donawa, MD: And they are not indicated as a method to verify the effectiveness of a risk control method. This is a regulatory issue. If clinical studies have been conducted for a particular… and they have, to show that the device works and is safe. Maria E. Donawa, MD: From a risk point of view, you really need to indicate where that clinical data applies to a particular, risk. Maria E. Donawa, MD: And then the last point, ensuring that all risks have been adequately addressed is a critical component of the clinical evaluation process. Very small statement, very important, very critical. It's one of the

Maria E. Donawa, MD: The areas that, one would spend, one of the most, most time is spent in clinical evaluation looking at safety and the information that is backing up that safety. Maria E. Donawa, MD: In terms of regulatory strategy, and I've put in EU and FDA, because again, we're now… this whole… Maria E. Donawa, MD: Discussion is about a standard, an international standard. Maria E. Donawa, MD: But… and by the way, I might have said it clearly at the beginning, I'm not sure, that the standard makes the point that you really do need to, consider regulatory strategy. So, the importance of 1345 in terms of,

Maria E. Donawa, MD: Design controls, and in terms of risk, fine. But regulatory strategy is key, clearly, because Maria E. Donawa, MD: Again, when you are launching a new product, And, Maria E. Donawa, MD: you go to all the trouble to do that, and then you find out that you've not met the regulations is tragic. So the regulatory strategy needs to be aligned with the clinical data requirements. A tiny little statement, very simple statement. Maria E. Donawa, MD: But it very often is not done. We know instinctively we have to do a clinical… we have to, conduct a clinical study. Maria E. Donawa, MD: what are the regulatory implications? That's not always examined properly. And again, the standard is to help us to be much more formal in all of that… in that activity. Clinical investigations

Maria E. Donawa, MD: Are definitely not always planned. Maria E. Donawa, MD: Considering the regulatory expectations for all kinds of reasons. Maria E. Donawa, MD: That would be very interesting to get into, like, investors and pressure and timelines. Maria E. Donawa, MD: This is… the third point, though, is something that, is very interesting. Maria E. Donawa, MD: The MedDev guidance document for clinical evaluation that was developed Maria E. Donawa, MD: For under the directives, and is still used Maria E. Donawa, MD: for the MDR, as long as you make sure that you're complying with the MDR and not the directives.

Maria E. Donawa, MD: Still includes very interesting and useful information, and one of them is your clinical data, if you're going… if it's going to be important, and not just, you know, it's, you know, additional information, but if it really is important. Maria E. Donawa, MD: and you are basing your CE marking, or your, Maria E. Donawa, MD: even the U.S. clearance or entering the market there. Methodological quality and scientific validity Maria E. Donawa, MD: are elements, and they're long lists… not… I shouldn't say long, they're fine. The lists that are… of activities and considerations that go into the… deciding the methodological quality

Maria E. Donawa, MD: And whether your data are valid. Maria E. Donawa, MD: Determine whether the data are going to be acceptable from a regulatory point of view, and very often is not looked at Maria E. Donawa, MD: As an activity. Maria E. Donawa, MD: And this is… and where I see this, and where I have to look at this, it's when somebody says, here is all the device information, please conduct, please develop the clinical evaluation plan, which is funny, and report. Maria E. Donawa, MD: And then, that's when the methodological quality and scientific validity is looked at. At that stage, it's something that Danielle mentioned before. It's too late. So, 18969 supports

Maria E. Donawa, MD: the alignment of generating, clinical data with sensible regulatory strategy, again, not specific, rigid, oh, let me… okay, let me cross the rigid part out, even though I mean it, but… Maria E. Donawa, MD: With the regulatory strategy, we have to meet the regulations. So, I'm just gonna end this, I almost want to call it a tirade, but I hope it's not taken that way. So what can we do now? We're waiting for the… the… Maria E. Donawa, MD: 18969 to be, Maria E. Donawa, MD: to be in final form, hopefully to evolve to the point where it's a published standard. But in the meantime, there's certain things we can do. We can involve clinical and clinical evaluation expertise in the design and development process now. That's what

Maria E. Donawa, MD: I mentioned earlier, that's what Danielle mentioned. Maria E. Donawa, MD: I didn't spend a lot of time on methodological, quality and scientific validity, but Maria E. Donawa, MD: You can do that now, and the sooner you do it, the better, and it would be lovely to do it as you are developing your clinical study, protocol. Maria E. Donawa, MD: Early in the process, not… you've done the data, and now you have to retrofit what you've done into having some type of validity. Maria E. Donawa, MD: Clearly, it would be very helpful if the risk management documentation identified where clinical data, were actually used to verify risk control measures. And…

Maria E. Donawa, MD: The final, activity would be to, don't forget… Maria E. Donawa, MD: about marketing claims. Think about them early on. Maria E. Donawa, MD: And try to include them so that they are substantiated by data and not left out, so that you have to actually eliminate a marketing claim. Maria E. Donawa, MD: With that, I'm going to, that's, that's, that's, that's it for me, and hopefully we have time for questions.

I think we have, and we do have questions, so… I'm gonna start with the easy ones. Sorry, I'm not following the exact order, but when can we expect the standard to be approved? The standard, I… we have to finish… well, I have… I have the, the mission of, finishing all the comments that we will receive in March to integrate them and to come out with a final draft international standard by the 17th of August. It's a very specific date that is according to the ISO rules and so on. once… for those of you who are not familiar, once an FDIS is published, very little can still be changed afterwards. So, hopefully, if we're done with the FDIS and we send it to ISO, they take usually another 6 to 8 weeks to…

edit it and do some things about it, so I guess sometime around October. F this. And… meaning then, yes, people can make editorial comments, but no longer technical comments. But it's an ongoing work, so even if we bring out a document in October, we'll probably have to kick in and continue to work on it, but we'll just bring out a document that is already useful.

Maria E. Donawa, MD: Danielle, yeah, when you finish, let me know.

Yeah, I'm finished. We have other, questions.

Maria E. Donawa, MD: There's one that I'd like to do, take, and that is, how likely is it that the United States will adopt.

Oh, no.

Maria E. Donawa, MD: this ISO. You might have seen this. It'll be a tremendous burden to manufacturers to have to create CERs for U.S.-only devices. Maria E. Donawa, MD: So, let me just briefly say something, and then Danielle, please. So, first of all, Maria E. Donawa, MD: At this point, FDA does not require the clinical evaluation process or documentation that's required in, in, Maria E. Donawa, MD: In Europe, and so a lot of what I felt, initially about clinical evaluation was really colored by that. You know, FDA doesn't need it. The requirements, FDA and U.S. requirements, are, Maria E. Donawa, MD: they're very often known, and the system is so different than in Europe, and then you have FDA, who… the personnel who've developed a lot of expertise. You can go to pre-sub, and you can do all of that.

Maria E. Donawa, MD: I now believe that because companies do not always go to the to the U.S. prepared. Maria E. Donawa, MD: They don't always go systematically understanding what a good clinical design means and how risks are reduced. That there is a potential Maria E. Donawa, MD: To use the approach… That is, being described and developed in 18969 Even for the U.S, Maria E. Donawa, MD: there are… there are a fair number of companies that get turned back from the U.S. and from the proposals of their clinical study designs. So, there is value, but in terms of FDA actually adopting the ISO, or the… Danielle, you may want to speak to that.

Well… I… this is where I… I saw 18969 is not a regulatory document. It's a guidance that describes a process. Perfect. And that doesn't mean that all of a sudden, because 18969, even if FDA approves this, because they have given already quite a lot of input. Lately, we've lost our FDA member, but I'm not going to get into that battle. But even if FDA approves the document. That doesn't mean that their regulations are gonna change. We are not looking to change regulations. We're just saying, at a process, make it useful. Make it a useful, collaboration between risk management and 13485. That doesn't mean make it mandatory, or…

hey, FDA, change your regulations. No, this process is useful for many other things, not only for MDR. So that's what I would say. No, I don't think so.

Maria E. Donawa, MD: Yeah, agreed.

And then there is, the question, is CE often late because engineers are trying to develop a product first, and then they have something workable? Only then do they spend the expense of clinical evaluation. Well… I think the comment, again, looks at it from a point of view of, we need those documents. But the clinical evaluation, as I tried to explain in my presentation, is not the whole process all the time. It is a collaborative effort. that if… R&D and risk management is helped by clinical, the process can be more useful and more effective and productive.

So, I don't see if at all 18969 is trying to make it more efficient. Rather than… But if you look at it, of course, from an MBR perspective, saying, well, we need those two documents at the end, then yeah, R&D will always wait until they have a full developed product, or will be tempted to wait. But large companies that have a full, a good process in place, integrated process in place, they do already, they apply already what 18969 is trying to achieve. I don't know, you want to add something, Maria? cycle, Odyssey on the cluster.

Maria E. Donawa, MD: I was just looking through the questions, there was one, Maria E. Donawa, MD: Yeah, I feel like this draft ISO is, geared towards higher-risk devices, those that require clinical investigation. Maria E. Donawa, MD: device line extensions for lower-class devices need a much more simple, less involved process. Fine, but, too often, even for low… lower-class devices, the… Maria E. Donawa, MD: Even for those devices, the level of risk, the level of data that you need, even if it's, it's all about understanding the level of, data that you need. Maria E. Donawa, MD: Information and data to feel secure about safety and,

Maria E. Donawa, MD: And performance, or, Maria E. Donawa, MD: Effectiveness, which is a term used in the U.S. Maria E. Donawa, MD: And… if we can… if the standard can be developed to the degree that I hope it can be. Maria E. Donawa, MD: It's just a way of not waiting until the end Maria E. Donawa, MD: To look at safety and performance elements. Maria E. Donawa, MD: ad hoc, or not at all, or not enough, and to get people involved. Having clinical expertise can indicate that you don't have a Maria E. Donawa, MD: a risk where you thought you had one. It can give you a much more accurate set of, or it can give you much more accurate information than if you don't have that expertise, or if someone is,

Maria E. Donawa, MD: Basing a decision on, you know, what they think, or maybe on an article that may or may not be interpreted correctly. Maria E. Donawa, MD: So, it… Maria E. Donawa, MD: if this… if the process works, properly, and if the standard can… can end up to be where I hope it can be, it's giving companies, Maria E. Donawa, MD: I want to be careful about how I'm describing this. It's a system to… it's a way to function in an organized manner with the people who should be involved, so that you avoid Maria E. Donawa, MD: Wasting time, wasting money, everybody's concerned about efficiency and getting things done in an efficient manner, and what I see most often is when decisions have been made

Maria E. Donawa, MD: This thing is plopped in your lap, and… Maria E. Donawa, MD: people who could be useful in avoiding problems with safety and performance have not been involved in the process. It's a very, very common situation.

We have another one, If you already comply with the MDR requirements, does ISO 18969 add any requirements? No. We are just laying out the process. MDR is not laying out the process. MDR is asking for information, but they don't necessarily lay out the process. So, it is not our intention to add requirements, it's just our intention to clarify the process for those companies where it's not in place. I think that's… and then by incorporating the new search in early planning phase, do you mean that literature search protocols to be outlined? This is exactly what I was trying to say. These early searches don't necessarily need the rigor that you would apply when you do your searches, really, for the end, evidence, that you want to give.

But I strongly suggest that it's a little bit… how complicated do you want to make it? But I strongly suggest that you work in a systematic manner, that if you do a search, that you at least document a little bit what the subject of your search was, what were your keywords? Because if you don't come up with the right output, you at least know, you can go back and see, what did I do wrong? So, it's more a practical thing than anything mandatory that you're trying to make. But the early ones, indeed, are less strict and less formal. But it's always good to document what you've done, and what the basis of your searches were.

So, anything else that I can find? Maybe time for one more? Question… The concept of CR is already part of Japan and China. Yeah. Well… I… again, I see the question here. The concept is already part of the Japan, and not… I think not that much of Japan, but definitely China. Because we have a hard time getting our Japanese friends on board with our standard. They are actually afraid that Japan is now going to try and implement, like the question here about US FDA. we're not in… we really don't want to interfere with the regulations. We… again, I repeat it again, over and over, we really want to map out the process so that people can work better together, and we can come in better documentation of clinical evidence.

Thank you. We're about out of time, and so I want to thank all of the attendees. I want to thank the speakers, I want to remind everybody of the upcoming events. Again, if you, want a certificate, please put your name and email address in the chat. Please answer the, survey, that's gonna pop up on your screen when you close this. Maria, Danielle, any closing words as we sign off? Thank you both very much.

Well, there's still a lot to come, so we need to work further on the documents. I hope we can make it as useful as possible, and please give it a chance. It's going to be a work in progress, you know, process as we get input and people learn to work with it.

Maria E. Donawa, MD: Yeah, I think that's perfect. It's just supposed to make sense. It's supposed to help. It's not supposed to add a layer of unnecessary work. There is some discipline to it, but it… Maria E. Donawa, MD: the… if it's done correctly, then there's gonna be the payoff of knowing what you're doing instead of just, winging it. So… Maria E. Donawa, MD: Yeah, and if there are questions that were not answered, feel free to send me an email.

Okay, well, thank you all.

Thank you, everyone, for your time and attention. As I mentioned earlier, the, recording and slides will be sent tomorrow, approximately 24 hours after the event, via the same Zoom email that you registered with. So, thank you again. I hope everybody has a wonderful day or evening, and I look forward to seeing you again soon. Thank you.

Thanks, Shel.

Maria E. Donawa, MD: Everybody.

Thank you.