Ask the Experts What You Need to Know About MDCG 2022-21 - Guidance on Periodic Safety Update Report (PSUR)

Hello and welcome everybody to what you need to know about MDCG 2022-21 Guidance on Periodic Safety Update Report, PSUR. In other words, what your parents never told you about PSUR. I'm very pleased to be here today and would like to thank everybody on behalf of the sponsor, Human AI, and hand it over to Basile. Before I do that, a quick housekeeping note. If you have questions, please feel free to submit them and I will make sure that the speakers are notified about the questions. And yeah, let's get started. Thank you, Sean, for the introduction. Ladies and gentlemen, good evening, good afternoon, good morning.

It doesn't matter where you are all over the globe. PSUR is relevant to all of us and we are here together to try to answer your questions regarding this new guidance related to requirements. So, the first requirement which was established was the publication of the IVDR and the MDR in 2017. Since then, everyone is asking what is actually the expectation? What does this article mean for me, for my daily work? And today, next to me, we have Marta Carignali from TÜV SÖYT Product Service GmbH, a notified body designated under MDR and IVDR. Tom Pattern, a notified body also designated, which is NSAI, which is N-S-A-I, which is N-S-A-I.

Tom Pattern, a notified body also designated, which is N-S-A-I, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I. Tom Pattern, a notified body also designated, which is N-S-A-I.

Tom Pattern, a notified body also designated, which is N-S-A-I. supporting also on IBD sector. Today, we're going to try to help you understanding the requirement, to help you understanding and guide you through the guidance document and share with you relevant updates. I think the speakers will give you also a bit of insight about themselves, and I will let them also introduce themselves in a bit more detail to give you more information about their knowledge and their background. So we'll start with Marta. Perhaps you can give some words about yourself and explain to us who you are, what you do daily in your organization.

Sure. Thank you, Brazil, for the introduction. And hello, everyone. Thank you for joining this webinar. My name is Marta Carnielli. As I said, I work for TÜV SÜD as a head of certification for in vitro diagnostic medical devices. I've been with TÜV SÜD for a few years now, but prior to joining TÜV SÜD, I was working for an in vitro diagnostic manufacturer. And I'm a I'm a I'm a spent quite some time in complaint handling, vigilance reporting, and post-market surveillance. And although with the IVD, the role published both pre-market and post-market phase of a device, this post-market surveillance topic is still near and dear to my heart.

Thank you, Marta. Tom? Hey, guys. Thanks for inviting me. First of all, to Sean and thanks for Basil, Marta and Robert for being on the panel with me. So my name is Tom Patton. I work for the NSAI based over in Ireland. My official title is certification and inspection officer, which basically means I perform conformities and activities for product reviewer and site auditor. My main responsibilities at the moment are designation under the IVDR, which is hopefully nearly there. And I'll be speaking today mainly around how this guidance is applicable to both medical devices and in vitro diagnostic devices. Before the NSAI, I was a

I worked in a variety of laboratories and a variety of IVD manufacturers. And in my current role in the Notified Body, I have responsibility for vigilance activities. So yeah, looking forward to the talk. Thank you, Tom. Robert? Yes, thanks, Basil and Sean, definitely for moderating this and for asking me to join this panel. Very happy to be here with DSAO Bioconsulting. The prime purpose here is to help developers and manufacturers of medical devices, in particular IVDs, be able to achieve compliance with various regulations, both certainly in Europe, as we're talking about today, as well as in the US. And the strongest connection I have in the

greatest utility is on the product development connections. So certainly anything to do with clinical evidence, but then also going into post-market surveillance and related areas is something that I... I help a number of organizations with. I, like others here, I have also been at developers and manufacturers, in particular of IVD products along the way. So quite a bit of experience in that and working with various regulatory agencies and bodies around the world. So thank you. Thank you, Rob, for your introduction as well. And last but not least, we have Sean Smith, who is actually hosting this event and supporting us getting action.

So Sean, I'm going to turn it over to you, Sean. Sure. Thank you, Rob. So I'm going to start with Sean Smith, who is actually the relevant, actually surrounding activities and a big thanks to him for doing that happen, making that realized and supporting us during the holistic process. My name is Basile Akra and I will be your moderator today and will be helping you through the holistic process and start with sharing a presentation. And I will allow Sean at the end as well to give you a bit more about how you can deal with these kinds of events. Share with us some insight. So I will start by giving us actually an update about where we stand in the European legislation.

What is the situation? And when I'm doing this, I will let Sean actually tell a bit more. And I'm just connecting actually my PowerPoint presentation. Sean, take over to my slides are actually activated and perhaps you can give me access to that as well. You have access now. Apologies. Hi, everyone. My name is Sean Smith. I am the founder of Illumina.co, a marketing agency. I'm a founder of Illumina.co, a marketing agency. I work with clients in the med tech sector, including Huma.ai, the sponsor of this event. Very pleased to be here. And on behalf of Huma.ai, I would like to extend a message that they're

offering demos of their post-market surveillance solution to anybody who either messages me during this call or sends an email to Misty at Huma.ai with a three day discount or an email to me. And I would like to remind you that you can get a demo of the product code that you would like to see a demo of. And they will do that for you. So that's a pretty exciting offer. I hope that you will take me up on it. And that's all I have to say. Thank you, Sean. Thank you for that. And now I would like to start, just remind us where we are, what happened to now. Give us a short update about what's happening in the EU.

We're now at the end of the session. We've had a few questions here from our listeners. So please use the chat to share with us your questions, if you have some. During my presentation, you might recognize that you have the topic or the other topic, which is key for you. And you want to get an answer from us. This is an opportunity to notified bodies, to experts and a person who has an overview, will be helping you actually understanding the requirement and making sure that they are implemented in your organization accordingly. It's something which was actually written in the initial publication of the regulation on MDR and IVDR.

And since then, a lot of efforts happened. I remember in 2018, it was the first MDCG guidance which was actually starting to be established. And this was actually after the publication of the regulation, people started working on that MDCG. They wanted to make it happen because of the importance and the importance for getting that clarified. It took so long. So four years of activities, one guidance document which was dropped and then reinitiated from scratch due to the Brexit because the leadership changed. And based on that, the holistic document need to restart. But now we are there. In December 2022, it was actually the month of the biggest surprises.

We got a lot of surprises. And funny, it was before Christmas. It felt like a lot of Christmas gifts coming on and a lot of things from a regulatory point of view, which are positive for all of us. So to start with my presentation, let me start with also an update about what's happening in the EU. And this is why I'm giving you this update, because it's important also with regard to PSUR. So as you know, since last mid of last year, a lot of discussion are happening regarding capacity, ability of the system to move forward, ability of the system to issue certification on time regarding notified bodies.

We still have a gap of notified bodies which are still in the EU. We are still in the designation process, especially for the medical device sector, but also for the IBD. The IBD is something where most of the people are not talking about it because they feel it is a long term project. And due to the additional time that people received, a lot of people push their project on a longer term. It's not recommended to do so, but people are doing that. Now with the MDR, we are heading towards actually a disaster. That's why last year discussion were happening at the European level to find the solution to the MDR.

the solution and i think for a lot of people the appsco meetings became actually very popular and famous and during those appsco meetings numbers were presented numbers were presented about realistic uh next steps and people recognize that it will not happen it will not be doable by may 2024 to get all the devices which were certified under the directive to move to the medical device regulation that's why we got all of this number in front of us which said that actually even if we we continue going and we get more notified bodies during this process we will not hit the target and the european healthcare system will be standing in may 2024 with limited capacity limited available

devices certified under the regulation which as you can assume not in the interest of the healthcare system and not in the interest of the patient this is why european legislator made a recommendation and this recommendation is now a proposal which was published in january 6 by the european commission to think about actually a new timeline for products which fulfill specific expectation of the mdr and specific expectation of showing that the manufacturer is doing all possible to move his device to the medical device regulation and based on that manufacturer might benefit from additional time till 2027 for class 3 and implantable devices and for to lower risk devices such as

2a core class 1 devices they will have an ability to move to 2028. now the point of discussion also which is key for uh for all of these activities they expect if you do that that you consider the post-market surveillance obligation also of the mdr to be able to benefit from this and this is where ps you are going to come into place and to roll into expectation as well the other additional point which is beneficial and i think this is not the topic of today but it's important for everyone is the sell-off period for ivdr and mdr which is proposed to be taken away as i said this is proposal i don't want to spend a lot of time i just

highlight how important it is to think about the post-market surveillance system because it will be also a guiding element for your derogation it will be a guiding element for the future proposal it will help you justify your ability to keep your device on the market where you are working towards mdr ivdr so make use of this make sure that you establish that and consider the expectation when they were valid to make sure that you are meeting the requirements if we look to the psur we got this guidance document which is actually referring to the mdr and talking about article 86 of the mdr but the requirement on psur are similar in both

legislations so we're talking about psur when we talk about ibdr we talk about mdr it's all about the same expectation we need to have data on the safety and performance of the device post approval and they're going to be summarized in post-market surveillance report and those post market surveillance reports are named psur for devices which are in a higher risk class and this is where everyone were was discussing about what is the expectation what is needed the article 86 of the mdr is nothing else than five six sentences which are talking about a psur but nothing is that section is actually explaining how to make it how to make it happen this is why we got actually the

guidance and the most important thing in that guidance is saying that it has to be a standalone document so it should be a document which is readable on itself which is focusing on actually safety signals from the market which is in the second article of the mdr but as i said we're ensuring that the manufacturer could summarize and come to a conclusion on the benefit-risk profile of the device to make sure that the device is still safe, still performing as intended, and there is no need for immediate reactions. So the post-market is not something new. It's something which was established under the directive and now with the new periodic safety

update report is much more systematic, it's much more active, it's much more defined based on clear timelines, which is risk-based, which you need to consider as manufacturer. And I think what is also important for us to remember what is written in Article 86, why we do all of these things, why it's important to do these kinds of PMCs, post-periodic safety update report. The periodic safety update report is nothing else than actually a report which is summarizing my evidence from the various documents. It's not a repetition of everything that I'm doing. It's actually building a report which is a summary of all my activities which are happening

in the various processes within my organization. This is very important. It's very important to consider and to remember that's all about your quality management system, which has to be compliant to be able to achieve the final target, which is delivering a periodic safety update report in line with the requirement. And then what is key and what is new is the way how you calculate your signals. In the past, a lot of manufacturers were calculating signals based on their sales. They say, I sold 1 million devices and I got two complaints. What they didn't consider is how many of these devices were really used in that period of time.

And they didn't consider how many of these devices were actually used in that period of time. And so they didn't consider how many devices were really used in that period of time. And this is a different way on how you're going to do calculation which you need to consider. And you're going to learn from the periodic safety update report guidance. I'm giving you all of that just to remember us what we are discussing today. Why is it important? The PSUR is in your requirement, which is valid for MDR certified devices, but it's also valid for implantable custom-made devices. It's also valid for IVD devices, which adds all valid for legacy devices. So there are a lot of obligations,

which can be applied to the following. So I'm going to talk about the PSUR requirement. you need to consider and you need to remember. So it's not just a new requirement for a new device. Don't forget Article 110 from the IVDR and Article 120 from the MDR talk about conditions enabling you to keep placing devices on the market. And part of these conditions, part of these prerequisites are to meet post-market surveillance and vigilance requirement of the legislations which are applicable for you. And part of that is also the PSUR expectation, which is expected to identify signal, expected to look into your CAPA, to your vigilance, and all of these activities

to conclude on what I said before with regard to this aspect, to conclude on benefit determination, to consider the main finding from a PMCF or for the IVDR from a PMPF activity to make sure at the end that your device is still safe and performing well. So what is the new guidance giving us? The new guidance is giving us templates, giving us information on how to do the activity, how to do the calculation, how to prepare the PSUR for a new MDR or IVDR certified device. It's not giving us IVDR directly, but I'm just saying that because at the end, you learn out of these guidance, how you can consider the legislation and implementation.

I think the panel will help us today understand, can I use it for the IVDR? Can I use it for the MDR? We're going to ask all of these questions. And I am pretty sure Marta, Tom, and Robert will help us understand how you can apply this guidance in the right way. This is all what I wanted to share. As a kickoff to make sure that we have actually a clarity about what we are talking about. So PSUR, periodic safety update report is the topic of discussion today. This is what we want to understand and discuss. And I will start by looking to Marta and say, Marta, I spoke about this guidance and I explained a bit about the fact that this guidance was created, was a focus on MDR.

Now, is it also applicable for other devices? I mentioned, in my presentation, IVDR might be also relevant. How do you see it? Which device is this actually, is this guidance considering and for whom is it? Thank you, Basil. So indeed, the scope of this guidance clearly references the MDR. It does not refer to the IVDR. However, we do expect that we will get it. So in terms of the guidance specific to the IVDR at this stage, still the requirements are fairly similar for PSUR between the two regulations. So my recommendation would be for IVD manufacturer to

review what are the, what is the guidance provided in the CGM document, and use it as a reference to the MDR. Thank you, Marta. Thank you. Thank you, Marta. Thank you, Marta. Thank you, Marta. Thank you, Marta. as a reference to build the PSUR also for IVDs, even though this guidance doesn't specifically reference the IVDR. One point related to this guidance is clearly targeted to manufacturers. Notified bodies are not in the scope of this guidance. And the review HTS notifies will do of PSUR, whether it is MPs or IDDR, it's not included in the specific guidance,

so it's really, really for manufacturers. Thank you, Marta, for this. This is actually challenging because actually it's an answer that is really, really important for the system as a whole to write it down. If we don't report this, then we are only doing it for the pilot, as a result, we don't know whether or beiries shovel will be reputed. if the notified bodies doesn't have like clear criteria, we might have a lot of deviation about how much they're going to be reviewing with regard to ZSB-SUR. But I think I'm pretty sure that notified bodies will discuss together how a harmonized approach will happen.

Like we saw recently from Team MB, a lot of publication on harmonized approach towards achieving better consistent way in the future. So looking to all of these situations, so Marta, you said it can be applied for IVD devices, even if it's not in this scope. So Robert, from your experience, would you recommend people following a guidance which is actually referring specifically to a regulation, which is a medical device one, or would you say, let's wait and hope that one day we're going to get one for the IVDRs? Well, very much along the lines of what Marta had said, the philosophy of how medical devices

and MDR, regulated devices versus IVDR regulated devices, his approach is very similar. So while it's probably inappropriate to make a strong reference that this should be the exact guidance, it is not, like Marta said. And so at some point in the future, we don't know when, there will be specific guidance for IVD devices under IVDR that help with the PSUR. It's quite likely that the overall structure and recommendations of what MDRs are, the PSURs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs, the MDRs,

the MDCG will be publishing, will not be so different. So it's good to use the information and it will be helpful, though it is not something that is formally a requirement for IVDs. Thank you, Robert. So Tom, if I'm a manufacturer in IVD, can I expect a notified body coming in and auditing me for my PSUR format and saying, you know what, you are not state of the art, the guidance is saying something else, you need to have more content or can I expect a notified body from a notified body? I mean, you are working for a notified body in this field and we see a lot of interpretation, but what would you say from a legal point

if you can notify body raised non-conformities or how can it be done? Basil, you asked two nice, easy questions for Marta and Robin. You asked me this. We need a scotch now. I do, I do. I'll start off with, as we are always told, all guidance documents, they're not legally binding. So as I work for a notified body and as I am an auditor, the first question that I always look for as a product reviewer or as a site auditor is, what's the requirement? And what's the requirement? And then what's the objective evidence from the manufacturer to support the requirement? Obviously, notified bodies have to take guidance documents

into consideration. And so I will look for evidence that the manufacturer has applied this guidance document, has a knowledge of it that is appropriate to their device. So it's kind of the same, the same format that we always, that we always kind of go for. In relation to the kind of the other, just to jump back to the previous question, the only other type of manufacturer that this guidance document may not be fully applicable to would be a class one manufacturer. But that's not to say that the class one manufacturers will also not get benefited using this device or this guidance. It will teach you

how to appropriate your data, how to analyze your data accurately, and then how to present the summary of it for your PSMR. I think it's what it's called. And for the PSUR as a manufacturer, Basil, your slides were excellent in that it's kind of the main point that I'd like to kind of hammer home. The manufacturer knows their device better than a notified body does. The manufacturer understands the data to support their device better than a notified body does. So as a notified body, what I would be looking for is an understanding of that data presented in such a way that is not a replication or a duplication

that you see in your PMS data or in your CER. We don't want to see that coming back in again. We want to see an analysis of that and a summary of it as per the requirements. So again, that's kind of what I would be looking for as an auditor. And again, I know we'll probably get into it as the questions come and as we kind of tease it out a little bit more. The difference between making available upon request or submitting for review, those two things. There's no, like from the requirements, you still have to, you still have to, you still have to compile a PSUR. One is submitted for review. One is made available upon request,

but the requirement is the same to generate one. So that's kind of how I would phrase that. So in summary, what I hear from you is actually something which is understandable, which is written also in the guidance. It says also, even for medical devices, the implementation of the guidance shall be considered in a timely manner, but manufacturer need to fulfill the requirement of the regulation. This is what the guidance is saying. So it's actually giving us a guidance towards actually a better structured way for the future, but it's not enforcing manufacturer immediately to implement it as long as they fulfill

what is written in Article 86, which are the three bullet points, which I mentioned to you that you have to fulfill and you have to have supportive evidence. But we need to ensure a consistent approach for the future for MDR and IVDR, and therefore you need to get guidance. Marta, can we expect a guidance on IVDR coming in the next few months? Can we expect a guidance on IVDR coming in the next few months? And if so, when do you think this will happen? We do expect that there will be either an addendum or a separate guidance specific to IVDR at a later date. So we don't know exactly when, hopefully not too far in the future,

but we don't have a date for now. Thank you, Marta. Robert, we got a question from the attendees saying, in the PSUR templates, there is written information from trend reporting. The data related to the trend report will be detailed after the adoption of the MDCG guidance on trend reporting. Does it mean that we are not obliged to add trend reporting data in our PSUR until specific guidance will be released? So the way the question's being asked, right? So the guidance is with effect or applicable immediately. As I understand it, you and others can kind of go into that. There is specific language in there

that if a PSUR has already been generated or actually is in the process of being generated, that there isn't a need now to kind of rework, certainly any documents that have been created or even in flight and being worked on. So I don't know if that answers that specific question well enough, right? So going forward, I think, I think, you know, I think that's a good question. I think that's a good question. I think that going forward the guidance should be considered for looking at any of the data that are generated and compiled for safety data and so forth. I don't know if that answers the question,

Basil, close enough to what was being asked about. Yeah, I think it's like, I mean, we are going in that direction. So if a guidance is saying that you can address the requirement in a way which is saying, if you have like a gap of information until the guidance comes, the same thing the guidance is saying, actually, you need to fulfill the requirement of the MDR or the IBDR. So whatever is written there, even if there is a guidance or not, you need to fulfill the requirement. The guidance is not an obligation like Tom was mentioning. The guidance is a recipe which helps you understand the requirement

and implement them accordingly. But it's not a replacement of the legal requirement. So whatever is defined in the legal requirement need to be followed and addressed. And this is what you need to consider as a manufacturer. And this is very key and important for your activities to meet the requirements. So thank you, Robert. Yes, I think it's like very important to give this message as well back to everyone to understand what is actually the expectation. So Tom, one question to you. So we hear about all of these obligations and the requirements. When is that actually expected to start collecting data for PSUR?

So when am I expected, as manufacturer to start collecting data for my PSUR? And do I have to submit that data like you just mentioned before? Can you give us like some clarity about this? What is the expectation? I will try Basil, but again, again, it all kind of comes back to what type of manufacturer you are. Are you a new device that was never previously on the market? No previous search under the MDD or AIMD? If that's the case, then the requirement. And again, Basil, keep in mind, I'm an IBD side of the house. So if I misspeak, please correct me. I will try. I will try, but I may misspeak the odd time.

So if you're a manufacturer for a new device, the requirement is a PSUR applies from the date the device has been certified under the MDR. So the data collection period is based on the date from the first device from the search. So, and the end collection point from that should be aligned to the anniversary of the search. So whatever day you get your search, that's the date that everything is going to be aligned to. And the only caveat to that is unless you have an agreement in place with your notified body. So the other type that you are is legacy devices, which I will again, legacy devices breaks out.

And again, as the notified body, we will push back on you, the manufacturer to say, you know your device better than anybody else. You give us the justification as to where you are setting your time points from. So as Article 120, I'm not going to get into the dates because they'll probably change soon enough, hopefully. And PSUR requirement is not new. So your data collection should be underway. And then again, it depends on if you plan on submitting an application for the MDR or not based on that. So there's, there really is a lot to go into. So you touched on very important points. So Article 120 or Article 110,

both of them, they have this prerequisite of fulfilling of post-market surveillance obligations. It's true. The date might be pushed with the proposal, but not the post-market obligation. They're going to remain as they are valid from date of application. So we need to be careful that we are not misreading the proposal of the European legislator. So important is with regard to legacy devices. So Marta, do we need, I'm a manufacturer of an MDD. I'm making use of the transitional additional transitional period, which is actually the grace period from, from date of application 26 of May, 2021. Am I obliged to issue a PSUR for my class three or

class two, a device, or am I able to waive that requirement? So if you're still placing the device in the market, so it's a legacy device, yes, you need to be there. PSUR. I would also like to say a few words on the legacy devices under Article 110. And 10, I'm sorry. It's still in the legacy system under the IVDR because the conditions for legacy devices and that article are specific, specific because they take into account the different classification system between the directive and the IDR and the fact that some of the post-market surveillance requirements are linked to the classification on the device.

So, under the IDDR, PSUR is required for Class C and Class D, but of course under the IDDB, the device might have been a general IDD and definitely it was classified according to different criteria. So for these devices, there is a specific, another MDCG guidance, 2032-8, that actually clarifies that for IDD legacy devices, the PSUR is not mandatory because it's linked to the classification of the device under the regulation. What manufacturers have to do in this case, they still have to have a PMS line.

They have to have a PMS line in place and they have to do a post-market surveillance report, not a PSUR. Of course, if they want to do a PSUR, they can, but it's not mandatory. Okay, very helpful guidance. Marta, thank you for that. Robert, we talked about the PSUR. There is this template at the end of the Annex 1 of the guidance, which is telling us feedback and complaints from user, distributor and importer shall be included. Now, do we have obligation to present in PSUR the result of user feedback questionnaires obtained from all of these sources? Or can we waive that? So do we need to include information like that we do in connection with activities on the market with user, with distributor, with importer?

Or what can we, what are we expected to deliver there? That would be advisable. The guidance is asking for that. And it certainly makes sense to include that. I'm trying to think of the cases where that should not be included or there would be a reason not to include it. Again, when it's not covered by the classification scheme, class one, for instance, it just becomes in post-market surveillance, not a PSUR. That would be acceptable. But ultimately, as Thomas said, the manufacturers will know their products better than the regulators. And the guidance document does allow for justification for non-inclusion of certain categories of data.

I'm not sure that really came up, but I would think that normally that would be included if that is being collected by the manufacturer. Okay. Okay. Perfect. So thank you for that. And actually, if we look to my slide where I summarize. The main intention of PSUR, it's saying that it has to include the main findings from my PMCF activities. And if we look to PMCF or PMPF activities, what is that including? It's including customer user feedback under the general methodology. So based on that, it's not wrong to include that. The second point, which is important, we need to consider that the economic operators with the MDR and the IVDR have also obligation with regard to post-market surveillance activities.

And therefore, I always recommend manufacturers to consider updating their contract with their economic operators to consider getting those data. Because all of these data need to be shared to ensure actually that you are getting the right message from the market and you are able to continuously learn from the market experience with the device. That's very well said, Basile. And yes, I've worked with IVD manufacturers and certainly in the IVD space, there is a lot of economic interdependence, you'd call that, between different manufacturers. And sometimes the actual manufacturer is at some distance from the end user.

And there's a strong encouragement in the end from the European regulations to try to bring those entities together. So that applies, I think, in a general way here. Yes. Yeah, perfect. So, Tom, listening to all of these, and we are getting a huge amount of questions. So this is why I kind of keep calling to make sure that everyone is getting an answer from all of us. So just a question, a quick question for you. I started working on my PSUR, I'm a manufacturer, started working on my PSUR and prepared it. Now we've got the guidance. Am I expected now to rework, to reformat it in accordance with the guidance?

Or can I keep my initial guidance or initial template, which I have created as an organization, and disregard the guidance? What do you think? It's a very good question. And it's one of those questions where you really need to consider. Consider the guidance and then consider the data that you have prepared. And then you're going to naturally know, yeah, I think I'm nearly there. And if the answer to the question is I'm not really nearly there and the guidance is now telling me that I need to consider a lot more. As a notified body, we are going to have to take into consideration the guidance.

So, again, I would say you should probably consider a small, a quick gap assessment. But again, this is. It's not going to come down to where you where you are in the process. Have you just started or are you you've been working on it for the last you've had your Reg Affairs team working on it for the last two or three weeks and they're coming to an end of it. And then the guidance document is out. The guidance documents been out now since December. I would say that the answer is somewhere between both of them. But you need to have a consideration for it and a justification for why you're going to say that your data is acceptable.

Again, it all comes back to if you're not going to. Like I think. I think we've all said it now. Robert has definitely said it. You need to provide strong justification and rationales for why you're not going to do something or else you need to show compliance to the requirement. That's kind of where everything comes back to. Thank you for that. So, in summary, I have to follow it. You should consider it. You should consider it. It's a notified body answer. It depends. Well, it depends. It depends on the data. You could you could say that I look at the guidance document and go, that's great. My dad really meets the requirements of this guidance document.

I don't need to do anything else. Or you could consider it and go, oh, it looks like it appears I've got a couple of gaps here. I haven't considered Kappa. I haven't considered complaints. I really should go back and do it because you will have to go back and do it. Perfect. Thank you for that. Thank you for the summary, which means it's highly recommendable to follow MDCG guidance documents to avoid actually discussion. If you if you have a good justification, you can start the discussion. But it's not recommendable to do. So. So, Marta, considering what we are hearing here, we've got a question about schedule.

If I have a class to a legacy device, when am I expected to deliver the PSUR? So you should start by following the legislation. The schedule is recorded in the legislation, depending on the classification of the device. The starting point would be the moment to get certified. With under the regulation. Now, what the regulation actually says is at least. For example, once per year, you can decide and you can agree with the body to do a shorter timeframe if you wish to do so.

But in terms of frequency of submission to be at least the frequency indicated. Then. In. Article 86 or 81, depending on which regulation is applicable to your device. Thank you, Marta. So referring to the timeline, just to answer that to a devices at least every two years to be devices at least every year, class three devices at least every year. And you need to consider as well which devices requires an upload to Udemyt implantable and class three devices need to be uploaded to Udemyt whenever Udemyt is available. And they're not. Not. But you will need to review them over the Udemyt system as well.

So Robert, a question for you. It's a tricky one, but I'm pretty sure you can handle it. How can one define a threshold for trends reporting for legacy device that has not been sold so far? A legacy device that has not been sold so far. That's an interesting category. So this would be okay. So it had been put together. Under MDD or MDD, but had not been placed on the market, actually not been sold. So again, the question is for that kind of device. What was it again? I didn't catch what you'd said.

So the question was, how can one define a threshold for trends reporting for a legacy device that has not been sold so far? Well, my experience has been that it's incumbent upon the manufacturer to define the triggers for trend reporting. And normally, if you have something that has sold thousands of units or higher, then you can do a sort of a proper statistical analysis. And you can say if you are outside of a certain number of standard deviations and so forth. If you haven't had it on the market, it's a good question. I don't think that there is really a specific, you can't do a statistical analysis of N of zero.

I think you're going to have to start, and I look to you and others on the panel here to kind of look at this as well. You have to start looking at what the sales data are, what the actual usage data are. And then start forming kind of a range of what would be considered out of the ordinary. But ultimately, I think it's something like this is essentially some form of a new product. And if it had been formally available under the directive previously, I think that it would be advisable to be conservative on the part of the manufacturer. Meaning that any problems or issues that have to be investigated should be included.

Because again, even kind of one or two things showing a problem could be an issue when the device has not really been in use in a lengthy way. But I look to you and others to also address that further as well. Thank you, Rob. So I know this is a very tricky question, but my recommendation to all manufacturers, if you have such a device, like you have a new innovative device as well, you have a new device which is entering the market for the first time. What you need to do is like you need to define based on your best knowledge and your best knowledge would be actually searching the literature for a similar device.

A device which can contribute to help you actually preparing your threshold, which can be adopted automatically. So you can build up your threshold over the time when you get your experience. So if you don't have experience with the device yet, so you can use experience from similar devices, build up your threshold, define it. And then based on that, you have a strategy forward. And then when you get to the market, you can actually review again and adopt and make sure that you have a continuous process of implementing the requirement. Makes sense to me. So looking to all of this, Tom. I would recommend for every guidance which comes out, someone is telling us the guidance is poorly written.

Is there any awareness of reviewing the guidance for clarity? What would be your view? Do you have any feedback on that? I see you shaking head. I shake head a lot of time because you can't write in the right way. You will never get it right. So tell me. Exactly. It's, this is with guidance documents. Nobody, the audience is never going to be 100% happy. Personally, having read this document, I don't think it's the worst. I quite like the flow diagrams in it. I think they're useful. But again, the guidance is most useful to people who, to manufacturers who understand their product well. It is technical and it is complex in places.

And you really need to spend time finding where the guidance is appropriate to your device. Because not all of it is going to be applicable to every manufacturer. So it's important to know what you can ignore. And that's true for the regulation. It's true for any standard as well. If it's not applicable to your device, put a line through it. Do I think this guidance document will be updated or reviewed for clarity anytime soon? Based on experience for previous guidance documents, I would just say, no, it's not going to be. We might get a REV 1.1 maybe in 12 months if there is a lot of pushback against it.

But I don't believe that will be the case. That's just my own personal take. I do think from what myself and Martin would have heard at a European level, there will be a specific IVDR guidance document. But I don't expect that to come in the next three or six months. I hope I'm wrong on that. Maybe towards the end of the year. Thank you. Thank you, Tom. So I totally agree. And I think, you know, this document is not like a document which you create over the weekend. There is a lot of contribution towards getting such a document. And it's not just like one single person creating. There are like multiple member states involved.

We have here notified bodies also involved to some extent by giving actually then input during the holistic process. I think the process started three years ago. So it started in 2018. And at that time, this was the initiation. And we had already a guidance which was prepared in the final version. And then it was dropped. And then new work started again. So I think we should make use of the best of it and make it actually reasonably implemented, like you said, by looking on how to implement the requirement in the right way. I might, Basil, just jump right back in there. I think I saw a comment flashing by recently to say that there was a lot of changes from the previous draft version, the final draft of this document before it went up.

And that person is correct. There's a lot of changes. Maybe one thing we might see is maybe the annex for the notified body. Maybe we need to come back in again at some point. I would personally welcome that as well. As I think of it, maybe that's the only thing that might come back in that might prompt another review of the guidance. That would be it, I think. Okay, perfect. Thank you. So for all of you, I will keep it open to see who can react. We have IMDRF coding. Is it mandatory for PSUR to include IMDRF coding and to follow them? Maybe I can start with answering this. So, yes, there is a reference to IMDRF coding specifically for serious incidents and the expectations that they are used.

IMDRF coding has been around now for a few years for reporting serious adverse events. So serious incidents, I should say. That's the correct analogy. So serious incidents. So they should already be implemented to code this serious incident and to report this incident using the manufacturer incident report. So in the PSUR, you would need to summarize what is, which serious incident is. And then you would have to do a lot of work. Which serious incident you got for which code. Also, they are very helpful from a notified body standpoint to really monitor, I would say, the frequency of a certain type of serious incident.

So, yes, IMDRF adverse event coding should be used. Thank you, Marta. So you answered the questions. Two questions, actually, in one sentence. Okay. So, thank you for that. There is a question from the attendees regarding PMCF report, PMS report, PSUR. So the PSUR, is the PSUR actually replacing a PMS report or are manufacturers expected to have PMS report and PSUR report? Tom, do you want to take it? For any particular type of device or just any type of device? In general. General question. General class one PMS plan, PMS report, everything above a class one PMS plan, PSUR is my interpretation of it.

Which is correct. So based on that, actually, we just have a PSUR for devices which require PSUR. No double reporting. You don't need to have both reports. I'm very much what's the requirement. So, yes. Thank you. Thank you. So, yes. And if the person asking the question, if someone is looking for a PMS report and they're not a class one, I would say what's the requirement to have them? Perfect. Thank you. There is a requirement saying is PSUR required. There is a question saying is the PSUR required while renewing the currently valid MDD certification of the device as there is an extension in the current transition period?

Robert, do you want to take that? Oh, yes. This is a. Is PSUR required while renewing the currently valid MDD certification of a device as there is an extension in the current transition period? What do you think? Yeah. Right.

So, there have been delays for both medical devices and IVDs in terms of other aspects of what needs to be done and the dates for that. Yeah, there is one command and leave it to you all that just you discuss and let me know who you want to ask, who want to answer. I'm happy to support as moderator and add my input needs some insights regarding the evaluate. How many patients have been exposed to the device? and the characteristic of the exposed patient group, it will be challenging to identify the patient count apart from regular states, specifically characteristic of the patient population. Anyone who wants to start commenting?

I can start with an IDD perspective. So, of course, it's difficult to know how many patients exactly have been used and what are their characteristics. But depending on the type of device and also taking into account not only how much tests you actually sold, but elements such as the need to run controls, for example, together with the patient sample, you can derive an estimate of how many patients could have been tested. So taking all these factors into account, of course, what is important is that you clearly explain in the IPSUR

and justify the approach you take to provide this information. Thank you. If it's OK, I might just have a little follow on. I saw one of the comments earlier asking if the templates in the MDR guidance would be applicable for IBD or PSUR. I think Marta's answer would hopefully answer that question again. I think the number of sales, for example, doesn't really translate from the medical device side to the IBD or PSUR side because you might be selling a 96 well ELISA assay with calibrators and controls on it and you might have to run your samples in duplicate or triplicate. So again, it will be up to you to explain in your PSUR the analysis you have done

and your data to show why the numbers on the tables are relevant. So it's not really a lot of work. Thank you. Thank you. Thank you very much. Thank you for like. Yeah, I think I think what is important here when we talk about sales and estimated usage is actually to use your marketing team, your market experience and to see how is the typical distribution that I had in the past? What is actually the expectation for which market? And I think you're very important input will come actually from your sales team with regards to that and medical professionals who are supporting your market entrance.

They can give you like an understanding about how is the market size, where the devices are used. You can use also your previous experience with these devices to establish those number. And like I said, this is a continuous process of improvement. So you kind of put numbers which need to be adopted over the time to make sure that you are meeting the better requirement over the time. Post-market surveillance lives actually from reality from real evidence from your experience and based on that you establish actually future for your post-market reporting which enable you to say what can be done and how acceptable are the results that you are providing.

As manufactured. So if we move forward and we look further to I will take one more question before actually getting to the end because we are like having hundreds of questions. I know everyone is excited and we can keep running with a lot of questions, but let me take this one. What is the best practice to process PSU are PMCF report CR and risk management update short. For example, the DCP be the same in all of those documents. But which one to approve set effective first and then copy and reference and the others. They all need risk-benefit conclusion Robert. You want to take that? Yeah, this is a good one.

This comes up. I think in all cases in so many different contexts and I don't know if I have a very simple straightforward answer for that. But I think you need to look at the current documentation you have and the cross references you have for them and it may not be a very satisfying answer. But I think the answer is yes in a certain sense. You have to kind of look at all the documentation and the links between those and update those in a sensible way. Sometimes it is essentially simultaneous. In some case there is PMCF or for IVDs PMPF that's been performed and that documentation has been signed off and approved and then that feeds into for instance, a PSU are so

I think you're going to be different cases. There are some cases where one clearly feeds into the other. But then some of the other ones with the risk-benefit analysis, there is actually I think a two-way street going on there. And I don't know if others have you know, other other ways of looking at from their experience as well. So I think it really depends on the situation. I would agree with everything that Robert says and it also it also depends where you are. Are you at the start of the process because it will be different from the start of the process as to when you're continually updated updating and working through it.

So the process you put in at the place. Sorry, the process you put in place at the start will naturally have to change to accommodate the continually updating of your documentation. Thank you, Tom. Thank you, Paul's for the feedback on this totally agree. I think you need to do the process mapping. You need to understand which process has which input expectation which process has which output expectations and based on that you can need to connect the dots and like it was said I mentioned all of them expect benefit risk. Conclusion, but that could be actually a contribution of all of them same time or making

sure that that benefit risk conclusion is updated in the second document. So it doesn't need to be hundred percent the same because post-market report is actually confirmation of the data and your initial conclusion. Whereas the CR is actually the input for post-market clinical follow-up activity post-market surveillance plan. So you need to consider all of these when preparing your process and you establish them your future future process considering the requirements. Which are applicable for your kind of device. I'm looking to the list of question. My eyes are rolling down and it's like wow, it's like I see that we have a guidance document,

which is actually prepared to answer the questions of a lot of manufacturers. But Sean looking to that. I think we can do like 10 of these events and we still have a lot of questions to be addressed. I'm very happy and thankful for Martha Tom and Robert for contributing today to this event helping us actually understanding the requirements and understanding the requirements. Understanding what is the expectations so summary which we can take it's a guidance document. It's not a hard stop to say you need to apply it immediately legislature became more reasonable in Europe. So they said an MDCG document is actually a guidance which you need to consider and

implement Tom told us about how important it is to follow the guidance because notified bodies are expected to do. So Martha told us about actually the need also for PS you are not just for new devices, but also for Legacy devices. And that we need to consider also the update schedule, which is essential, which is defined in both MDR and IVDR. And what is very important what actually was the last question Robert input with regard to also the processes. So you need to establish and implement processes within your organization to meet the requirements. It's not about just doing ad hoc something based on an immediate reaction.

You need to establish the process. You need to train your people. You need to ensure how many is it approach and the implementation of the requirement. Don't forget. And I saw. This question multiple time, even so I said that during my presentation, it's a stand alone document. It should be readable itself. You can't cross reference other document because they are not accessible for the authority for the notified body at the time of the submission. If you cross reference a lot of document that you make out of your PS, you are complex document. It will be not readable and then you will get a lot of document request and the process

will explode. So thank you for listening to us today. Thank you, Martha. Thank you, Tom. Thank you, Robert and the big thanks to Sean who organized this event. I will give it to you back and you can close this event on please. Thank you everybody for attending. I will endeavor to transcribe this and to answer as many of the questions as I can. And there's there were a lot of questions in the Q&A. Perhaps we didn't get to some. I will try to triage those and distribute them to the speakers and hopefully we'll be able to get back to you with some sort of satisfactory answered, but I can't promise

that. So I will try to do that. And thanks everyone for attending. This was hugely popular event. There were lots of questions and we look forward to doing more of these events in the future. If you have topics, please feel free to send them to me directly at Sean at Huma dot AI. Thanks. Thank you everybody. Bye. Bye. See you guys. Thank you very much. I'm thank you guys. Thank you everyone. Thanks everyone. Bye.