 Pleasure to have Janet joining us. Janet, thank you very much. Janet has been one of the most progressive figures in life sciences over two decades, most recently as head of CEDR, where I think you get to hide a little bit from the public eye, which you don't get to do as the FDA commissioner is now a politically appointed position. And we have moderating this panel, one of the great moderators and a 15 year plus veteran of the USAIC and my predecessor as the MC, a great translational scientist from academia where he had an illustrious career at Harvard to Lilly where he ran an early development and research organization to a role leading the medical portion of pharma, the trade organization. So Bill, without further ado, I'll hand it over to you. Well, thank you very much, Andy. And I must say that you and Karun continue to do a wonderful job. I wanna welcome Janet, it's good to see you again. Thanks. It's always wonderful to see you. And so thank you for joining us. Janet is the acting FDA commissioner and needs no introduction. Janet, I was looking at your biosketch and I've just learned and maybe not so surprised you've been at the agency for over 35 years, but who's counting, right? And over these 35 years, you've been in multiple leadership roles and you've had a chance to oversee and actually witness a number of great developments in terms of therapeutics, including therapy for HIV, inflammatory diseases, which I'm sure you're very proud of. You're a rheumatologist and also cancer, including immuno-oncology, all the way to our recent developments in cell and gene and now nucleic acid therapies. So we appreciate that experience. We also know that the mission of the FDA is to protect the public health by ensuring safety, efficacy, and security of these therapeutics. So I think what I'd like to begin by asking a fairly general question, what are the biggest changes you have seen over these years at the FDA? And really in a sense, what are the things that you're most proud of? Well, you know, first of all, I would say of the organization itself, turning organization into a loosely structured confederation of scientific personnel into something that can, you know, take information and process decisions, lead, say, as Rick Pasteur is doing, lead in a field, drive fields forward, provide standards, stability, predictability, and so forth. And that can't be underestimated in its importance, although it's not very glamorous, right? So the building of an organization that is really an extremely high quality organization that has high quality outputs normally is very important. Although I did hear some of the last panel and some comments that perhaps, not every output is of the uniform quality, but we really do strive for that and we're continuing to try to make those improvements. So I'm very proud of that because without that kind of substrate, you can't get to the next level. What I'm working on now as another effort is to get enterprise-wide IT infrastructure and data infrastructure in place. And that I think will get the FDA to yet another level where we can automate a lot of processes and we can move to modern platforms and really let the scientists do science rather than a lot of the kind of busy work that we see right now. And that means moving towards structured submissions, data submissions rather than narratives and so on. But this is like looking toward the future. So that I'm very happy with and getting personnel in place who can actually operate these programs at a very effective level. Then of course the science has driven the scientific changes over that time have driven so many changes and have been so profound. I'll never forget my shock when I first started working with ICH and I was told, well, toxicology studies didn't look at bioavailability. We just gave the animals that medicine and the substance and just saw what happened, right? Without seeing whether it was absorbed or how it was metabolized or anything. I mean, we forget how far we have come and possibly that's because I go far enough back to realize where we were. But the science has just been driving during that whole time. I mean, when I started at FDA it was beginning of the thrombolytics. I got to preside over all the INDs for thrombolytics for stroke. And those were very scary and exciting times. And then we saw all the biotechnology drugs come along and then we saw the antivirals not just for HIV but say now we hepatitis C, say it's a curable disease, other virus illnesses can be controlled and so forth. And then of course the revolution that we have seen in cancer over the past 12, 15 years has been really astounding. So the science has come along and in concert to that we've managed to get more resources for the agency go through user fee programs and other programs so that we can build the science and match that science that is evolving on the outside. And we've strengthened our partnerships with groups like NIH, CDC, and of course, I'm very proud of what we've done in ICH and international regulatory harmonization over the past 30 years, which is something, again, I was talking to WHO meeting this morning and I really am pushing, we really need to move toward a single platform for requirements for a manufacturing and controls requirements for a drug worldwide. So we don't have all these versions all over the world and you can make a single submission and change a manufacturing process or a single submission change of specification without going to 50 different regulatory agencies. And I think that's achievable in the next decade. So... Well, these are all wonderful achievements and I'm sure you can go on and on in the previous panel. Of course, they did cite the advancements in science capability at the agency which I also agree has been remarkable. So quickly, are there any regrets or anything that you might have changed or would have liked to have seen evolve differently? Well, I think I've learned as a manager over the years, I think we all do and there are things we would have done differently managing people and so forth. Have we known what we know now back then in the day? Isn't that true for everyone? I mean, otherwise you really haven't learned very much from your experiences, right? So sure, looking back, there are a lot of things I would have done probably more effectively had the experience and maturity that I have today. But I did the best I could at the time in many different settings. So that's about all I could say. Well, that's quite good. So maybe the last point in this general part is you have a chance to continue to evolve the agency. I also learned from your bio-sketched that you are not only an avid, but experienced gardener. So thinking about it in gardening terms, what are the things that you would want to plant in addition when you have a chance to do that, to see it flower in the next decade, let's say? Well, I need to plant and cultivate data science. Okay, that's part of the scientific future, right? And we're just embryonically starting on that, but it's going to be so important in effective regulation going forward and managing the huge flood of scientific information and other data that we get. So we're starting that. We have a chief data officer and hats off to Amy Abernathy. Well, she was at the agency. She got some of this organized and started, but I'm gonna drive it forward. So that's something that needs to be done. I think the team science and thinking about, because now I think the day of, okay, what I call the randomized and do the body count, the empirical evaluation of therapies that era is ending and we need sort of, we need a totality of the evidence understanding of what's going on biologically. And we have all that basic science to add into the mix. But there we need a multidisciplinary team and we're trying to train people on team science. We're seeing crosses between devices and drugs and implantable device biologic living cells, right? And we're gonna continue to see that. And so we need to train our reviewers who are typical scientists. And many of them, they just wanna do their own thing. We need to train them on team science at multidisciplinary activities because again, that's gonna be the future. And that has been started. We're having seminars, we're having people come in and do trainings of different kinds so that people begin to learn how to work in that environment. If they don't, some people are naturally very good at that. Thank you, Janet. Well, let's go on. Of course, the question that is most on people's mind as we prepared for your fireside chat was of course, at a counter map. And so we will explore that. And then the other is really what are the lessons learned from the COVID-19 experience? Your efforts on operation warp speed, et cetera. So those are two main topics. If we have time, I'd love to, you know that I'd love to talk to you about manufacturing, about clinical trials and biomarkers. You know that. But let's see how far we can go. So relative to out of Kenameth, obviously the recent approval of the drug has generated a huge amount of interest. So that's a great understatement, okay? You know, obviously it is in some circles controversial. You're not a stranger to controversy. Obviously for many folks, it provides tremendous hope, a chance to potentially have a treatment for Alzheimer's disease. And for others, there's consternation and confusion about what was the process that led to this, especially when there's a broad label. You know, there is issue of whether the Pivotals really did provide the proof of changing the endpoints. And finally, an ad committee that voted unanimously against it. So it's not a matter of defending your decision. It's a matter of just for us to understand, for you to share the thinking process, how you navigate this very difficult decision. Because we start out by saying it's safety efficacy, right? And that balance is always very tricky and difficult to assess. Well, basically I think people question the effectiveness and the conclusion that the surrogate is reasonably likely to predict clinical benefit. So yes, there were process problems and this all occurred during COVID and so forth, but there were process problems that led to some of this confusion, I would say. Number one, the advisory committee was asked to vote on traditional approval, not approval based on a surrogate. And so they voted against it based on the fact that there was one negative trial and there was one positive trial that had been stopped for futility in the middle of it, okay? And they didn't feel that that was rigorous enough evidence. The ultimate approval was based on a surrogate endpoint of clearing amyloid plaque. And the last panel was talking about the pace of science and how fast science is evolving now. And one of the things I think that is evolving is the pace at which findings come out and development programs come out. And so a number of years ago, of course, the agency stated there was no biomarker that could, at that time would correlate with clinical benefit, but we've seen multiple programs since then where that has been evaluated and there's data available. So similar to like what was done with HIV, say, in some of the very early approvals on CD4 count and so forth where almost in real time that the data from ongoing clinical trials were incorporated into evaluation of that surrogate. And then some of the early drugs were approved based on that. This was a quickly, rapidly evolving situation. So I expect that the review memos, the supervisory final decisional review memos should come out in the next couple of days and be made available and allow the agencies thinking and as soon as they can get redacted, which should be within the next week or so, all the memos will come out, okay? So another process problem there was internal division for the initial approval, right? There were differences of opinion and therefore that wasn't, I think, that was brought out more in front of the advisory committee than would be traditional for the FDA to do. So that added to the confusion and controversy, but fast forward to now in this approval, which was an accelerated approval based on surrogate endpoint, reasonably likely to predict clinical benefit. My own assessment of this is very solid. It's a very, very solid accelerated approval has probably a lot more supportive data than many accelerated approvals we have done over the years, all right? And I think some more information will come out about that in the next couple days or weeks. So part of the confusion was due to the evolving nature of the science. Thank you, Janet. So among the kinds of questions that have come up would have been, does this mean that other drugs that lower beta amyloid could be approved based on biomarker data only via the accelerated approval pathway? It certainly would be possible as the agency, you'll have to, people have to look at the memos. There's an issue of magnitude, there's an issue of exposure response on the surrogate and the correlation with exposure response on the slowing of cognitive decline, right? And so magnitude matters and also safety and with the size of safety databases. The, this drug and like many drugs that have attempted to do this are not without their liabilities. And it does appear that the aria is related to the pharmacodynamic effects of the drug and therefore, you don't get one without the other potentially although not everyone gets Frank aria, you have to expect that people will, many of the subjects who are exposed to this drug will have that side effect. So there has to be enough of a database to look at the side effects profile and the benefit risk assessment. So some have wondered whether the FDA now has lowered the bar significantly for approval for therapies that don't exist for serious and life-threatening disease. So I gather from your previous answer, I think I know your answer, but maybe you could be clear on that. Have you lowered the bar? I've heard that for 30 years. I heard it when I proved, CBER approved beta-seron for multiple sclerosis so long ago. Okay, oh, that was only one trial that lowered the bar that we're gonna have a flood of inferior therapies getting on the market. We don't know whether that works. When Karl Pack approved several early HIV drugs based on CD4 and then eventually viral load, it was like the bar is lowered, we should have done mortality outcome trials for every single antiviral. Do you remember that conversation? That was bitter, fuck bitter. Yeah, absolutely, yeah. And so on and so forth, it goes on and on during the years, particularly around approval based on a surrogate. So I don't, this I think, as I said, is a very solid approval, this testicle performance of the surrogate was very strong in multiple trials, okay? So what people will complain about is the reasonably likely to protect clinical benefit. In other words, what is the correlation with the clinical outcome of interest? And I think you'll see the analyses that were done when they are released. I think they're very solid. So no, I think if the bar were lowered, maybe I lowered it back in, I don't know, 1989 or something when it is zero on proof, okay? You have not changed the bar. So really a question, and I think there's a question coming in from Chris Veebacher, relative to accelerated approvals. So do you anticipate any additional changes to that pathway in the near future? Or are you happy with the way it stands? It depends on what parties you talk to. I mean, some people want to do away with it on the external parties. And those are the ones who've been most vocal right now about this approval and how it's going to lower the standard and so forth, because they are really fundamentally attached to the paradigm that RCT is the only way, on a clinical outcome is the only way you can actually gain knowledge. And so that's one poll of the argument. On the other side of the argument, I think Rick Pasteur has been exploring different permutations of accelerated approval in workshops that they've been having and so forth that might modify it potentially slightly in the other direction and include other types of outcomes and so forth. So that means I think that likely we're not gonna see much of a change, but certainly there's always discussion of this. But fundamentally Bill, I think we have to at some point, the 50 year investment in basic science has to merge with clinical methodology and we have to stop just thinking that empirical evaluation is the only way of determining truth. It's very important and it made a tremendous improvement over clinical anecdotes in the 60s and 70s. It has supported a flowering of the armamentarium and a better understanding, but in fact, we don't do enough clinical evaluation. We don't really understand often dose. We don't understand target populations. We don't understand individualization of medicines. Most of clinical guidelines as Rob Kayliffe has pointed out our expert opinion. So you can't know that and say, oh, well this is the gold standard and this is the only way to do things. So I really think, I don't think that point of view over here has a tremendous amount of merit. I'm just looking at the time. It's amazing how quickly does time does fly, but let's get questions from a couple of people from the outside. So Chris, Veebacher, can you ask the question quickly? And then Janet, maybe if you could respond briefly as well, then we can get- I'm sorry. Yeah, I will. Hi Janet, it's great to see you again. The industry tends to think of the FDA as the regulator, but one of the things I learned when working with Bill at Pharma and my interactions with you is how motivated people are at the FDA to also make sure that new important drugs get to patients. And I think we sometimes forget that. And you've certainly tried to strike that balance between being a rigorous regulator, but also thinking about patients. One area that we've talked about this morning is ultra rare diseases. You know, where we've got just a handful of patients. It was the point made, could we even get them approved if we just show that they're harmless and not show efficacy? Accelerated approval pathways maybe one way, but any thoughts about how the FDA can help those that's obviously not just a regulatory issue here, but how the regulator might help those who are kind of developed treatments for these ultra rare conditions. Yes, well, I've been talking to Dr. Cavazzoni about this because it's becoming more and more of a problem. Okay, we as the FDA or anybody who's industry can't just look people in the face and say, well, you have an ultra rare disease abandoned all hope and we'll never get any treatments for you. You know, even if it's a fatal disease, it's too hard. You know, the two few people, that isn't right. And so that's a place where mechanistic reasoning may really play a major role. I mean, we really have to think about how we're going to do this. You have to admit, if you look back over the last, probably 15 years, the FDA has often been pretty remarkably flexible in some instances where they've been these ultra rare diseases that are especially very serious. In other cases though, I feel like we weren't as flexible as we should be at least initially and sort of, so there's certainly the leadership of CBER and CEDR are talking about this and figuring out, you know, we have to, we have to chart a different course. We have to take this seriously to figure out how we're going to do this. Thanks. Thank you. Let's move on to lessons learned from COVID-19 and there were a lot of questions about that. And clearly, because of the pandemic, there have been changes, you know, more interaction between the FDA and industry. We would say speedier reviews in some instances and faster decision making. So I'm gonna ask John to maybe ask a question relative to that. John Reed. Yeah, thanks, Bill. And Janet, great to see you again. I think I speak for all my colleagues when I say we hope that your current role as acting commissioner will be converted very soon to permanent official. Really, you know, so impressive, the experience and leadership you bring. You know, I think it's safe to say the world was very impressed with how the FDA stepped up during the pandemic to adjudicate regulatory actions with an incredible pace. So naturally the question arises, what would it take to keep that up and to be able to apply that now in a post pandemic era to other egregious life-threatening illnesses from a resource standpoint? You know, how much of the current resource devoted to the pandemic could you redeploy for other diseases versus how much additional resource would you need to really be able to do that with justice? Well, the FDA really didn't get any base increase in resources for COVID. We've got supplemental funding, which was like one time funding, not sustained funding. So I encourage when I got there in January 20th, I encouraged different center directors, higher term employees, right? And maybe we can, you know, bring them on because people had become exhausted. CDRH had, you know, CDRH just told me today they passed their thousand action, either supplemental change or approval or whatever for COVID-remated products the other day. So, you know, people are tired and they cannot keep this up. There was really people rose to the crisis. So if there were an area that really needed this kind of intervention, it would require infusion of people and dollar resources. For example, in cancer, the cancer program long ago when I was up at the commissioner's office got an infusion of people and resources and they got a salary bump for the oncologist of significant when you think of government salaries. And so Rick was able to not only run his program but these other very innovative programs he's running and he continues to run like Project Orbis where he's getting regulatory approval simultaneously around the world with, you know, co-review, collaborative review. He's doing a lot of patient report outcomes. He does a lot of outreach to the community and so forth. That was a fast turnaround as you well know of applications in cancer. That was all enabled to great extent by the additional resources that program has had put into it. Over the years, appropriated resources and this was primarily due to cancer communities lobbying to get more resources for cancer review at the FDA. So if there were additional areas identified such as rare diseases or something else similar to how we started the oncology program and begin to add staff and additional resources in I think you'd want to do that in another program and slowly build that program up so it could be more responsive. Thank you. Thank you, Janet and John. So the next question I'm going to ask Elise Reisen to ask her question because it's related to this whole issue of, you know now we had an experience where we had rapid or faster decision making. Well, at least will you ask your question? So Janet, just like others I want to thank you for your leadership over the past several decades and really driving innovation at the agency and just seeing the way it's progressed has been phenomenal I think for patients. So I'm going to make this one a little easier on you. What can we in pharma be doing to drive innovation faster to get drugs to patients faster? And maybe even did you see us do things during COVID that we should continue to do that we weren't doing before? You know, one of the things you did, you put together I think the community trial. If there's one thing I think you could do is support master protocols better. They are harder to set up their pain in the behind, right? You lose control, you lose some control on the evaluation of your asset. But once they're up and running, they can crank through and develop really invaluable data. And I think it improves the trust by the community that the evaluation was done in by a third party that had been doing a lot of evaluations in that area. So I think in COVID, except for recovery really and remap cap and a couple of the other master protocols that they weren't faster because they hadn't been set up. They had to get set up and that took quite a long time. Now they're recruiting very briskly, okay? And it's a cranking out data, but it's, you know but I really think that one of the lessons from COVID as you well know, what I think about this is all the academic trials that were going on none of them had any hope of yielding actionable information. They were underpowered, they were under enrolled, they competed with trials that could tell us something. And you know, there should be a goal in the future of roping all this in so that we have a concerted effort if we have another pandemic to learn as rapidly as possible what works and what doesn't work rather than just publish or write case series up or whatever was done. But to start that and to support that if the industry would support more platform trials like remap cap was able to repurpose themselves quickly because they were already up and running, for example and to start studying interventions in pneumonia. Thank you. Let's go on. So another point deals with how the FDA during this period had fit for purpose pre-clinical and CMC requirements used for the investigational COVID medicines. How do you see these kinds of approaches potentially being immortalized? And then I'm gonna ask Lalit Jha to ask a question which is related to it. Okay, why doesn't Lalit ask his questions? I don't totally understand what you're asking. Okay, so really it's the issue that during COVID-19 you really permitted fit for purpose approaches to pre-clinical data as well as CMC requirements. So do you imagine that some of these might be immortalized somehow? Well, I think many of the things that were tried during COVID, which was an emergency it's going to be we're gonna evaluate them all we're gonna keep some and some will go back. For example, I think to many people surprised televisits and certain using telehealth interventions and so forth worked out really well in a lot of cases where people were resistant before. So I think things like that remote monitoring which we've been pushing for a long time, right? And many other things certain distributed parts of trials and so forth may be kept, right? But there may be things once we evaluate them we find they weren't as successful. I think the in sessions on the pre-clinical and on the CMC were probably done with some reluctance by the regulators from my experience and so we shall see, you know how much those might be kept. Let's go to Lalit's question. Thank you. Thank you for doing this. As you know, during this pandemic one of the main thing about physical inspection of facilities I think has been greatly impacted. And I believe FDA has come out with some innovative solutions of remote inspections. So can you give us a sense of what your experience has been and how do you plan to scale up your remote interactive evaluations? Sure. Yeah, we did issue a report on what we call resiliency a report on how we are going to get back to it's on our website back to regular surveillance inspections post pandemic for all the different commodity areas. But yeah, we don't call them remote inspections we call them remote assessments or virtual evaluations or different things like that. In some cases we feel there's always a need for physical inspection and what we can augment that with many of these remote technologies. We have formed a council that ORA is heading and we have some funding and we're going to formally amongst all the centers work together to evaluate the different technologies that we use. I know you're not that interested in farms but we had people taking videos as they walked through the farms and they saw sometimes conditions that could lead to contamination of the food for example. So these things turned out they're sort of more distant reality type of things. These things turned out to be quite useful. And I think we will use them to augment our physical inspections or be substituted just as we're using record requests. Sometimes they are adequate instead of going physically to see the firm. And so we wanna look at our armamentarium of tools and see how we can extend our reach as much as possible because physical inspections are expensive and we're constantly, Congress is constantly unhappy with us, we are doing more of them. Thank you. Thank you. Andy and Karun, how are we doing on time? I don't. Well, since I'm in the next session I think this is much more interesting. So why don't you take five? Take five. Very, very good. So we do have a couple more minutes to explore maybe 20 topics, Janet. So maybe I'll pick one. Okay, so one is patient focused drug discovery. You have been a strong proponent of this activity. It's obviously very, very important. And there have been activities at the agency for the last almost a decade now. How do you think the agency has done it with that and the information it's gained? I think it's revolutionized things. I mean, when I joined the FDA it had reputation as a black box, right? That it was opaque even industry or people who work closely with it. Nowadays we've opened up to patients for medical products areas and hearing what they have to say. It has really revolutionized, I think, how we regulate the each center devices, biologics and drugs certainly reach out that way. And of course the oncology center of excellence has a direct link to the cancer patient community. And here's a lot from them. What has it done? It's had us focus on what's meaningful to patients. It has us focus on making sure that trials are not excessively burdensome so that you can enroll and people don't drop out. It has made us focus on patient reported outcomes and the validation of those outcomes because that's really what matters at the end of the day that the person feels better and functions better. So I think it's just starting to have an impact because now patients are getting deeply involved in all of this. And of course it's time consuming and it's another track that we all have to work on but I think it's really key. And I'm on the board of PCORI, the Patient Center Outcomes Research Institute and they have done a huge amount of research on patient centricity and how to meaningfully involve patients in every part of the life cycle. And I think they've made a lot of contributions as well and most of this has been very positive. So maybe related to that is the whole issue of the use of real world evidence in regulatory decision making. And I know that you and Bob Temple and others really have thought hard, long and hard about this. So what's your current view of this? Just for all of us to, I guess. Well, you know, my current view is it depends. Okay, question about real, about ultra rare diseases, for example, we've used real world evidence as the registries, for example, as the basis of approval of drugs for rare diseases. And we probably will continue to do that. And I was just talking to the Center for Devices, they're trying to get their real world evidence efforts together. But look at COVID, we had random RCTs, which are purportedly gold standard, reading out diametrically opposed results. Right, of interventions, use more or less in a similar way, you know, not totally inexplicable, but very difficult. And we had all these case series, anecdotes, all this stuff, completely wrong, just completely wrong. So I think for diseases that are complicated, we don't understand them very well, real world evidence isn't gonna work very well for efficacy, for concluding causal inference, right? Because we don't know enough, but there are a lot of diseases where we do know quite a bit. And I think real world evidence, often to extend populations, to understand real world experience, to extend, like I said, we often prove drugs, we don't know how long you should use them, we don't know who should take them, we don't know the doses, real world evidence done well can help us with all of those factors, I think. Great, maybe one last, maybe quick comment about a topic that I know you really love to expound about, which is manufacturing and quality in manufacturing, using sort of a risk assessment type of approach in order to do this better, maybe faster. I remember a time when you came back from a meeting and I just happened to be there, you were so excited about continuous manufacturing and understanding then all this put together quickly what your view is now on the whole issue of quality and changes in manufacturing approaches. Well, I think we're going to see a big change happening because I think the US government is quite concerned about all the shortages that happened during COVID, the fact that there's so much offshoring of most manufacturing, even of critical drugs and they're going to invest in any essential medicines on US manufacturing. And I think they will invest in advanced manufacturing techniques, not a traditional manufacturing. So I believe that that will give the whole project a big boost because there will be funding and is flowing into companies that are doing this as there's more and more people doing it will learn more about it, there'll be more equipment manufacturers who will be involved, there'll be more control and there's who learn about this and how to do it. And pretty soon, I think the field will become a field if you know what I mean. And really people will be able to use what they want out of that for their own manufacturing. So I think it's very promising. Often that the innovators don't wanna do this with their new assets because it's just another risk, right? And so what we've seen is we've seen people once they have a successful product and they need to scale up some where they may try advanced manufacturing technique because it'll be more efficient and they can produce more probably more costs effective too. But with your new assets, what you generally wanna do is get them on the market, get them through the development and on the market as fast as possible without running the risk of not being able to make them. Well, Janet, thank you. Well, we're at the end of our time. I wanna be the spoke person for everybody here. So thank you so much for spending time with us. It's been our privilege. You've heard already the thanks from the innovators, but we haven't had our patients to thank you and families and so forth. You've done an incredible job over the many decades you've been with the agency. And so I think for that, we can only offer a simple thank you, but you know, we owe a bigger gratitude, a debt for future generations. So thank you, Janet. Thank you for the questioners today and have a good day. Okay, bye-bye. Bye-bye now. Bill, thank you very much. Karuna, I'll hand it over to you to bring us into the penultimate panel. I think Andy, you should comment a little bit on this panel because this is- I wanted to and you can see it in my face. Just firstly, Bill, you're a master and you're able to take on such dicey topics with someone who we all respect with such a plumb. And so thank you very much for leading us through that discussion. And Janet's already left us, but there is a challenge when people like us appreciate someone like Janet because it creates the sense of self-interest. And while there may be some amongst us that have self-interest, I think that the praise that Janet's hearing comes from us as human beings who believe in a common goal. For many of us, we see patients. For many of us, we're scientists and we're interested in data-driven decision-making. For many of us, we have family members and friends, as you said, Bill, who are sick, who depend on not just the innovation that comes out of our industry, but the ability of agencies like FDA to accelerate that innovation to patients. And Janet's just done an amazing job. And if she were here, what I would say to her is if she's ever having a bad day, and I don't think any of us can imagine what a bad day would look like for someone who's holed up within the Beltway in one of the most politically divisive periods of the history of our country might have. I can't imagine what that would be, but if she's ever having a bad day, just to think about what her actions have meant for patients both in the United States where her decisions have direct impact, but really across the world, it's really quite remarkable what she's done. And so thanks for helping to bring out that story, Bill. Thank you. Thank you, Andy. Thank you, Bill. Thank you, Janet. I think she's not there yet, but she's gone. Can we have the slide please for the Paul? Yeah, the question is among the following, what you view as the highest priority area of innovation for FDA to promote? Pauling has started. You have 60 seconds. Hi, everybody. I'm a double Patel. I'm the head of research and early development at UCD. And it's my pleasure to do this portion primarily because Andy Plumper master of ceremonies is in the next panel. So he can't introduce himself. It's a great opportunity for me. The results of the last poll, I think has seen more diversity of this one than we've seen in the previous ones. We have three top answers. So I'll only say what the lowest one was and that was C4 continuous manufacturing. So Janet, the FDA needs, we want a lot from you as what I get.