 Thank you, if the speakers want to come up and sit at the front to answer questions. And I recognize that we're a little bit over on time, but we do want to leave plenty of time for questions, so we will adjust on the lunch break accordingly from here. I had, so to start off the conversation, I was wondering if we were discussing earlier the analytical comparators. So do you have a sense of are there even any analytical comparators available in the sequencing space at this point in time? Is that one of the underlying issues, or what would you recognize as that? So, Johnson mentioned Sanger sequencing, so it's still widely used in the sequencing field, in the sequencing community. And of course we recognize the limitations of the Sanger sequencing, such as the sensitivity is lower than the next-gen sequencing, but that's how we get to the analytically validated comparator method for some of the variant types or for the frequencies of the some variants that you can use like a droplet digital PCR. We have been having conversations with investigators or sponsors. Dr. Berg to walk through maybe the sickle cell disease example that you had attempted us with, which might help us cut through a fairly technical series of conversations that have been very helpful, but I think I'd be interested in hearing that. So, and presumably the slides are going to be available, people can look at them. The point of those last couple of slides were really just to say that, you know, if you look at the breadth of clinical genetics and how simple things can be or how complicated things can be, at the one end you have something like sickle cell disease where it's a single variant that causes a single disease, it's a clinically recognizable condition, there's gold standard, pathodemonic, hematologic findings, diagnose that condition so you can know who has it and who doesn't, and then the, you know, the finding of that one variant or not, you can very clearly identify if your assay does the trick, right? But no one would use next-gen sequencing to diagnose sickle cell disease, right? But then if you take it to something like cystic fibrosis where there could be hundreds of known pathogenic variants, then you could validate each of those variants, but then you're also missing some of the rare variants that could cause that disease, and so, and then you move to something like a multiplex, you know, ovarian cancer, hereditary cancer panel, you've got multiple genes, you've got lots of variants in those genes, and then taking it to the sort of most ridiculous level, intellectual disability where there's upwards of 800 to 1,000 different genes that could be implicated, how could you possibly validate clinically the sensitivity, specificity, false positives, false negatives of a condition like that? So that's just, I was trying to get to that, you know, it becomes a very daunting task if you get to the point of trying to validate those things. If it's just strictly the, can you pick up a missense mutation? Can you pick up an insertion? Those types of technical validations, I think, could benefit from just reference materials, and it wouldn't necessarily have to be specific to any one disease. Did you want to address any of your other cases, Jonathan? No, I just, I walked through the four that I gave, and people can look at the slides if they're, okay. Hi, I'm Tara Burke, the Association for Molecular Pathology. This may have been mentioned, and I apologize if it already has been mentioned. I was wondering about the total time of the ID, the submission process, and I was wondering if I could hear kind of an average from the FDA and also Dr. Burke's perspective on the timeline as well. So from FDA's side, the review timeline for ID is 30 days. And from the researcher's perspective, I think if you were a biotech company and you had an entire division of regulatory people whose job it was to produce documents, yeah, you could probably whip it out in a week. You could have all the documents. You've already got some stock materials. For researchers who are being asked to do this for the very first time, it was a really steep learning curve, and it took us a long time to even figure out who at our institution had any knowledge whatsoever of what the FDA would want from us. And frankly, those people knew about drug studies, had no knowledge of what a sequencing study would require. So we were pretty much alone in trying to figure that out. And in the consortium, we talked a lot on the phone about what we were all doing, but it literally did take months. And part of that's because a principal investigator that's on a study for 20% time has 20% of their time to spend. And they're spending all their time doing the IDE submission or whoever else they have to get. So just within the confines of how academic research is done, preparing an IDE can take months. And that's really the reality of it. Yeah, and I guess a little bit of a follow-up question to that is, and I see that perspective as the researcher kind of in your lab and you're focusing on that, and then you have to kind of switch to regulatory side, which you may not have experience in. Is there kind of efforts, and I think this is probably one effort, but other efforts by the FDA to kind of streamline that process and assist investigators? So I would like to share maybe a perspective from a successful IDE case that I had and totally understanding what Dr. Berg has shared. But I just want to share tips and points. And I'm not going to talk about efforts, maybe Dave or Sharon can talk about that. But tips that helped speed the process from a lab perspective, from my experience, were to talk up front with the FDA, to speak up front with the FDA, to help us understand. And I want to say that the actual, from the time the actual process started until it ended, I don't know the exact time. But it was, if from the time the pre-submission, and it was less than three months or something like that. But it facilitated and made the communication easier to continue to interact and collaborate like interactive review during a pre-submission phase. Sharing and understanding how that specific lab worked. And we had direct communication, not with the people to prepare the documents. But with the actual individuals who developed the assay. So even having them in the phone calls and the interactive review process to talk to us about the assay and how they did this, it helped bridge the gap because when we said things like, we want you to look at the agreement in a negative population or so on. We sent it in writing. It took a while. There were levels involved and differences in interpretation of the terminology. So from a bright side, I think this really helps reduce the time. You are talking about two different worlds that need to communicate. And yes, because it's not such, it's a very rare submission type that people will have to do in the world of in vitro diagnostics. So people don't have that experience. We are always open for helping out and reaching. I'm reaching from NCI. So I have a specific question for the sharing. He's speaking to the mic. Oh, he's on. He's on. He's on. OK. So the cell line is useful for the rare mutation. If you cannot find the clinical sample, sometimes it's valid, right? So used for the validation. So most cell line has a public database. They have no mutation. Is it valid to compare your SC result or some public database? So it depends. So it depends on the quality of the result in the public database. We accepted the reference material by the genome or bottle as part of our clearance for the next generation sequencing platform. But if for other cell lines you want to use with specific mutations that you are going to detect, but they are not from the well-recognized resources or databases, then you have to test your cell line with that mutation using the reference method or comparator method and then compare it to the result that your device has. Do we have any other questions? All right, thank you to our panelists. Thank you. And our next, we'll move right on into our next session, which is risk assessment. From FDA, we will have Drs. Jeff Seidman and Kelly Kelm on our panel and from NHGRI, Sarah Hall. And presenting first will be Dr. Seidman, who is in the Division of Molecular Genomics and Pathology within the Office of In vitro diagnostics.