 Hello everybody, and thank you for the opportunity to share some insight about the analytical validation of IDEs, I'll just jump into the topic, I'm glad to be here. So I actually am a reviewer at the Division of Microbiology Devices, so I'll give a perspective on IDEs which are submitted for infectious diseases. So typically when we get IDEs, which is very rare, I would like to say that most the majority of the studies you won't really need an IDE, but when we get them in the infectious disease area this will be for markers, for example viral or microbial markers which could could help in as a prognostic marker, for example for cancers or for or diagnostic markers. So it's mostly for those studies that utilize or detect the virus DNA as a marker for whether it's saying that this individual has an increased risk of a certain cancer, for example. So in my talk today I'll just, so these are not genetic testing that I'm talking about, it's molecular tests, and I'll quickly walk you through the analytical studies. In the beginning I'll just touch on the principles of an IDE submission and I'll talk about the analytical study requirements and wrap up. So as you probably heard in also the previous talks, for a successful IDE submission you would like to cover these pages, clear and precise intended use, a complete device description, scientific evidence supporting the intended use, analytical performance and labeling. Essentially what you need to do is show us, give us enough evidence to help us understand what your device is and how it does what it's intended to do. And this slide I won't go into the details of it, but the intended use should cover all these aspects, so it should help us be able to understand the indications, for example if it's risk stratification or aid in diagnosis, clinical context, and also to understand what the patient population is, the different sample type that is used for the assay and the technology. So sufficient information about all these four aspects. And this will help us in understanding what kind of analytical performance are needed. Last description, typically what we would like to see is a description of the principle of the test from the beginning, from the sample, all the way to the result. And also a complete description of the agents as parts or components of the assay itself and how the target was selected. Again this is with focus on molecular test, how you pick that specific region or that specific gene from the virus that you are testing for. Any instrumentation involved and the quality control and procedural limitations of your assay. We would also like to see how the results of the assay are interpreted. So a list of the possible result categories and the recommended interpretation, for example for quantitative tests, if you could define the different levels of the quantitation and their clinical significance for qualitative tests to describe how a positive versus negative result will be used for patient management and also the equivocal result if you have that as part of your assay. And to define any other clinical information required for the test interpretation and patient management. For example, if your test is not a standalone, like in addition to this test result you need to use this other marker or this additional test. All this is building a good understanding and these are the concepts that could be applied or you could apply them to any technology if it increases complexity, changes in technology. The core is to help us understand what the test is, what does it do, how does the result, how is the test result used for patient management. So after that the analytical studies, the analytical performance studies are quite typical. It's what you do in the lab. So if you take how we validate our assay in the lab to see that a positive result is positive and it's repeatedly positive, essentially this is the start point. And then you could think about depending on what the assay is, what the analyte is that you're looking for. How frequent is it available in that body compartment or sample type that you're looking at? You could think about a very or a diverse level of requirements that you could think about. So precision, reproducibility, analytical sensitivity, limit of blank, limit of detection as applicable, linearity, traceability. And we would work with the information, also sample stability, matrix effects, reagents, stability, cross reactivity and interference. And what I would like to, I think I would like you to take home from here is think about what you do in the lab to evaluate. Think about all these topics or all these points that I mentioned here as the typical performance studies that you would do in the lab for you to be comfortable that these performance, targeted performance are met. We take what you bring to us and we can tell you if this was enough. So we're not going in an ID submission. We don't say you have to test exactly this number of samples. To show us that a nasal swab was stable when it was stored from so and so and you could still detect this. Or we won't tell you that for a cross reactivity study you have to test all these analyzes. But we want you to think about all the common agents. For example, if you're testing for EBV virus, think about all other herpes viruses that could be available. If you're thinking about BK virus and JC virus, if these are two different viruses that typically would cross react, then a good, a good study that demonstrates that there is no cross reactivity or if there is cross reactivity interference with common medications that could be found in that sample type. If it's a swab sample, if it's a respiratory sample versus if it's a skin sample, a muco-cutaneous or cutaneous sample. And the same applies for the precision, the analytical sensitivity, the linearity. These need to be addressed. And we could accept or look at different levels of study that are performed on a case-by-case basis. And we struggle, like you do, with determining what is the minimum requirement. However, we all utilize or go back to the same standards. So for example, traceability and commutability for quantitative methods when there is no reference standard. And I put here, and I'm not going to go into detail, but these are all standards that we recognize for meteorological traceability, ISO standards. For linearity, we look at CLSI, EP6, commutability. And this is the definition here for commutability. But due to the time constraint, I won't go into details, but basically we want to see that you address all these elements of the device performance. And if there is an available international standard for the analyte that you're looking at, we strongly recommend that you do that. We also accept data that's collected from different studies. For example, in some cases, the labs have performed a harmonization study, where the results of the analyte have been shown to be equivalent and be transferable to a reference material. You can get sometimes or pull out data to support different study from a study that was called differently in your hands, in your lab. So there's a big nomenclature gap. But if you send us what you did, we could break it down as well and discuss with us in pre-submission that I have a performance study that did this and this and this and this. And I compared all these aspects, and I was able to find this material. It could also be sufficient for us to fill gaps in precision, in reproducibility. And for standard materials, also likewise, maybe different nomenclature, but we struggle with calibration, hygrarchy, sample types, and well-characterized panels. EBV, for example, for an IDE, there's no standard material that is available for nasal swab samples. But there's WHO standard, which is available, a quantitative standard for blood samples. So sample type is different, and adjusting the standard material to a different sample type is also a challenge. So the common goal, our goal is the same. If there is a device that you believe could help the public or help a specific target patient population to achieve something, then we would like to do the same thing. We want to get with you to the same spot. So a pre-submission, it will be a good place to start because we understand that there's a big, huge gap between labs, for example, or assays which are developed simply and what is required for a pre-market approval of clearances. So, however, given that common goal, we work together to understand how the assays perform and sharing protocols of assays and data that has already been collected, submissions and so on, papers, all this could happen in the pre-submission phase for the IDE, and we strongly encourage that. So I think we have touched on or covered the principles of an IDE submission for vital vitro diagnostic tests, for example, and talked about the essence of the analytical study requirements. And I've provided some additional slides which will guide some thinking and might be useful for the participants to understand more detailed aspects of what's a device and an IDE submission in general. Thank you very much.