 Great. Thank you. So, first of all, I want to thank, reiterate a big thank you to Rebecca Hong, who really did a lot of work that made this day possible, as well as Christina and Laura Rodriguez and Dr. Green. As he mentioned, this is part of a larger effort, which has been really helpful for us, and we hope for NHGRI as well, and we look forward to continued activities like this and in other realms as we work together to move genomic medicine forward. So, what I'm going to do right now is to talk about, just give a general overview of IDEs, why are we here, why are we talking about genomics, and sort of set the scene for the rest of the day. So, just to give a little, you know, sort of history of this, I think, you know, if you were to look back 20 years ago or so, the research and, you know, research like genomics, research that was funded by NIH, largely did not intersect with investigational regulations for in vitro diagnostics. Certainly, drugs, traditional devices like, you know, heart valves or new implantable devices have always been regulated, but just because of the nature of the technology and how it was used and the focus on basic research, it's not something anybody really had to think about in the sort of academic, basic science research world. But today we're seeing much more of an intersection, and this is because of the promise of the technologies that all this basic research has led to, and as a result, the emphasis, the increasing emphasis on translation and on moving these technologies into the clinic so that they benefit patients. This is something that we all support. We all benefit from, and it is part of FDA's mission to get new, innovative technologies to patients. So we want to support NIH, and HGRI, and other institutes at NIH in this effort. However, one of the challenges has been the increasing, this increasing overlap with clinical, with regulations that govern clinical use, and for tests like genomic tests and other types of tests, as they move into the clinic, they are falling under the scope of the investigational device exemption regulation, which regulates investigational use of in vitro diagnostics and other devices. And we'll talk a little more what we mean by investigation because this is one of these terms that we have a very precise meaning, but you could think of it more or less as human subjects research. The change in scope has not really been an issue because, and I think naturally so, people have not been aware that this regulation even existed or that it applied to the sort of research that people who have been not just funded by NIH, but in other spheres have been doing. And one of the examples and one of the reasons we're here is from an incident that occurred, you know, several years ago now where an investigational test at an academic medical center was used without complying with the IDE regulations, without all the oversight that would have been required. And it was used in a, it would turn out to be a test that had, that did not work, that was based on false and maybe even falsified results. And it was used in the setting of oncology and harm patients. Patients sued the institution. It also led to an IOM report, which I list here, and they had a number of recommendations, and this is back in 2011 or 2012, as we were beginning to see this explosion of omics moving into the clinic. Couple of those recommendations were that FDA needed to step up its efforts to communicate what these requirements were and how they applied to omics. And also to engage in a dialogue with the community to develop, not just to educate, but also to help develop better ways to provide oversight for this technology. So this conversation is very much in that vein. This is something we've been working on for several years. We believe that education and dialogue is the best way to make sure that everybody not just meets the regulatory requirements, but that we apply those requirements in a way that makes sense and that benefits everybody, including the researchers and the scientists who are developing these technologies. So we are here to tell you about the regulations, what our thought processes are, how those apply to genomics. But at the same time, hearing from you is very important because like everybody else, we rely on the latest science and we apply the knowledge that is available. And as knowledge changes, we need to change. We need to update our thinking as well. We also feel that speaking with NIH is incredibly important because we recognize that academic researchers, NIH-funded researchers often face special challenges. Many most have not had prior interaction with the FDA, or even if they have, they haven't had prior experience with IDs. Most of the people, most of the academics who have interacted with FDA have done so in terms of either traditional devices or more commonly with drug regulations, which are in fact rather different. This means that people don't know what to do, but it also leads to communication gaps where it becomes difficult for us to even communicate what the requirements are or for you to understand them. And so one of the things we want to do as an outcome from this workshop and from future conversations is to develop better ways of explaining this and outlining what the pathway is. Many people who are in academic settings don't really have adequate regulatory support and I don't mean that institutions are doing anything wrong, but this lack of experience extends to the institution and we recognize that many NIH-funded researchers are not in industry where you have a regulatory staff that will take care of all of this. And there's also the time-limited nature of NIH-funded research. When you get a grant, when you have a grant or when you award a grant, this is for four years or five years, you're under the gun. I think most of us all know what that's like, what that time pressure is like. So having an additional regulatory step to undergo can have a significant impact and we want to minimize that impact. It's important to point out that when we say, when we talk about applying to ID regulation, we're not saying the research shouldn't go forward. We're not saying that people are doing anything wrong. This is a part of our legal system of oversight for patient protection in the United States. So the purpose of this workshop is from, at least from our standpoint, is first to help you understand the ID regulation because understanding it will allow people to be prepared ahead of time. The best time to know what you have to do is as you're planning your initial study. Planning ahead will make the entire process easier. You'll have every, you will be much closer to having everything you need at the beginning of the process and we don't want to disrupt research or research projects. So we want to have people understand this at the beginning. And then, you know, in having this conversation to identify barriers to meeting ID requirements is important to us because we want to help people overcome them. And so understanding those barriers will help us, help us do our job in helping you, you know, follow the ID regulation. So just a few points about the ID regulation. This is a quote from the Code of Federal, this is text from the Code of Federal Regulations, which is defines what the ID regulation is. And the purpose is to allow investigational devices, including IVDs, to be used in research by exempting those devices from all the requirements that a normally marketed device would have. So, you know, if you're going to sell something, you have to get an FDA approval and meet all these requirements. And the point is, at the research stage, that doesn't make sense. But we also want to make sure that those investigations are conducted in a way that protects public health and safety. And that is ethical, meets ethical standards. And so we have that goal as we look at IDEs. Now, we can talk about IDEs as an exemption, but we also refer to IDEs as a regulatory submission that permits clinical investigation of devices and IVDs. And as I said, this allows, you know, you to use a device in an investigation without complying with other requirements that you would for marketing. It's focused on risk and they are delegated responsibilities, which means that a lot of the responsibilities for making sure there's compliance with ID do not lie actually initially with FDA, but they lie with the investigator or the sponsor and their IRBs. And you'll see a little more during the day how that works out. But getting an IDE approval when you do have to make an ID submission, you know, when we're looking at an investigation, we are trying to ensure that risks are out, you know, outweighed by anticipated benefits to subjects, that the informed consent is adequate. Again, this is the ethical oversight. And that the investigational device plausibly is effective, you know, so that you're not using something crazy on people and somehow posing risk to unnecessary risk to them. And so that third point really will get into one of our topics today, which is analytical validation, that when we are reviewing an investigational device, including an IVD, we need data on how that device performs. Now, how much we need will depend, as you will see, but that's sort of one of our major questions in one of the ways in which we primarily look at safety. Now, a few points about FDA review, because I think often we're viewed as a monolith, a black box. And I think it's sort of scary to people, but we're actually very friendly. We're fun to talk to, as you will see today. But there are aspects of FDA review that I think people would appreciate, and I think would be a value add. So first of all, it's highly interactive. So this is, you know, during the course of a review of any submission, there are many opportunities for informal or formal conversations between an FDA and a sponsor, i.e., the person who's submitting whatever the application is. You know, if information is missing, you may get an email saying, I need to know this. Or if there are questions, you can contact the reviewer. It's not a black box. You know, there are many opportunities for communication, which makes the process be more effective, and helps get people to approval. We also have a more formal pre-submission process that you'll hear about, which allows conversations before submissions, which allows you to answer some basic regulatory conversations. And this is a huge benefit to people, because you can determine exactly what you need to send in, if it's worth sending something in, or if you even need to send something in. Also, the important thing to know is we don't apply a single standard to all of each of our diagnostics. The review really happens, and the details of that review happen on a case-by-case basis. So what is required will depend on a number of factors. What is the actual test? What is its intended use? How is it going to be used in the investigation? What's the design of the study and other factors? So we aren't going to apply or, you know, we don't apply requirements to IVDs, or we try not to when it's not required, when it wouldn't make sense for that IVD or that technology. And so we really often times, the IDE review process worth tailoring the review to the way the different risks can be mitigated in an investigation. The last thing I want to point out is that this is really a different focus than peer review, and it's different. First of all, we're not looking primarily at the science of your study. We're not making a comment on whether the study, what the value is, if it's worth doing, how much it's going to contribute to general scientific knowledge. We're primarily evaluating safety and ethics. And so even to the degree that we overlap, we're sort of looking at it through a different lens. And part of that is analytical validation, and one of the things we want to address today and in the future is what that means in a really detailed way so that people can understand. Because our review of analytical validation is very detailed, or can be very detailed. It depends again on the context. And it can even include evaluation of lying data. So you would send in all the numbers that have been accumulated. It's more true with pre-market submissions for marketing approval, but nevertheless it is something we do look at. Now, we're spending a whole day talking about the IDE, but I do want to point out the good news, which is that most studies of the feature of diagnostics will not require an IDE and will actually be exempt from the regulation. This is, you know, given, so an example would be a very common study, use of archived, de-identified specimens is almost always exempt from the IDE regulations, which means, you know, if you don't even have to worry about the entire process, then if you are in a situation, and this is just one example of how something can be exempt from the IDE regulation, some of the studies we see are really exempt. Some studies aren't, and then we have to make a determination of whether the risk posed to patients is significant enough to require an IDE submission. And you'll hear about that process. But even in the realm of studies that aren't exempt, most studies do not reach that bar of being significant risk. We actually receive very few IDEs, and I'll also say of those, almost all of them are approved. I would say, though, that this is something that could change as more technologies move into the clinic and more people use them to take, you know, even in an investigation to take potential actions about their health. And that's something we can discuss later. Now finally, I just want to say a little bit about our office, because this is, you know, if you were to submit an IDE or to deal with us in some way, this is who you'd be dealing with. For in vitro diagnostics, we have, so we're the office of vitro diagnostics and radiological health. So that second part, radiological health, we actually have two divisions within this office. Radiological health and mammography, you can ignore those for today. We don't, I don't even know who's in that of those divisions. But the four that deal with in vitro diagnostics are DIHD, so this is immunology and hematological devices, molecular genetics and pathology or GMGP, microbiology devices, DMD, and division of chemistry and toxicology devices, DCTD. So today when we're talking about the IDEs, we're going to be talking about a range of types of studies. So not just genomics and the sort of, you know, whole genome sequencing and returning results sense, but also in the context of, you know, specific types of diagnoses or specific trials of investigational drugs, where we see probably most the bulk of our IDEs at this point. The other thing I want to point out is that the people who work in this office come from a range of backgrounds. They, almost all of them have advanced degrees, PhDs or MDs. Most of our medical officers still do some practice, so they're not, you know, they still are, you know, involved in the medical community. They come from clinical labs that some of them have run clinical labs. Some of them come from a more pure research. So we have a range of experience and expertise. We have software experts. There are statistical experts. We can, we, when we review something, we assemble a review team as necessary to address all the things and we actually can access anybody in the FDA. So even for ethical review, we can, we have people we can call on. The other point I want to make is that the people who do review, and you'll hear from some of them, from them today, are experts at reviewing in vitro diagnostics. So somebody who focuses on a specific type of test or technology has seen every variation. They know every way in which that test can go wrong as well as anybody. And they're used to reviewing tests, I mean, really, if you think about a test going into the clinic, that test has to be reproducible. It has to be able to generate correct, accurate and reproducible. It has to be able to consistently generate correct results because with a patient, you have one shot in most cases. So as we talk, as the field talks about reproducibility, designing better research for clinical work particularly, I would hope that, you know, the field can leverage the expertise that sits in OIR. I think because of the lack of interaction in the past, because there hasn't been this intersection, people may not realize that, I think FDA is not just, is sitting on a resource and that's one of the discussions I also hope we can have in the future. I know the reviewers are thrilled that I'm committing them permission. Even more work. So just to end with sort of an overview of a day, the day, this is sort of a very general flowchart of the thought process. What we want to communicate to you today, there's too much, there are too many variations and details to even cover in the course of one day. But if you walk away with anything, it's the thought process you should be applying. And you want to know when and how to come to FDA for help. So you're going to start with some sort of clinical protocol that has an investigational device or a clinical protocol and you're going to just ask, is there a device? And if so, is that device investigational? I mean, would it even be subject to the IDE regulation? And if it is investigational, if it's exempt or not? And I can see on my yes and no backwards here, because if you're not exempt, then you move on to determining what the risk is of that investigational device, including IVD in the trial. If it does not rise to a level of significant risk, you have a limited set of requirements, what we call the abbreviated requirements that you comply with and you're considered to have an investigational device exemption and you can proceed with your investigation. And this all assumes, of course, IRB approval and all the other regulations, you know, meeting all the other requirements. If you do rise to a level of significant risk, you also have to submit an IDE and get that approved by FDA, which happens is by law, a decision has to be made within 30 days. So it can be a very, you know, the review itself is fairly rapid. Once that's approved, you can proceed with the investigation. If for some reason it were to be disapproved, you just address the issues that will be laid out in any sort of disapproval, submit an IDE, the second IDE, and proceed. There's no limit to the number of times you can submit and there's no equivalent to a paid line. We aim to approve IDs. That is our goal and we approve almost all of them. So with that, I'll end and we can move on, I guess, to addressing some of the details. Thank you. Thank you, David. Our first session is aimed to address the question of what an investigational device is in the context of genomics research. And as you can see on your agenda, the questions we would like to get is for our community who are relatively new to this, what is the definition of a device in general? What types of technologies used in genomics research could qualify as a device? A lot of these questions on the agenda today were developed from experienced researchers had, so we're hoping to elucidate those a little further. Our first presenter is Dr. Stephen Kingsmore, who is President and CEO of the Rady Pediatric Genomic and Systems Medicine Institute at Rady's Children Hospital in San Diego. He's part of the Newborn Sequencing and Genomic Medicine and Public Health or Insight Research Consortium. Thank you for joining us today, Stephen.