 Good morning everyone, thanks for joining. I feel like I'm paraphrasing the airlines industry when I say we know you have many choices and how you spend your time and we're very grateful that you've chosen to join this workshop this morning and have prioritized this. This workshop is really intended to be a community discussion about what can be done to accelerate innovation. As you know the the National Academy's report that was the work of the committee on identifying innovation in pharmaceutical manufacturing. And that report stresses over and over again that even though the report was directed at recommendations for the FDA, it is really not going to be possible for the FDA to move the needle significantly on facilitating innovation in the pharmaceutical industry without the actions, the aligned actions of the entire stakeholder community. So this workshop is what can the entire stakeholder community accomplish together in order to accelerate innovation and bring beneficial technology forward in pharmaceutical manufacturing. So to that, given that the whole workshop is interactive, and we really want to hear from the community. I'd like to point out that we are using Slido and the Slido code. Hopefully you already saw the QR code that you can scan. But if you go to Slido.com. Thank you, Linda. The QR code and the number for how to join that question platform is up. We encourage you, everyone in the community to look at the ideas tab, the ideas tab has a field where you can enter themes for discussion. It's not word limited in the same way that the question and answer discussion is. So in the ideas tab, where there's no complete anonymity, right, you can use your first and last name initial for posting. But if there is a theme that you would like to have the community discuss. We encourage you to put it in the ideas tab and then others can weigh in on the priority for discussing that theme and of course it goes without saying really but I'll say it anyway that you need to be respectful in your language and approach towards all viewpoints in this interaction mode. So, with that, I'd like to give a little bit of a recap for what Linda has right so Linda's given us instructions in the chat for using this slide oh as well. So with that I'd like to talk about yesterday and some of the highlights from yesterday. The top has been structured so that really the first two sessions were on information gathering. So the first session on information gathering was about the technologies that the committee identified, and that are likely to appear on the horizon in the first seven years, and whether or not the committee correctly identified those areas where innovation is most likely to to appear in pharmaceutical manufacturing before the FDA. And then also really did the COVID pandemic accelerate the timeline for any of that innovation. Right, so we heard from several speakers are at Nurendra Bam about what innovation is already happening within their companies, and what the status is of whether that would be implemented. I think in general the speakers were agreed that the innovation that the committee identified was was pretty much a good set right that there weren't any obvious gaps in the in what the committee identified. And so we appreciate that that feedback. And then in session two, we focused on what existing mechanisms are out there in the stakeholder community that facilitate innovation. We heard from the FDA on the mechanisms that they use for innovation primarily the emerging technologies program, and what their plans are for expansion, and sort of the next version of the emerging technologies program. The speakers and Sarah Arden did a great job talking about the different mechanisms that are accessible to industry, and, and how the companies, or the perspective of industry and using those mechanisms, such as the, you know, guidance from industry, the one on one sponsor communications are guidance from the FDA, excuse me, one on one sponsor communications but then external partnerships and other means of more actively pursuing innovation. And then in a session three, we discussed where the gaps are in those existing mechanisms. And it would be interesting. When the community talks about those gaps. It's very clear that industry is pursuing innovation, and it's very clear that the FDA is acting to facilitate innovation through mechanisms. And so really the question is where opportunities to either better align incentives, so that the business drivers within industry to pursue innovation are better aligned. Or, I guess the value is understood, as well as the risk of innovating. And then how the FDA regulatory global regulatory really community can help align those incentives so that the risks are lessened when the benefit to the quality or the costs or just the consistency and reliability of the supply chain, you know, provides a benefit. So really, what can be done to get the risk benefit equation from an industry perspective in favor of the benefit and in lessening the risk. So I think the work of today is really to take that further, right, a lot of input from our speakers yesterday, some interesting questions for discussion, some interesting suggestions on what the community could do. So what came up over and over again, through different speakers and also through the community was this idea of having a group approach regulators with a technology in the pre competitive early stages, and talk about risk and benefits there, obviously the, the, what you lose by that approach is specificity because it's not connected with the ultimate drug product at the end. But it perhaps gains in a shared understanding a shared knowledge of how that technology might be appropriately applied in pharmaceutical manufacturing. So, with that sort of lengthy recap of where, how, where we started yesterday where we are now. I'd like to introduce Sally. Oh, first I need to go back sorry. I'm so glad Linda gave me good notes. I'd like to call up the Slido questions very quickly, and just level set us about what the community thought so Eric if you could pull up the Slido polling questions. I believe if you could go back to question number four is that possible. And I encourage the community if you did not vote. I believe the poll is still open right here. Okay, thank you so much. Well, a relevant question which of these innovations do you believe will have the greatest opportunity to advance pharmaceutical manufacturing. And there was quite a bit of support for processing intensification and also modeling and digital designs but obviously continuous manufacturing modular systems I suspect and is lower on the list just because it's probably a part of that process intensification and continuous manufacturing. And again with the advanced process control and automation. But it's interesting to see that all of these are viewed as as important but perhaps there are areas where specific companies or innovators have different interests. Linda's giving me guidance to pause a minute and allow those joining today to add their votes to this. So I'll give you that minute I looks like nothing's changing right now. So if we can advance to question number five. Thank you. The next few questions were really to what extent do you think it's possible to accelerate innovation and pharmaceutical manufacturing, either by the actions that are really more within the regulatory sphere. And, as you see the community believes that there is, you know, to some extent it is possible that innovation could be accelerated by changes in regulatory policy procedures practices or cultures. But it's interesting with the option of to a large extent. So, 65% of the population of the community didn't think that that is the largest contribution, right. You know, so to some extent that is true, according to the community. Right, so it looks like that stabilized so if we could go on to question number six. Thanks. Which type of regulatory changes do you believe can best enable innovation, right. It's interesting that workforce training currently seems to be more significant, a slightly, well I guess we don't know what the arrow bar is, but. Oh, okay, so that's moving as we speak guidance and regulations and workforce training. Really, it looks like a pretty decent split on all of the above. If we can move to question number seven. Okay, and this was interesting. It would be based on the attendees the participants in the workshop, and the large number of industry members, it would appear that the community believes that industry practices are really a significant opportunity to enable innovation. And so, to a large extent, the culture of the ability to enable pharmaceutical innovation, right, is in the hands of industry practices. And the next question please. All right. So which industry practices would be most impactful to enable innovation, increased recognition of manufacturing as a value driver and a greater accept willingness to accept risk. Really all of these are viewed as important. I think the poll is still open I encourage you to be using the Slido platform I got a side message from someone that says that the ideas tab doesn't appear to be working yet so I don't know if that's just because the polling questions are up. But. It's because the polling questions are often we wanted to review it with everyone, but once that the session starts after Sally, I'll turn it on for ideas. All right, great. Thank you, Linda. So it sounds like once we move to Sally, so I'll go ahead and introduce Sally so that you can begin putting your ideas in the Slido so Sally Romero Torres will be moderating session for session four is on possible solutions and actions and I'll turn it over to Sally to to lead us into that. Thanks, Sally. Thank you. Can you guys hear me. Thank you, Kelly. Can you guys hear me. Okay, thank you so much. Thank you so much. So, today, you know, after all those great presentations that we had yesterday. And, you know, where everybody was providing their point of view we also gave some opportunities to the FDA to provide you know to answer to certain questions that were in the report. We want to talk in session for about possible solutions and actions, right to some of those gaps or opportunities that we have identified. So the format of the session, it will be first a talk by the FDA that will be followed by a series of short talks it's going to be three short talks that we're going to be having. And after those three short talks we're going to have a community discussion, and hopefully it's going to be very alive and everybody's going to be trying to fight just to ask questions and to express their points of view. So the first talk, it's going to be, as I mentioned by the folks from the FDA, it's going to be done by Mr. Adam Fisher and Thomas O'Connor. And Adam Fisher is an associate director of communications at the FDA at the Office of Pharmaceutical Quality. And he's also a chemist at the FDA, and Dr. Thomas O'Connor is the director of the Division of Product Quality Research Office of Testing Research Office of Pharmaceutical Quality for Cedar at the Food and Drug Administration. Dr. O'Connor is the director of the Division of Product Quality Research in the Office of Testing Research and Office of Pharmaceutical Quality and he's a member of Cedar's emerging technology team, ETT. His responsibilities include managing research and testing products that answer and anticipate pharmaceutical quality related regulatory challenges through scientific approaches. The impact of the OTR research and testing is utilized to support regulatory assessments and policy development in areas such as advanced manufacturing, drug quality standards, characterization of complex drug substances and drug products and post-market product quality and public health issues. Tom is a co-author of several papers on emerging pharmaceutical technologies such as continuous manufacturing, 3D printing and the utilization of modeling and simulation for quality assurance. The ETT he has contributed to review of several regulatory applications utilizing novel technologies. He is the co-chair of the OPQ Manufacturing Science and Innovation Center of Excellence and is a member of the Advanced Manufacturing Working Groups within the FDA. Tom originally joined the FDA as a chemistry reviewer in the Office of Generic Drugs and prior to joining the FDA Tom worked at ExoMobil Research and Engineering where he held job functions in both process analytical technologies and process control. Dr. O'Connor earned his bachelor degrees in chemical engineering from the Cooper Union and a PhD in chemical engineering from Princeton University. So with that I would like to welcome Tom O'Connor and Adam Fisher. Thank you Sally so much for the intro. I am Adam Fisher. I'm the Associate Director of Science and Outreach in the Office of Pharmaceutical Quality at CDER. I do want to take some time here today to describe some of the actions we're taking to address gaps and pain points in the current regulatory framework. And I also want to start with an apology to whoever is advancing the slides here today because I do have a number of animated bullet points that will need to pop up. So I will be calling out the clicks as we go. Hopefully things don't get off track. Next slide please. So you've already heard about our emerging technology program earlier here in the workshop. A big milestone it was the 100th industry sponsored meeting. One thing that I do want to reiterate that Larry Lee mentioned yesterday is that you do not have to have a pending application to be part of the emerging technology program. You can be part of that program earlier in the technology development. Next click please. So because of that program and because of workshops like this we know that there is a rapid emergence of advanced manufacturing technologies. Click please. And we have efforts in advanced manufacturing to really drive toward this long held CDER vision of having a maximally efficient agile flexible pharmaceutical manufacturing sector that reliably produces high quality drugs. And that said, we recognize that the emergence of these technologies means that the regulatory landscape needs to evolve along with them. Click please. So we're reviewing the regulatory landscape and then we're working to ensure its readiness to accommodate the new technologies that we'll see over the next five to 10 years. Next slide please. So we're calling this initiative the framework for advanced, sorry framework for regulatory advanced manufacturing evaluation or frame. Dr. Coptia mentioned it yesterday and I will talk about it in more detail here today. We need a regulatory framework that provides certainty for stakeholders and is flexible enough to handle the technologies that we might see over this timeframe that I mentioned of the next five to 10 years. Next slide please. We thought it was important that as an agency, we understand innovations and pharmaceutical manufacturing, a bit better. Click please. So these workshops and the resulting report have allowed us to get a much better sense of what these emerging technologies look like, how they're going to be applied in pharma, and then most importantly, their impact on public health. Click please. We've also shared this vision in the paper on industry 4.0 that Dr. Coptia mentioned yesterday. I point out that this was authored primarily by Sarah Arden when she was still a member of the agency, not that long ago and of course Sarah gave a great presentation yesterday on some of the tools that are out there to stimulate and support innovation. I will just add that from my perspective, I think COVID-19 accelerated the need for manufacturing innovations and especially ones that are more responsive to rapidly changing demands and technologies that reduce our dependence on human interventions in the process. Next slide please. And because of our engagements of the emerging technology program and because of these workshops, we've now identified four technologies that we believe will play a major role over the next five to 10 years. Click please. The first is end to end continuous manufacturing, and we call it E to ECM. Click please. The next is distributed manufacturing or DM. Click please. The next is point of care manufacturing or POC. Click please. And then the final one is artificial intelligence, which everyone knows is AI. Now I want to explain a little bit more about how we're defining these technologies. Next slide please. Click please. So end to end CM is a fully integrated process in which raw materials or chemical intermediates are continuously fed in and then finished drug products are continuously removed. And most are familiar with some forms of continuous manufacturing to this point, which has been looking primarily at manufacturing drug products or drug substance, whereas end to end is the whole thing in one process. Click please. DM is a decentralized mobile manufacturing platform that can be deployed to multiple locations and importantly, within one quality management system. POC is actually a subset of DM that operates in close proximity to patient care. And this could include places such as hospitals nursing home physicians offices and the like. Click please and then finally there's AI, which can perceive the environment through data acquisition, interpret the data and decide the best actions. Next slide please. And so here's a very important thing to consider as we look at the framework. None of these technologies existed in vacuum. There are many advanced technologies that could be deployed together and for the four that we are focusing on that certainly the case. So for example, some DM will employ CM and some DM will be designed to operate in the CGMP environment and be POC. And for example, I would even note that you could have something in the middle bottom of this slide that uses end to end continuous distributed point of care manufacturing controlled by artificial intelligence. And this is not science fiction anymore. This is something that will be happening. Next slide please. So with this all in mind we want to ensure that we're taking a systematic approach to developing a regulatory framework, and we divided our effort into three phases. The first is building the foundation. The second is planning the implementation. And the third is setting things in motion. And we are now at the point where we are transitioning into phase three. Next slide please. We call phase one building the foundation, and this is where, based on our knowledge of relevant authorities. We brought all of the relevant OPQ experts together to assess the existing guidance regulations and statutory authorities to identify any gaps or pain points. So let me just pause for a second and define what I mean by gaps and pain points so gaps refer to the provisions regulations or guidance that govern quality assessment, or inspection that preclude approval of an application proposing to use an advanced manufacturing technology. Pain points are all the other regulatory challenges. For example, this might be ambiguous language, or lack of guidance on a specific topic, or just general lack of technical knowledge on a certain subject. So, let me give you some examples of things that we might consider gaps and pain points. Next slide please. So, one might be the applicability of a regulatory terminology that does not or may not account for emerging technologies. The second is potential holes in drug application requirements. And then finally, the ability of these technologies to comply with current regulations and standards. And now we need a framework to address these gaps and pain points. Next slide please. So phase two of our effort focused on making recommendations to address these gaps and pain points, and also planning for the long term implementation of the framework. So during this period we conducted an in depth impact analysis to inform all of our potential recommendations. And what I mean by that is instead of just looking at the gaps and pain points for new technologies, the impact analysis looked in two directions that is it also looked at potential changes to the framework could impact existing technologies, because clearly we don't want any unintended consequences from something that we're trying to do here. And this view enabled us to come up with a series of preliminary recommendations for the framework. Next slide please. So phase three, this is where we are now and this is going to be a multi year effort that we begin by explaining what we're doing and also asking for help. So first, we're increasing our public outreach to share information and provide visibility into what we're doing. I hope it's obvious that that's what I'm doing right now. As I speak, a second, we are going to gather input from the public on the gaps and pain points that we've identified to further inform our thinking. And once we've had an opportunity to understand the issues and leverage our science and policy experts will begin implementing different components of the regulatory framework. And once of our outreach will be public white papers that will share the regulatory gaps and pain points we've identified, they're going to be released for public comment. And so you can expect to see white papers on these gaps and pain points in the not too distant future. And we plan to take the public comments and then post final versions of these white papers after we've taken all input into account. And these white papers and the associated recommendations that come from them to address the gaps and pain points will inform an overall internal Cedar frame roadmap that will be the thing that we follow to make sure that we realize this vision. Now keep in mind that everything we do, including related to the framework is built on a foundation of science. And so now I'm going to pass this over to my colleague Tom O'Connor to explain how we've built a scientific foundation to support advanced manufacturing. Tom. We're having some issues hearing you. We're having some issues with, I think, your mic. I think in the meantime, you might need to advance one one slide further. Tom, you might try at the bottom left of zoom making sure the correct microphone is selected. We noticed there wasn't any audio coming through at all. So it may be a microphone issue. But in zoom and the bottom left next to your mute button, there's an up arrow, and there'll be a list of microphones that are connected to your computer. So it might the wrong one may be selected. So maybe while Tom's trying to get online, I can just give a brief introduction to the science and research element of OPQs and Cedars actions here. And so I think it's important not to forget that the R in Cedar stands for research. As I mentioned, science and research really forms the foundation of everything that we do as an agency. Could you click on the slide? Hey, hey Tom, we could hear you through your microphone. We just heard you dialing in so your microphone may be active. If you want to try on muting and trying again. Hello, can you hear me now? Yes, we can hear you perfectly. All right. Thanks, Adam. I didn't want to put you on the spot there. All right, over to you Tom. Oh yeah, yeah, so thank you. Sorry, I apologize. I'm not sure what happened. But yeah, yesterday, you know, there was a comment about what we mean by, you know, science and risk based and, you know, OPQ is always valued and Cedar, right, the R in Cedar, the importance of science. We actually have dedicated staff, laboratories and facilities to really support that. And that science really enhances the FDA's capacity for decision making. And OPQ, you know, that's focused on drug quality. The next bullet, please. And we're talking about, you know, Adam's slides thinking about frame. Another thing where our science is very important is helping us to modernize regulatory pathways when there's emerging technologies that could be new drugs. In this case, new ways to make products. But that's also very important. We also use our science to address regulatory and scientific issues that are mission critical. So those are the issues that we're facing as of today. But, but then there's also the forward looking anticipating to make sure that we're ready to address the issues of tomorrow. And that's a kind of part what we're doing now. And that's coming to play during the pandemic came to play during you know, the current issues with nitrosine means heparin before that, you know, we've always been have that capacity to use the science to help us address these public health events. And now we're kind of turning that to to advance manufacturing. Next slide. So we've been actually spending the last one ETT stood up around 2014 2015. We realized that we needed a new component to our science program that would support the applications we were kind of expecting to see in the future that we were starting to get engagement with industry. And at the same time we start up some manufacturing science research programs. Then a couple years ago we got a more directed funding and allocation of resources to support that program. As part of that we developed a series of research plans that are now active in several different areas. And all of those is a cat capacity in things like novel manufacturing methods. So it continues manufacturing three printing things like precision analytics, high resolution mass spectrometry is an example. We feel this is really important to help us, especially when thinking about advanced manufacturing for complex products, you know the analytics and important piece there. And so as we look at the project portfolio just to give you some sense of what we're currently working on we kind of group projects into these different areas based on research plans of we have a group of projects around novel manufacturing methods is mostly small molecule focused. Again, we have another large active projects in precision analytics. And then we have a series of projects that are around the bio manufacturing space and advanced manufacturing for biopharmaceuticals. Some for emerging therapies and kind of cross cutting we have a series of process modeling and I would say AI machine learning projects. And we've part of the developing this capability we've actually stood up a computational lab that will kind of compliments our experimental laboratory facilities. Next bullet here. And just in the last few years as we set up these research plans is these projects produced over 65 internal reports and publications and these internal reports are things that are going directly to review teams or support a project for a sponsor meeting. So they're very impactful outputs. Next slide. We realized that this is talked a little bit about what we're doing internally but realized that this is really a community effort and we realized we couldn't make the advances we wanted to in our science program without collaborating with outside experts. And because of that we stood up a number of different opportunities, we leveraged the FDA regulatory science for agency announcement, as well as OPQ initiate some focused grant opportunities, so that we can really leverage the expertise in the academic and some industry companies. And over this these are projects that really represent again this last few years, where we've had some dedicated resources to support these program, and just want to kind of group them into kind of some of the themes and again you'll see some of the common things around smart manufacturing. Again, some novel manufacturing methods, PT group on process modeling simulation, and also one on training training is another big component of what we're trying to accomplish through the science program. Next bullet here and then this is accounting that was done this spring you know these projects again or just a couple years old some of them are just started and they'll produce more and more reports to advance the scientific body scientific knowledge around these technologies that we can then apply to help support our decision. Next slide. Yeah, first bullet please. Yeah, so what have we actually accomplished or learned from these programs so the research programs actually directly support the feedback and application assessment for over 10 projects. I think Larry you saw Larry mentioned yesterday we have like 12 application approvals for that program so the research is directly supporting a heavy percentage of those you know greater than 80% or so. The projects are directly being supported by the research, which means that either we're doing a study to support that review or yes and me from that research is being added that review team to address certain application issues. Next, policy and guidance development. So informing the q 13 is an example. You know the FDA draft guidance and our experience 2019 was very focused on small molecules, soluble drug products. That's what that guidance is focused on. The CHQ 13 is a bigger scope whose drug substance includes large molecules. And we've had a lot of engagement to the ETT and kind of pre pre application space and actually have a couple approvals some of those areas now. But the research program, you know complimented that provided a lot of knowledge to support you know expanding the scope of what we could publish harmonize as a guidance. And of course supporting frame, you know, I think it underpins a lot of decisions and a lot of the thinking that went on. You're during phase one and phase two and will certainly support it going forward in phase three. And workforce development. I think Mike, you know highlighted one of the accomplishments reason accomplishment from the ETT was graduating continuous direct impression from ETT, you know focus thing to moving it to more of the regulatory regular review channels or assessment channels, I would say processes. And to do that, we had to train the staff that was going to take on these these new applications. And we did that through a collaboration so you know, part of that was we funded external partners external experts to develop some training material training classes that provided the technical knowledge, and we complimented that with our internal training, where the lab and these partners with assessment offices, develop case studies and hands on training that were more directly applied to apply this knowledge to do what we you know the day to day tasks of an investigator or assessor. And that helped, you know, make this accomplishment, you know happen, as far as graduating the CDC. Next slide. And where we're going from here, I think it's a really exciting development, you know, we are currently constructing a research manufacturing pilot plant that will be located very close to the white oak FDA campus. And this is really going to increase our capacity generate knowledge and train FDA staff so when I think about this facility designed to be modular flexible, really focusing I'd say on integration integration can mean equipment can mean manufacturing, as well as automation, thinking about integrating the all the modeling efforts that we've invested in, integrating that with the actual processes. And training training is going to be a big, big focus here. This facility has dedicated train the resources facilities to really support that workforce development. Next slide. And we're going to continue to make investment in the research programs where we need it in the kind of growing areas of advanced manufacturing. We've awarded five new collaborative projects, just this September. Again, focusing, I would say if I looked at the projects that are funded, be thinking about kind of industry 4.0 themes there, as well as supporting some of the social science and data science around assessment, quality management of charity. Those are big programs that Mike mentioned yesterday, and we're kind of funding some projects to advance some of the thinking around that too. And next bullet and continue in alignment with the emerging technology program and frame you know our research product development science is really mission driven. We really need to support the decision making at the FDA. So we want to make sure we close alignment with those two programs and support them the best way we can. So just some closing thoughts. You know I think there was a comment about you know strengthening the Cedars expertise and innovative technologies and we really think our science program is one way we do that we through developing SMEs, as well as through training. Next bullet, we realize is something we can't do alone we really want to leverage and collaborate to advance the science. So we do that through external collaborations, but I think maybe there's other opportunities. We're really excited about our new infrastructure coming online I think this is really going to help grow the program, increase the impact we're able to deliver for OBQ and agency and the community at large. And then next slide. And again, just focusing you know we're going to continue to make sure our programs are focused on the mission at the FDA and supporting this, and hopefully making the change right help and do our part to help try this. So with that, I conclude our talk and we look forward to discussion later. Thank you so much. Thank you so much for for this great presentation and for your leadership. It's definitely exciting times at the FDA so we're all looking forward to see what's a product of all these investments. So I'd like just to put a little bit of like a, like a, like a grain of stand, right in people's minds right now just to keep on cementing the ideas is that, in my opinion, like this is specially needed right now because from 2009 to 2019. We have so a doubling in specialty drugs and specialty drugs require more advanced controls and more advanced control strategy so just we should keep in mind that whenever we're talking about the need and the business need for advanced technologies. So with that, let's move now to the series of short talks that we're going to be having. And then for this session we will have Kevin Lee, who is the Institute Director of Nimble will have Fernando Muzio who's a distinguished professor at Rutgers School of Engineering, and we will have Julian Sanders Schmielder and Stephen Colver from the Duke Margolis Center for Health Policy. Let's start by introducing Dr Lee. Dr Lee is the core professor of chemical and bio molecular engineering at the University of Delaware. He currently serves as the director of the National Institute of Innovation in manufacturing bio pharmaceuticals. And he previously served as the director of the Delaware Biotechnology Institute. Dr Lee received his bachelor degree in chemical engineering from Princeton University, and both his masters and his PhD in chemical engineering from Caltech. He also completed a postdoc in Caltech biology division and spent several years at the Biotechnology Institute at the et age in Zurich, Switzerland. He was one on the faculty at Cornell University where he held the titles of Samuel C and Nancy M Fleming, chair professor, professor in the School of Chemical and Bio Molecular Engineering, director of the Cornell Institute of Biotechnology and director of the New York State Center for Life Science Enterprises. He's also a fellow of the American Association for the advancement of science and of the American Institute for medical and biological engineering. His research expertise in systems and synthetic biology applied to farm biopharmaceutical manufacturing, as well as in the diagnosis and treatment of Alzheimer's disease. So thank you Dr Lee and the podium is yours. Thank you very much and I certainly want to thank the workshop organizers for the opportunity to address all of you. Just as a small disclosure at the bottom I think it was referenced. I do help lead nimble and that is sponsored by NIST and I also want to in that context reflect that my perspective that I'll share really comes more in the bio side of things for the larger molecules. I have a little less expertise and visibility understanding in the context of some of the smaller molecules. What I'm going to do on the next slide is kind of reiterate a little bit, some of the points that I heard yesterday that resonated with my perspective and then use that as a chance to make some perhaps bold suggestions and proposals. The goal that we were given in this session for all the speakers is to stimulate discussion on where the community might go from here so the first kind of point here in red is that while I think there's a lot of different stakeholders in our ecosystem broadly. And each stakeholder has different perspectives. There really is a common purpose across the entire ecosystem, whether you work in the regulated industry, whether you work for the agency or whether you work for other organizations. And in my words, it's some version of ensuring patient access to a supply of medicines to enhance our health and well being and you could put in the qualifiers of safe efficacious reliable and so on but it's really about patient well being and that that slice of apple pie is meant to recognize that I think we're all on the same team. So on the next slide. The evidence for that. And I did not cherry pick these I literally just went to Google and pulled up five companies that came to mind and and googled what their mission statements were and took it from their website so the Pfizer one of course talks about making the world a better place at at markets to improve the health and wellness of people. Amgen is striving to serve patients by delivering therapies that restore health or save lives BMS is to deliver innovative medicines that help patients GSK preventing and treating disease and keeping people well so you know I think many of the companies are well aligned at a high level about what their goal is and their mission is on the next slide. I took some language from vendors and suppliers, again just pulled from sartorius and millipore Sigma. They also reference in their mission, enabling the development of new and better therapies more affordable medicines improving health and life worldwide so I think it's fair to say from the industry side whether you're directly in the regulated industry or work with closely with the regulated industry. There is broad alignment on what we want to achieve together. And the next slide is some texts that I pulled from the FDA website so at a high level the FDA self stated mission. And it was to ensure safety, efficacy and security of drugs biological products and medical devices, and something that frankly I had not actually taken the time to study before two nights ago, was a statement that the FDA self declared is responsible for advancing the public health by helping to speed innovations that make medical products more effective safer and more affordable. The FDA mission Center for drugs of course has their own mission which is around ensuring safe and effective drugs that are available to improve the health of people so again I'm just trying to recap at a high level that I think we all come at wanting to solve at some basic level, the same kind of problem. Next slide, then I want to take us to thinking about what the current situation is, and advanced manufacturing which I put in quotes here, because I think we just heard a great presentation from Adam about a framework for thinking about advanced manufacturing at the agency, but I think there's still a diversity of thought and what constitutes advanced manufacturing but I would argue advanced manufacturing approaches are typically not limited by the technology itself. I think the risk is a business risk around adoption of those technologies and it's a perhaps a broad over generalization but I think a lot of the technologies that we hear about are things that can work. The science is there, the technology maybe needs to be matured but it works, but the reason we don't see it adopted as rapidly as one might hope is because of business risk around adoption. And that really that business risk is tied to speed to market being critically important to companies. So that adoption of a new technology or a manufacturing technology is going to increase the risk associated with getting that medicine to market. And so one could argue that there is very little or in some cases perhaps no business incentive for new technologies to be implemented in the manufacturing of these medicines in today's climate or today's situation. And the fact that we have a very fragmented global regulatory environment raises the bar, even higher now there's been a lot written and discussed yesterday and on, you know the business risks, and why we have that situation. But I think that's the reality. So on the one hand, I think we can think about what the agency can do to help encourage and position itself to be ready to respond to new technologies and I think it sounds like they're making incredible investments and have put a primary emphasis on that. But at the same time, I think there's a real problem here that the the business side also needs to find ways to be incentivized and I think some of the poll results kind of captured that. And the FDA definition of advanced manufacturing that I pulled from their website is it's a collective term for medical product manufacturing technologies that improve drug quality address shortages and speed time to market so you would think that things should be aligned from that perspective. So what do we need and where do we go. The next slide talks a little bit about the FDA's perspective on advancing health. And what I think in my anecdotal experience is are some examples of things that are working well, and then some of the challenges. So I think some of the things that are working well, I think there's a lot of really positive messaging coming from the podium and from the leadership and thought leaders at the agency around this. I think there's a real genuine willingness to partner and I think we've heard now a number of examples of that this morning as well as yesterday. I think those are all real positive messages. I think the agency has been engaging with public private partnerships to advance their understanding and build relationships. We've seen that in nimble through other participation and active listening sessions with us participation on projects to advance scientific research and we just heard Tom account or talk about some of the exciting things are working on in that space. I've been established I know credit is with a number of organizations, I think access through the ETP going through the ETT, I think, been very generally well received, and the data supports that and I think the opportunities to engage in consortia approaching through shared test beds and so on, is a highlight that I want to echo in my time here. I think there's a number of challenges though that also emerged I think there's a willingness to partner, but I would argue there's a lack of resources and bandwidth to engage at the level that would have the kind of impact that we all want to achieve. I think attorneys at various organizations would agree that, while the science and the programmatic people want to engage. That's not always the easiest thing to engage with with the agency or frankly in some cases the federal government generally. Those I think are solvable problems. And while there are a number of mechanisms in place to engage with the community advance the interest and advanced manufacturing that experience with some of those mechanisms. Sometimes fall short whether it's application reviews, where the messaging from the podium is not well aligned with some of the questions and that people get back in the industry or responses to reviews on BAA applications etc I think. I don't think there's any large organization, sometimes there's opportunities to improve. And in our current system is one where I would posit, and it's a bit of a forward pushy statement that reviewers may actually be dissuaded from supporting innovations that they're not familiar with when they see them in applications, because the reviewer has everything to lose by pushing and allowing a technology to move forward. And so that that's not an ideal situation. So what what can we think about doing on the next slide. I think we need community wide action. I think organizations and individuals have to actively engage in a sustained effort to help realize the change that we all see. I think it's not good enough to say there are hurdles to innovation and talk about the hurdles. We have to go and attack and do something to try to clear those hurdles I think the agency has indicated through some of their work that they're trying to get ahead of that and do some of the things that need to be done but we all need to be partners for change. I think our industry matters to a lot of us and to all of us and our access to advanced manufacturing capability matters, and I think us leadership and competitive matters. And so the opportunity is there to address everybody's mission to bring these medicines to patients. And what's really frustrating is it's not even the technology in many cases it's something beyond the technology. So here's some nuggets of some ideas that I put as on the next slide as policy opportunity so they're not necessarily things that people in the agency could necessarily do themselves. And I realized when I put up policy ideas, I limit the ability of federal employees to comment too much but they're not active policies per se. The first that I'd like to throw out there is to increase appropriations to the agency to facilitate the headcount necessary to more actively engage the community on advanced manufacturing adoption and implementation. I think it's a large agency it's got a lot of demands on its time. The stress on people I think in the agency over the last year and a half is just over the top. And user fees are one ways to increase revenues but I think you need to look at baseline opportunities to grow the research activity and grow interactions with public private partnerships and be out with the community even further to get the headcount necessary so I would argue there's a real need for more resources. The second idea I'll throw out there and these are not mutually exclusive is to consider tax incentives for products or processes that adopt advanced manufacturing approaches. I think this can help a whole variety of companies that can help the, those bringing innovator molecules to market I think it can, it could help those that make generics or biosimilars I think it could help those that are in the contract manufacturing sector. And then the third again not mutually exclusive is to think about, you know is it possible to have an extended period of exclusivity for products that are first to adopt advanced manufacturing approaches. To encourage the innovators to debate the business benefit of new technology relative to the risk to timeline. Maybe it's going to take me three more months to get to market. If I take a new technology approach, but in doing so maybe I get an extra year of exclusivity. Now, there was an idea posted in the ideas on Slido that I saw that I thought was really interesting which is, maybe, maybe it's a question of like a new regulatory pathway, like breakthrough status status. Maybe there's a way to think about, you know, an approach that relies on advanced manufacturing having some impact on review and status for that application. I say all this knowing that defining advanced manufacturing is non trivial if you think about it from a policy perspective I think it's a little easier for us within the community but how do you get people on Capitol Hill to think about how to define advanced manufacturing so it's not just a, you know, a Windows update all of a sudden is an advanced manufacturing solution. You know how do you think about that. Those are some ideas on the next slide. I was my last slide I think I think it's a community wide action so what what can I do. Well, I think nimble can commit to hosting follow up workshops to this one to continue the discussion I think we need organizations to be willing to engage. We need to ask how often we need to have those discussions and what do we want to accomplish and over what time, but you know I know as the National Academies study has finishes and as people think about moving forward. Again, it needs to be a sustained meaningful discussion going forward. I know that I'm willing to help advance thinking around relevant policy action so happy to take that. I'm leaving some blank bullet points for I'm, I think I and separately nimble are happy to do more, but we want to have a conversation about what we can do and what makes sense and so want to leave the door open to other ideas that we're certainly willing to engage with in the community and engage in other public private partnerships and other consortium other organizations to try to advance the needs of the industry so with that I really appreciate the time and look forward to the discussion. Thank you so much. Dr Lee, I think that it was in a very good presentation and I love the fact that you highlighted that highlighted that it's not so much about technology and most of the cases it is about the business risk. I think that we should talk a little bit more about that during the community discussion. So with that, now we're going to be moving. So let me introduce the next speaker, the next speaker is Dr Fernando museum. Fernando is a distinguished professor of chemical and biochemical engineering at Rutgers University. And for the last 30 years. He has been working in pharmaceutical product and process design and working on continuous manufacturing powder mixing powder flow segregation compression mixing and flow of liquids and suspensions. He is an author over 300 peer reviewed scientific articles and book chapters. He's a frequent participant at the events and in 2010 from from 2010 to 2014. He was appointed a voting member of the FDA committee on pharmaceutical sciences and clinical pharmacology. He is the director of the National Science Foundation engineering research center on structure organic particle, particularly system. And Dr Musio is also the director of the rockers, Jansen internship in advancement of factoring and the principal investigator of major FDA research awards, focus on material properties, sensing and process control in continuous manufacturing. Dr Musio is also the chair of the faculty committee of nifty. Dr Musio is also the president of integrity continuous manufacturing systems is a choir of comprehensive consulting services in continuous manufacturing and the chief scientific officer of acumen biopharma. So with that I'm going to leave the podium to Dr Musio. Thank you so much. Can you hear me. Excellent. Thank you very much for the invitation and I'm honored to be here and I hope I am able to contribute. Let's go to the next slide please. Here's my message I want to give you the message up front. I'm going to try to be very specific in this talk. I would like to try to provide actions that could facilitate innovation in the advanced manufacturing space, particularly removing roadblocks. I thought it would be a good idea to maybe focus a little bit on what I think is our best established success in the space which is continuous direct compression. I think since I think it's easy to argue that this is a successful implementation of advanced manufacturing. Maybe we want to spend a little bit of time understanding how it happened. How did we get there. What did we do that allowed us to develop a new manufacturing method that now is adopted commercially and more importantly perhaps once we understand how it happened, can we make it happen again? What does it take to replicate the process of going from an idea to a widely implemented methodology? What would be the roadblocks that we face? And then based on that, how do we enable ways to overcome those roadblocks? So I'm going to take a very specific view that enabling widespread adoption of advanced manufacturing methods is a catalyst for then other innovations to occur. So next slide, please. So again, why do I say this is a clear success in innovation? Well, first of all, there are multiple FDA approvals of products manufactured this way. More than that, it has become the default first choice in implementation of advanced manufacturing methods for solid-dose products. Based on my personal communications with equipment companies, more than 60% of all of the ongoing development projects in the oral solid-dose space in continuous manufacturing are continuous direct compression. There are dozens of projects innovators, at least 20 companies probably more than that. There are six, at least six established suppliers of integrated technology, meaning you can go to all of these companies and buy an integrated system. You have to then spend time and effort making it work, but the reality is that as a technology sources, there is an established community. I might be forgetting one or two, in fact, but this is by my last count. So in addition, we see already that the implementation of continuous direct compression is moving beyond brand-based pharma, and it's beginning to go into OTC products and generics. There are also, and there have been for many years, lines available to support development of multiple universities and at CMOs. And perhaps the most significant indicator is that, as was indicated yesterday by my copcha, CDC graduated from the ETT roaster is no longer considered an emerging technology because it has already emerged. Which I take it as a badge of honor. Next slide, please. So how did it happen? Because it's easy to think it was inevitable. It's easy maybe to look back and say, okay, it took very long, but it was always going to happen. I don't think so. I think that we could have faltered along the way many times, and I think that it was a combination of foresight by the part of the FDA. There were a series of fortunate circumstances where the funding was available throughout the development cycle. That's where we are. And there were people in industry that decided to take a step forward, mainly based on faith and the belief in their own technical expertise. But again, it didn't need to happen and maybe it wouldn't have. I can tell you personally from my very personal perspective, I know that I'm going to miss many other contributions, but I was trying to advocate doing this for a while between 98 and 2002, for example, and successfully at the time in those years. I was proposing and a number of people in my team were proposing doing this, and industry was telling us that it wouldn't happen, that FDA were never going to allow them to do it, that it just wasn't feasible. Next slide, please. Interestingly though, Merck actually had built a partial implementation at the time. This is not a photo of the Merck system. A similar system we put together, but it kind of looked like this couple of feeders going into a blender, examining continuous gravimetric feeding, continuous blending, looking at results. So there were some early efforts, there were other early efforts besides the Merck one happening all while companies were not deciding to move forward. Next slide, please. So then something that to me made a big difference was that Janet Woodcock and HS Hussein publicly endorsed the concept of continuous manufacturing of solid dose during a camp meeting. I think this was a 2002 in the Brunswick. Next slide, please. That endorsement, which was also incorporated into the BAT guidance, acted as a catalyst. There was a change in attitude. There was interest suddenly in doing this. So camp awarded some funding to MIT to start experimenting. And at the same time, we were able to form a consortium at Rutgers that included Merck, Pfizer, Apothex, and GIA. And we started working on continuous blending. And that's a picture of the early version of the GIA inclined blender that was the main thing that we were looking at at the time. Next slide, please. So then we got the ERC funded by the National Science Foundation in 2006, and we made a strategic choice. It was a choice to implement continuous manufacturing and we decided to implement continuous direct compression at Rutgers and continuous regulation at Purdue. And we implemented also lines at University of Puerto Rico and we had input from NJIT. There were 40 companies that came on board. Overall, we're probably spending the order of $50 million in continuous manufacturing in the decade between 2006 and 2016. The lucky circumstance was we had access to that funding. Yes. And so the picture shows what I think might be the first complete implementation of feeders, a blender, a mill, a tablet press, PAT, and closed loop control. And this early line, this obviously this academic style line was already up and running around 2008. Click again, please. Next slide. At the same time, we also started working on modeling tools. We partnered with PSE, we started building models, we started creating material property databases. I would say FDA joins these ups almost from the beginning. I think FDA came on board around 2007 and actually participated throughout the decade. People from FDA came to our meetings, provided input, encouraged researchers, actively provided guidance as to which things made sense and which ones didn't. It was very good to have a forum where we could openly discuss academics, industry and regulators, basically talk about what we needed to do. So next slide, please. So then the other thing that I thought was a major step for us was around 2011, J&J came along and said, okay, we would like now to develop the GMP version of these. And we formed a partnership with multiple equipment suppliers to create what at the time was called the Inspire line, which had catering feeders, a glad blender, a co-mill, and a FETI tablet press. At J&J they implemented with a different tablet press, but a very similar concept. And this received the level of support needed to create this line, the line that you see here is the line at Rutgers. There was a very similar line built in J&J, and there was a lot of back and forth, and we actually focused on developing the process for a commercial product, which was Presista, which was approved by FDA in 2016. It was the second product approved by FDA, but it was the first batch to continuous conversion of an approved product. Next slide, please. Since then, many other companies invested in collaborations, both at Rutgers and at Purdue and at other universities, as well as at the contra manufacturing sites, at sites outside the US, in Austria and in the UK, for example. But the other thing that was absolutely important, once NSF funding was over, and we were working on basically with industry, FDA continued to provide support, FDA continued to engage in the process to identify the gaps to provide funding to continue to move forward on implementation of process control and understanding material property effects on implementing methodologies for real time quality control. There was a significant amount of resources available in the last five years, which was very critical to getting the knowledge base, and also providing the confidence to industry that this is for real, that this is a long term choice, that we will make it happen, and this is a point to maybe stop for a second and realize that all of this needed to happen for us to be now saying that, okay, CDC is an established methodology that we can take out of the emerging technology list because there are other things that need to emerge. Next slide, please. So one went right. If we want to replicate success, maybe we can figure out on what were the key features that made this possible. So we, I would say, had a number of things that don't always happen. One is that the academics were aware of what the problem was that needed to be solved. And what motivated this whole thing were quality issues caused by batch blending. Yeah, when we started doing this, 20 years ago, the quality problems associated with batch blending of powders and being able to characterize blends and understanding what the state of the of the material were actually quite difficult were at the beginning, maybe of the implementation and continuous feeding continuous blending was designed to remove that problem altogether we were no longer going to have 500 kilograms of powder in a bucket. Okay. The second thing that went right. If the provided an early statement of regulatory support and a consistent statement of regulatory support throughout the effort. And the most perhaps the most important third factor was that funding was available across the entire technology lifecycle. There was money for early conceptual development. Yes, there was money available to support commercials can implementation. There was money to do multiple demonstrations of the technology. And there were early adopters that were willing to make the leap of faith and make it happen and provide work out examples of how this happens. So next slide please. There are some blogs that could we could face to replicating the success of continuous that a compression. Well, simply by logic extension of what I just said. There is a lack of share awareness of what are the manufacturing problems that need to be solved. I would argue that the technology dialogue between industry, the agency and academia is rather limited. I mean, we speak in some forums with big ones in a while, and at least from the academic side, the dialogue is really limited to a few senior people. Well, in fact, those who are going to create the next generation of technology are the early and mid career faculty and their collaborators in industry, and now they're collaborators in the agency that are perhaps at an early stage in their careers. We need better engagement of those of people in in that in those particular circles. This is very critical, particularly because engineers in general, don't learn about pharmaceutical manufacturing as undergrads or even as grad students. So we need to think about how do we create the proper conversation forum. The regulatory uncertainty that has been mentioned many times. I'm not going to add to that. Just to say that I agree with that. There is a lack of early funding for new manufacturing technologies. I mean, I was very, very happy to hear. Thomas Conner talking about some of the things happening in-house and some of the opportunities through funding, but from a faculty member perspective, from a faculty career perspective, federal funding, particularly in early stages of your career, consistently available, predictably available funding is critical. It's critical to your survival as an academic. So having some type of an established funding mechanism for early technology development, right? FDA is providing funding and it's greatly appreciated. But in general, the focus of the funding is further down the line for the most part. At least that's the perception from the solicitations. It would be very useful to have sort of like a technology greenhouse across the board. And I understand that NIMBO is doing something like that in the large molecule space and that's excellent. I think we need to go across the space where there are more opportunities. Then there is the problem of the value of death, right? Even when you get funding for an early demonstration, a few hundred K from a company or whatever, and you show that something works, from there to commercial, it can take easily ten years, it can take easily many millions of dollars. Again, in CISOPS, we had ten years and we had millions of dollars to make it happen, but that's not the case very, very commonly. So we need to think of mechanisms that would actually identify the things that are likely to contribute, and we need to understand how to form these partnerships where the funding is there, the workforce is there, and the opportunity for commercial scale demonstration is there. I want to emphasize that why the implementation, or even of continuous direct compression, why implementation across the industry is challenging from the perspective of a company, right? If you're coming into the space now, implementing a line is going to cost you 20 million dollars, right? A GMP line. It was going to take three years to get the line up and running from the point where you order the equipment to the point where you qualify and you're ready to start doing work. It's going to take you another year to develop your process and file it. It's going to take time to get it approved. So from the perspective of a company coming on board now, they're looking at 20 million dollars and five years of lead time before they actually had approved to make any product, right? Now, that's a very long time for the wide majority of the potential implementers. Continuous direct compression would add value in generic manufacturing, in OTC manufacturing, in supplements manufacturing. It lowers the cost, improves the quality, but it costs so large and an implementation period that long is a big problem. In addition, frankly speaking, it takes a fair amount of know-how to do this, and many companies don't have that know-how and it's hard to acquire it. So those are some of the roadblocks. So here are some proposals to helping remove some of those roadblocks. Let's go to the next and last slide. So if we want to catalyze success in advanced pharmaceutical manufacturing, if we really want to move the whole industry forward so that advanced manufacturing methods become the standard so that they do trigger faster, speed to market, improve the quality and lower cost, maybe we can do is one thing we can do is to build on the CDC's access to create momentum. So for example, if we do something to enable widespread implementation of continuous direct compression, if we really push so that it becomes available to any company that could benefit from it, we will create more confidence and we would then have an even stronger case study for people who still doubt whether or not they should go in this direction. So what do we do to enable widespread implementation? Some of the ideas we already heard and a couple more. One, I think is to create technology transfer labs that can go all the way from formulation development to supporting a filing. Yeah, third party places where companies can go and get access to the know how and the technology. This will remove the lead time and the upfront cost. So companies could actually be filing processes without having to create their online without having to spend all that money. This would catalyze activities. The companies that are engaged in contract manufacturing now have created some space that can do this, but in general, they're focused on manufacturing, not on development. If they take too many of these development engagements, then it's harder for them to actually do commercial manufacturing. So what we need is, I believe, both resources. The place that would create the formulation and the process and then transfer that to contract manufacturers that would enable introduction to market of the new product. Second idea, if we are able to do 100% quality inspection in real time, could we think of a regulatory approach for rapid approval? I mean I want to really ask the question. The technology exists where essentially you can assure the quality of every product unit exhaustively. There is no technology where you can analyze 100,000 tablets an hour. Yeah. What is the risk? There is risk, obviously, but is the risk still what we think it is? Or could we have a way where if a company really implements a quality system that exhaustively measures every quality attribute in real time? Maybe that could have some type of a default rapid approval, which would really speed things up. That actually also would facilitate creating platform formulations and platform processes. Again, if I can do 100% inspection and I can assure quality, what is the risk involved in moving from line A to a line B, where the feeders are a little different, maybe the blender is a little different or maybe the tablet press is not the same brand, but the process operates on the same principles. I'm still looking at all the quality attributes in both lines with an overwhelming statistical coverage of the things I need to know. So that would facilitate enormously how processes and products can be developed in one site and then transferred for commercial manufacturing in another site. So that the transfer of the processes would really make the business move forward. So in the process then we probably will see CDC implemented in a much larger number of applications for a much larger fraction of the product that is being produced, and it will provide a lot of momentum for other things. The second thing is we do need pathfinder programs, programs where we would be able to identify what are the manufacturing problems that require technology solutions. In the context of a dialogue between what the industry needs, what the agency needs, and what academics could do. And so in the context of a pathfinder program have a reliable source of seed funding for technology proof of concept. The next bright idea might be to do something completely different than what we're doing now, but where is the money to show that it works in principle. And have a larger pool of people participating in the conversation have more younger scientists, which could will be the next generation of people doing this. The third item, which is non trivial is and many people struggle with this is to find technology demonstration and commercialization resources find money somewhere where you will go from proof of concept to demonstration and then commercialization. There are some funding sources at the National Science Foundation, and I believe at least a focus on this, but there isn't a program focus on pharmaceuticals that will say okay we have met the criteria for proof of concept of a new technology. Now we need several million dollars to create a demonstration at scale and then to support a company to launch the access to the technology on a commercial basis. And this is one of the key limitations. Finally, I think that we need to recognize that even if the knowledge base has become broadly established for a few players, then it's actually very hard to access that knowledge for the rest of the community. And there are now hundreds of papers on continuous manufacturing but would you really learn how to do it by reading all those papers, or do you need access to some of the pieces of the puzzle that maybe reside with the people who did the development right like things like for example, a reservoir of established knowledge where we dynamically indicate what is known what we know works how to do things. Material property databases, things that enable digital design databases of equipment performance technology standards so that people can quickly come to an understanding of how to evaluate the process in a way that is satisfactory to the agency and useful to the around implementation modeling tools, process control methods and I could go on and on. And I have been known to go on and on on these things but my point is, if we really want to have broad acceptance of advanced manufacturing. I think we have to think across the technology implementation lifecycle what does it take to get it from concept to everybody in the industry being able to implement it with a reasonable amount of resources, and in a reasonable amount of time. And that's the last thing I was going to say I want to thank FDA for the vision, the support, the persistence and I want to praise. I am very impressed with what I heard about the house program. I hope that we can continue to work together for many years to come. Thank you very much. So thank you so much Dr was always a pleasure to listen to your talks. And so, let's move on to the next speakers. Um, so now we're going to have a deal in Sanders Schmittler and Stephen Colver talking. Dr. Julian Sanders Schmittler is a professor of population health sciences and medicine at Duke University and deputy director at the Duke Margolis Center for Health Policy. She served as the director of Duke's evidence based practice center from 2009 through 2020. Dr. Sanders Schmittler received her PhD in medical informatics from Stanford and was an assistant professor on medicine at Stanford Center for primary care and outcomes research from 1990 from 1998 until the fall of 2003. When she joined the faculty at Duke University. In addition to her leadership role within the Duke Margolis Center, she's a core faculty within the Duke clinical research Institute. She's currently co-sharing SMBM COVID decision modeling committee. Then we're going to have from the same from the same group we're going to have Stephen Colver. Stephen is a research associate at the Duke Margolis Center for Health Policy where he's focused on drug supply chain resilience. Stephen is also the co-founder and executive director of RISCS incorporated in nonprofit organization with the mission of preventing drugs shortages. Prior to co-founding this organization in 2010-19, Stephen held roles of increasing responsibility in business analytics, marketing, portfolio management, finance and supply chain advisor on health sphere. He worked at the Rocky Mount North Carolina manufacturing side and most recently was director of business analytics team leader advisor injectables headquarters in Lake Forest Illinois. So with that I would like to welcome you guys. Thank you very much. Okay, so next slide. So I want to just give you a little bit of background on the Duke Margolis Center and the work that we're doing relevant to this and then as Sally was mentioning going to have Stephen dive into some of our latest work related to this, the innovations. And so the mission of the center is to improve health and health equity and the value of health care through practical and innovative and evidence based policy solutions and really doing this through bringing together an interdisciplinary group of faculty and research team members and really trying to pull from all the different disciplines. Next slide. So some of the areas of focus for the center is on health care transformation where we really try to transform health care so it's more accessible, affordable, equitable and capable of delivering high value care. We then have a work stream related to biomedical innovation and so here we're really trying to drive biomedical innovation to change and innovate how drugs and devices and medical products are developed and tested and regulated and distributed. And then finally, having portfolios related to the to global health and then also educating our future generation of health care leaders. Next slide. But then specifically to biomedical innovation that we'll be talking about today is really trying to think about how can we improve this and what are the regulatory and policy solutions that could make this happen. So we are looking within the center on how we can be enhancing the pipeline and improving how you know drugs and devices and medical products are are are entering and are affordable to the patients who need them. So how can we lower development costs, finding ways to modernize the trial so that we're more efficient advancing the FDA regulatory science and making sure that we're improving the data and the end points and the methods of the different regulatory processes, ensuring value, looking to reform payment to support the development and effective use of these new therapies, making sure we're looking to improve market incentives what are some models that leverage the public and private funding to allow critical areas of need of research development, and then also looking at real world data what are the best ways to use information about how medical products perform in the real world to make sure that we're providing feedback into product development. So these are a lot of the different areas that we're working on and I'm now going to turn it over to Steven so you could tell you a little bit about the work that we're doing relevant today's talk and and some of the solutions that we're suggesting. Steven. Thank you very much Jillian and can we go to the next slide please. And as Jillian mentioned, I'm Steven Kabul also with the Duke Margolis Center and our biomedical innovation work at the center includes looking at supply chain innovation and manufacturing We actually released a white paper earlier this year in July on supporting resilient drug supply chains as a follow on to the White House executive order 100 day review report on a similar topic. And I'd like to thank my co authors, Thomas Rhodes, Adam Kretch and Mark McClellan for all their great contributions to the paper, as well as Marta was inska who was a early collaborator, and also a huge thanks to nasim for hosting this event over the last couple days. I've learned a lot and I'm honored to have the opportunity to engage with all of you. So, through that white paper that I mentioned, we define pharmaceutical supply chain resilience as meaning that a supply chain where patients have access to safe and effective drugs in the quantities that are needed and when the drugs are needed. Of course, producing quality safe and effective drugs is critical and necessary, but just doing that is not enough what we also need to ensure that drugs are produced at the scale that they're needed to and that they're distributed to patients at the time that they're needed and that that can be done consistently over time. In the past, a few factors have contributed to us falling short of that which you can see on the on the slide here we identified four main factors that have contributed to shortages in the past. The first being market forces. So in the US, there tends to be two extremes with pricing where you have high price branded products that tend to be more expensive than other countries but then on the other end of the spectrum you also have low priced generic products that tend to be less expensive than other countries. And on the low price generic product side of things, margins tend to be so small for manufacturers that they sometimes have difficulty in investing in the level of resilience that's needed. Secondly geographic concentration contributes to vulnerabilities and then in natural disasters international trade disputes, other things like that. Third quality oversight challenges occur frequently and issue quality issues arise frequently. Lastly, a lack of transparency in supply chains there's a lack of systems to communicate to regulators that the relative supply chain resilience of different products so that there's no relative contract vulnerabilities, but also for buyers and purchasers of pharmaceuticals to be able to observe resilience and reward manufacturers who have strong supply chain does incentivize factors to move in the right direction and invest in their supply chains and redundancy and other factors that contribute to strong supply chains. Next slide please. I recommend three main policy responses that can help mitigate some of those factors that I mentioned on the previous slide so firstly, financial incentives can be considered through things like targeted subsidies tax incentives for promoting private sector contracts that are contingent on supply chain resilience and promoting supply chain resilience, and also looking at innovative payment methodologies that can promote supply chain resilience. Secondly, implementing new technologies, especially in manufacturing, I'll talk to that here in a second since that's our main focus today and yesterday. But lastly, our last recommended policy response is promoting more transparency. The cares act took some steps in a positive direction for allowing the government to collect more comprehensive data to assess supply chain resilience. This sector also needs more information to be able to make better decisions better buying decisions better contracting decisions and being able to differentiate the relative strength of supply chains and quality metrics from one manufacturer to the next and one product to the next. Okay, next slide please. Now we'll go into the implementing manufacturing manufacturing technologies piece in a little bit more detail. There are some regulatory and policy levers that that could be considered to spur adoption of of new innovative technologies and all these ideas that I'll go through here are potentially applicable to certain targeted areas and may or may not need congressional action in order to be implemented. But from a financial incentive perspective grants to develop centers of excellence is a great is a great step. There was a reference earlier to a bill that was recently passed in the house on national centers of excellence and advanced and continuous pharmaceutical manufacturing. It's a great example, and there are potentially other programs that could be considered in a similar vein. Next, the accelerator reviews and filing fee waivers could be considered for products with with innovative technology or even something like a priority review voucher that's been used to incentivize uptake of products that are used to treat rare disease for example. From a regulatory perspective, there are some approaches that have been used previously that we could potentially learn from and consider utilizing for new manufacturing technologies like for example, setting a future date for when older technology may no longer be acceptable because this was used for track and trace for example and the drug supply chain security act where a future date was set where manufacturers if they're not complying with track and trace that will no longer be acceptable anymore. So that could be considered. Secondly, we could consider setting a grandfathered approval status for for older technology this was used. Many years ago, there were products, actually there are still some products on the market that are still grandfathered but many years ago when there were lots of products that had not gone through the modern FDA approval process. They were given a grandfathered status and manufacturers were allowed to continue marketing those products, but had to implement a plan to move to new technology. If a competitor comes to market using the new technology and can supply the whole market then that approval for the original manufacturer could potentially be be removed and the, the market could be shifted to the new competitors that's something that could be considered as well. Of course collaborating internationally is important, and including technology types in the FDA quality management maturity models and other big incentive that could that could incentivize manufacturers to participate, potentially to get a high rating in the quality management maturity model you need to use a certain level of, of new modern technology. That's something else that could be considered as well. Okay, next slide and this is the last slide. In terms of next steps at Duke Margolis we're going to be conducting further research on these policy levers that were mentioned. If there are any other ideas we're happy to conduct research on other ideas as well. We're trying to engage in with manufacturers and other stakeholders to identify specific barriers that that could be considered and and solutions could be, could be, could be put together around. And then, lastly, and this last couple days has been great and this last point is identifying other technologies, other than continuous manufacturing that are most deserving of potential future pilot programs we've been focused on continuous manufacturing, but also interested in promoting other technologies that can be very impactful as well. So thank you very much again for the time. I appreciate the opportunity and I really enjoyed listening to everyone's presentations and looking forward to a discussion here coming up. Thank you. Thank you so much Stephen and thank you so much dearly and it was a great great presentation. So we have been finalized with the small talks are the short talks that we wanted to present and we're going to be doing the community discussion portion. So for this community discussion. I want the audience to raise their hands in zoom. If you would like to speak up and, and then I can call you and then if you turn on your camera we can spot like you and then you can enter into the discussion. So, I'll start a little bit on the questions and I also want to emphasize, because we took a little bit longer with the with the different presentations we're going to break at 11 instead of at 1055 previously. So I have a very question just to ignite a little bit like passion from folks in the audience and from the panel to I really like you know what Dr. Lee mentioned about the extension, an incentive could be an extension of a pattern perhaps for a particular product that it's made with more innovative technology. So, a question about about that, it will be as well. What kind of metric do you do you think if you think of any or the panel, we can utilize to to ensure that we know that there's a benefit to the society right like if we're going to be extending a patent to a company who is investing in their own product and their own line. What kind of metrics can we utilize to ensure that you know we are extending this but this innovation it's supposed to do something for the greater society like you know we were talking about supply chain assurance or we were talking about process capability cost whatever so I'll just leave that there for you guys. Well, maybe I'll quickly react to that by starting and saying, um, the obvious thing you might think about is cost but I think we've already want, I think this community can acknowledge that cost, cost of goods is probably not related to the, to the cost that we have so you know one possibility is to think about environmental sustainability impacts benefits from intensified processing in that context, for example, but it would seem to me my point would just be that cost isn't is not an obvious one to me but there may be others. So, I think it would be very important to identify clearly what the goals are. I know that we really have done that in the sense that there is several conversations going on, including for example enabling reshoring of manufacturing, promoting domestic manufacturing at competitive cost. I'm not just talking about the cost of the finished product I'm talking about the economic sustainability of the activity so that you know it's possible for domestic manufacturers to produce in the US so that we help mitigate the supply chain issues, I mean there is no conversation about that, and there was that report but has the FDA taken a clear position of incorporating that as a goal for advanced manufacturing or not I don't see if the if that has happened I haven't seen that connection yet. So in the context of what is it that we want advanced manufacturing to accomplish, other than some generic, you know, improving quality by how much. So, what is it exactly that we would like to do what's the desired state. Five years from now and how would advance manufacturing here. And the report is a great first step in that direction, but we don't have a strategic plan, right, an action plan so that would be my, my sense of what we need to do, create a plan like that. I would also like to adding to that, not provoking question. So, I'd like to chime in here and just say that I do think a lot has happened in a short period of time. And one big thing that came out over the summer was the 100 day supply chain report from the White House. Although that might not be at the level of, of what Fernanda would call roadmap. I do think it gives a lot of recommendations about how we could get from where we are now to where we go in the future. And, you know, while we're on the subject I would point out that there was a recent publication from someone who we funded at the University of Maryland, Dr Cliff Rossi, and he did some financial risk modeling related to implementing continuous manufacturing domestically versus other types of manufacturing around the world. And what he actually showed in his models is that you come out ahead, manufacturing continuously in the United States versus the world. And that's even undercurrent tax rates I know we talked a little bit about tax and whatnot, but even undercurrent tax rates continuous manufacturing in the US came out ahead of manufacturing traditionally abroad. And I do think there's a lot of things kind of happening that are pushing us in that direction. I agree, I didn't, I didn't mean to sound critical quite the opposite. I meant to say, you know, I think that we see ourselves with a big opportunity where we can really find what is it that we need to achieve I think that we gave us an awareness of a situation that was not really in the public perception before COVID of the need to even from a national security perspective make sure that we are making enough of everything to take care of our population in the event of a situation and there are many situations that could emerge. I think that if you know we focus also on addressing for example how easy it is for FDA to inspect sites and to enforce quality standards when drugs are manufactured domestically versus in other places. So I think we've accomplished some very important things. And I think advanced manufacturing could help a lot. I like to move to the next step where we have a clearly identified, you know, set of goals and an actionable plan so that we all have a context in which to spend our efforts, so that we know how to help. Yeah. Yes. Yes, please. Sorry about that just just to add on I think bringing drug purchasers into the equation is also important because that can bring that can really align incentives for manufacturers to to implement the technologies that are needed so the case needs to be made to make sure why using these technologies is important and will benefit them. I think the biggest way to do that is through supply assurance, especially for products that have a high risk of shortage. If you can demonstrate that using these advanced technologies reduces risk of shortage, and then transparently demonstrate to the purchasers when you're using those technologies, then they can incentivize the use of those and bring manufacturers along quicker. Thank you so much. Thank you so much. So I just want to point out that Mr deaf baker has his hand raised so if deaf I don't know if you feel like turning on your camera there you go. Please. So I hope this is in bounds that just to join the conversation. As we talk about different incentives and things. A stumbling block that we come up against time and again is is the definition of advanced manufacturing in terms of sort of a bright line rule, as opposed to a balancing rule. I think we'll be careful of unintended consequences. Yeah, with tax incentives. And that and protections things like this associated with advanced manufacturing, because it lends itself to making lists. Yeah, let's go through the plant and put a yellow sticky on every piece of equipment that is advanced manufacturing. And time and again, we come up that advanced manufacturing is not a list of nouns, it's about how you do something. You can have 20 year old equipment that you use in a constructive innovative progressive way. You can also buy brand new stuff that you do batch binary pass fail offline release. And, and I think that this is a hurdle and I don't really even have a good suggestion on how to address it. I think about this when we say oh we'll give a tax incentive for this or benefit for advanced manufacturing. How then do we codify how then do we go to the IRS how then do we go to the agency and provide these bright line rules of what is or isn't many advanced manufacturing, when in fact, it's how we do something, as opposed to what we use to do it. And that in a buck will get you four quarters but as we go through and think about all these different options, and they're great ideas, we have to also think about the implementation. And I think these things lend themselves to sort of bright line rules as opposed to balancing rules. And that's hard. Thanks for your patience. Thank you so much I was a great comment anybody wants to add to that or just to comment. Just a point I think Kelvin brought that up earlier right the definition is it is hard to do and certainly found ourselves. And that's why I think in the word technology program we tried to operation that program we didn't really define it. But you know we had two characteristics you want to have something that we had limited experience with so it's easy for us to find and have the on the onus of the sponsor, how it's going to prove quality right and they can make an argument. That valuable, you know we can accept in the program and provide the sport and work together. I had a thought actually. We are almost talking about implementing advanced manufacturing as if that is the goal by itself. But one could argue that the goal really is to improve productivity, for example, right. If we focus on that one way I think in which we can move the whole field forward is if FDA really were to ramp up the quality requirements if you were to require stricter quality demonstrated much more thoroughly across the entire quote unquote batch. The only reason of a way to achieve that for most products would be to implement some type of effective exhaustive online analysis of quality attributes coupled with, you know, real time close look control. And whether you're doing it in a continuous or in a batch or whatever if you're achieving the higher quality standard and you're using tools like modeling sensing process control and automation. You are achieving the goal and that to me fits under the definition of more advanced manufacturing. I think that that would move everybody in that direction. And that as well. Right. And then the problem of the yellow stickers disappears because, you know, it's a combination of tools that achieves the goal of higher quality. Yeah, and let the market drive all surprises, I think. Thank you so much for that. So just we have a couple of other questions in queue so we'll like to extend opportunity to other folks as well. And that was a great discussion. So I'm going to go to slide out now. There was a question that was posed yesterday, but Narendra bomb, and who got many likes. So we're going to go with that question. And the question is, can we create a regulatory incentive for key manufacturing technologies that will advance the whole field, similar to breakthrough stars. So that's a question that I know that Narendra, it's here. So if you if you want to turn on your camera, it's really up to you. But I just wanted to read that question that was a place yesterday and got a lot of lights in our slide out. So if I spoke too fast, I can read it again, because I know that I think very fast. There we go again. So this question was, can we create a regulatory incentive for key manufacturing technologies that will advance the whole field, similar to breakthrough status. I think thanks, Sally Narendra here, can you hear me. Yeah, so I was thinking that the breakthrough status designation actually allowed a lot of things to happen from and from a sponsor perspective innovative perspective it gives us real time access to the regulators, which is often the biggest hurdle for us to actually plan and get something established. So I think that's one aspect of breakthrough status like designation could provide to the innovators from a benefit perspective. So is there is there a breakthrough status for a manufacturing technology that gives us this open door access, not just with the ETT, which is always there but with actually the reviewers of files, the actual inspectors who are going to come on site so industry wide access. Thank you. So let me, let me kind of jump in here. You know one thing I do want to clarify is that the key value of the ETT is that the reviewers are part of that program. So it's not a separate entity these are people who are who are actively involved in those technologies. I believe my cops are mentioned this yesterday we had a quality pharmaceutical quality symposium earlier this week, and this topic came up there as well and someone asked me about regulatory incentives for advanced manufacturing. And you know one thing that I wanted to point out here that I that I also pointed out there is that in the emerging technology program if you look at the approved applications. In all cases they've been approved ahead of their user fee goal date, the typical user fee goal date. Right and a big thing that we hear is people are right about the risk of implementing these things delaying the approval of their product. If you actually look at the data though it's the opposite. In many cases these things have been approved in advance of when something typically might be approved. And so I just want to relate that a bit to this idea of breakthrough status, a number of the advanced technologies we've seen have been used to manufacture breakthrough products. Right. And so that alone brings an accelerated timeline that we've been able to meet via the emerging technology program. And then the other thing I just want to point out very quickly is that often what you see in new drugs is that the rate limiting step is the clinical. Right, it's not necessarily the CMC that keeps things from from being approved. Sorry. So I want to make sure that we we keep our eyes on the factors that kind of matter that drive us to the place that we want to be. I think that place needs to be focused on improving things for the patient. Right. And so Fernando had had mentioned the idea of having higher quality standards and that sort of raises the bar and you need advanced manufacturing. And I think it's important to keep in mind that no matter what you do it needs to result in a safe effective product for the patient. If that's a an existing technology, so be it. If that's an advanced technology, perhaps there are some advantages that could be realized from from doing that. And I always keep in mind there's this hierarchy of quality, right so the product quality, this process quality, and then there's quality management. And I think what we're talking about here a lot is somewhere between the process quality and quality management step. And that's what makes people confident that the things that they manufacture can be released every single one without any disruption and supply. And so that's kind of my take on this at least. Any other comments with regards to that. If not, let's move. We have another question from Tim team. If you can show your, your face in the camera. If you want, if not, then we can find another question in a slider. There you go team is coming. Thank you Tim. Hey, Sally, you know I'm trying to remember my question on slide I was going for something else. Oh this was about the incentive so we've been talking about that. And I actually probably would upvote a couple of the other comments in there I think Rob Danard had one or two that were related to this as well and you know, it's about the dynamic within the companies, you know, I think we're we're a lot of this resides and so if we can reflect on and try to find ways to change that dynamic to one in which there's a poll coming from, from people within the company, rather than the bottoms up push of look at this technology. At this point, you know, it's not going to slow you down don't worry to what can you bring forward in the advanced technology space as a part of this product that will be dramatically different than the history has been, you know, because in reality, you know the people that run the projects typically are focused on the clinical label and the timeline, and you know they are very worried about all of those risks alone as they as they will impact the business, and those management folks are concerned about anything that will add to that risk or timeline. And so even as Adam said if the data are there. A lot of it is because there's been a lot of reticence about still, you know what what you end up seeing there because of those concerns and I think flipping that if they can find ways to drive those incentives and the other direction, you know and having people calling down into the into the manufacturing and process teams and saying, What can you bring us here because we want these advantages that would would would be, you know it's kind of a soft thing in a way, but it could actually change the dynamic. And maybe if I just build a little bit on that and tie it to some of Adam's comments I mean I think it's, I think the, if there hasn't, I think if the data shows there hasn't been significant delays associated with new technology adoption. I think that's key and important information to share broadly. But the flip side of that coin is, there may be other approaches and technologies that companies have decided not to pursue and put forward because of because of what they perceive as potential delays. And, and I think those decisions my senses are are made early in development so yes clinical is going to be the slow step but companies have to think about what approaches are going to take to manufacturing. And that will come relatively, I think on the earlier side of things. And so, as Tim was reflecting, if those conversations today are, you know, what is our risk of whether we get this product to market or not and how fast can we do that with current technology. If there's now a conversation that has to happen, well, we can do it with current technology and get what we know we're going to get. But if we have a better way to do this, that will yield other benefits, and we'll also take some additional benefits to benefit. Maybe it's worth pausing for a moment to think about whether we take an advanced manufacturing approach versus a call it a traditional one. And I say that recognizing just comments about whether advanced manufacturing is a technology or perhaps a philosophy. And I think that's a really important consideration as well. I just want to point out it's 1101 and we have a break now. I don't know if any, I don't know if the academies want us to take one more comment or if we should break and then whenever we come back to session five a path forward we're going to have another community discussion. So we can all take a break now and perhaps save some of the thoughts and questions for the next session which is going to be again another community discussion. What do you recommend Linda. It looks like maybe a break would be good just to get people up and get the blood flowing. But the next session is really open floor. And I think we have a lot of comments coming in from Slido that we would probably bring up in the next session. I don't know if the speakers are going to be. I know you all have very busy schedules they would be great if you all could also participate as audience members and we just get the floor open and bringing people on stage to discuss their ideas. So I think a break would be good and then moving on a session five to continue the conversation. Excellent so so we're going to take a break now and then we'll come back at 1110. Next session. Right. Excellent. Alrighty well thank you so much see you guys soon. Very good. So, I appreciate those of you that are persevering and staying with us. Just to recap what the design has been of this workshop we started out with session one. And really we're focusing on revisiting the technology inventory that the committee had put together and and identified as being those technologies that are the FDA can expect to see within the 10 year horizon. And then in session, we looked at, you know, some of the, the challenges that that innovation encounters, and we saw some very interesting response from the FDA, telling us exactly how they've taken on some of the committee mid and some of them they chose not to pursue. We then went on with a gap analysis so the idea here was again to revisit some of the issues that the committee had identified and the solution that we proposed and and identify things that we had missed. The session we just experienced together was to now point to those gaps and identify some ways we could address them and we certainly had some very exciting presentations given by a number of the participants that really outlined a whole set of suggestions and ideas. And yes, the by design the purpose of this session is to say okay, we looked at this whole path, we have a whole selection of possible avenues to pursue. So what really should we do, you know what should the community do. And I think that's a really important part because it is relatively easy to say well, you know we dump it all in the FDA is lap. And it is for them to worry about enabling introduction and new technologies. We really need to take ownership as a community and figure out what can we do collectively to move things forward. I think there have been a number of strategies that you know we have identified and certainly I would say the examples provided by by Kevin and Fernando of, of basically, you know, industry university government partnership that bring together segments of the community to address focused issues. And I think the notable part of, for example, nimble and seesops is that these, you know, did not majorly require FDA financial support right there are other sectors of the government NSF NIS that actually helped underwrite it. And, and I think, likewise, one doesn't need to rely entirely on government funding. It's conceivable that industry consortia could get together and move forward certain subjects. You know, issues that that were surfaced about globalization. And, and certainly we saw a number of ideas of promoting communication between the regulators accelerating the adoption of new technology by having the regulators get together and look at them jointly. So there was ideas, for example, of some kind of memorandum of understanding so when ETT addresses a new issue they bring in some of their collaborators from from Europe or Japan and do it in some sense jointly so that the company is not doing this serially. I mean, these are some of the things that some of them can point to the community some of them can point to the FDA. And I think what we want to do in this session is to really get your input on what you think are the most productive ways to move forward. Clearly we need to engage the community. We need everyone to participate to move advances in manufacturing forward. And that's the purpose of our session here. And with that little introduction I guess what I would like to encourage you now is to fire away with questions and ideas that we can post and discuss as a group. And I see you on the screen. Does this mean you want to say something. Well, it means that I'm happy to join and get and encourage others to, I certainly don't want to, you know, take take more more space than than is absolutely required because we really would love to get people to chime in here and, you know, get a conversation about what we're doing. So, you know, the more faces we can see, I think we want is free falling a discussion as possible here not, you know, depend on Slido, you know, for this next step but to try to get, get, get something moving quickly and I guess I would say, you know, I'm certainly happy to raise my hand for what I can do to help going forward and, and, you know, I would love for both mechanisms to be created for ongoing conversation. I've suggested some follow up workshops for this. And, you know, I have been in communication with people in various forums as we've been going along here, you know, and it's clear that people want to contribute and I think my view would be that we want to take advantage of both the momentum and the energy of folks throughout the ecosystem to try to advance, you know, this this mission going forward I totally agree with the, you know, many people's comments that you know this is a community and, you know, I really hope that we can find ways to not say well it's your thing it's your our thing not ours or whatever but it's all of our thing. And, you know, then for people to take action, you know, and I really liked the idea that that that we heard earlier, you know, first, even a strategic plan, you know, collectively as a community that's actionable I think is is a brilliant, you know, and really required thing if we're going to make a cohesive stab at this. So, thank you for that. I think that was Fernando's comment and really appreciate that. I also appreciated Kevin's focus on the fact that it's all about patience, because certainly when you get to be my age you realize that, you know, you have your imminent to be a patient so you have some some enlightened self interest to pursue there you know and I know Tim is a young fellow and our young ladies here they're they're way past worrying about these things but but I certainly do so. Kelly or Sally did you want to offer some comments. Kelly, you can start first. Okay. So one of the things that strikes me is clearly there's a lot of effort going on inside the FDA to promote innovation. And clearly there's a lot of effort external to the FDA to promote innovation. And yet, it seems that there's not great alignment, either in the timing the focus for, you know, it's almost like parallel efforts that intersect only with more heroic interactions right across the ecosystem because connections only between regulators or regulators and, you know, government or other other government. It really is the community in the ecosystem, you know, working together that needs to happen, not just sort of bilateral right, even though everyone has their individual spheres of influence that work. I know that the committee as we thought about writing report and, you know, considered the larger community effort. The alignment of all of these efforts is is really in my mind the sticking point, you know, the starting and stopping of government funding can be a problem, right that is not necessarily controlled within any agency's control since that one has an appropriations component to it. And then, you know, changes in leadership of different countries of companies and the cultures, you know, risk aversion and all of that. So it is a complicated problem with a lot of moving parts. The point is, I guess, is that I believe that there are a lot of existing assets, but it is the incentives and the alignment of the incentives, where I would recommend we focus efforts. I mean, I would like to add a little bit to that I think that just like Kelly I would like to start by acknowledging all the efforts that I have seen at the FDA. So I think that, you know, like we started again with a pate initiative that's something that needs to be acknowledged that it was a very strong document it was very change, like a game changer. I think that it's something that started at a point that you know when you are ahead of everybody else that you're way ahead of the future like you're almost there so I think that the vision is there I think that the support is there. And it's now, it's going to be like companies when we hear about these things and this is my perspective, like this is not the National Academies perspective this is mine as working in the industry. I think that when companies hear a new term, there's a new initiative like everybody johns jumps to it everybody wants to use it just to ensure that their management sees that they're trying to innovate and stay ahead to the curve. But sometimes, I think that the reasons are not very clear of why we're doing it and I think that the business case is not very strong and I think that this is something that we're not brought in the chat to. And I think that if we do an analysis and we stop, and we start understanding that not all of our processes are monolithic that we start understanding that we don't, I mean their products that we just made once every two years, and there's one for their products that we make 25 batches a year or more or 100 batches a year. So the needs for advanced technologies is really going to depend on the product. So I think that it might be might be and this is not something that should be on the shoulders of the FDA and that they should be in our shoulders as an industry, perhaps leveraging like limbo or leveraging the International Academies of engineer automation like this other avenues that we have is to start really thinking about it from a business perspective we love technology we love to start talking about artificial intelligence and data analytics and all the sexy things. But are we stopping and thinking about the business and about the patient and what we're doing for our society and why we need pharmaceutical industry it's not like make up industry it's not like a cell phone industry. Think about it about like we are providing medicines for our population it's almost like a hospital we're almost like, you know you think about what we are doing right now. And, and we, we need to start thinking what are we providing to our society, or what impact we're having towards society. So I think that once we start seeing not only about the technology but the business processes the impact that we're having why there's a need to change, right because it's about change at the end of the day, then perhaps, you know, we're going to start finding finding common ground but if we're just still talking about you know the algorithm, and we talk about like the, the Raman and the NIR and then we still kind of like fall into that conversation I don't think that we're going to be able to make like like a strong move in our industry. Those are my two cents. I'm going to jump in, because I would like to respond to both team and Kelly. So, a couple comments, number one, there is a potential major opportunity coming up which is this bill for the centers of excellence, which has passed the house three times, which would place $100 million at FDA for centers of excellence in industry, right. I wanted to suggest, I think since it passed the house three times we can hope that eventually will become a law and the resources will become available. If you could do something in the meantime, which would be very, very useful I think which is something that needs to us and that the EDA has recently done which is basically to fund a small size planning grants, universities that intend to become the centers of excellence to develop a roadmap for implementation of advanced manufacturing that those grants can be you know in the 200k to 500k each but they provide a process by which universities convey industry into a dialogue to focus on goals and how to get there. I think that in terms of a strategic plan right, the strategic plan, you know again, could be many things but it would be very interesting to have a clear statement of goals what we want to accomplish right, specifically, and then focus on pathways to get the leverage everybody's contributions and potential, you know, and give an opportunity for all the different voices to chime in as to what are aspects that I might not know about and you know maybe he knows about or somebody else and we can then engage in the dialogue but I think it needs to be goals, you know outcomes driven to Rex might remember that we use that all the time in CSOP. I think outcomes driven is important what are the outcomes we want by when do we want them, which steps will get us there. And I want to mention, you know, CSOP some nimble and things like that even camp happened because there were, you know, faculty that got together with a couple companies and push. It wasn't in response to a grand vision that was, you know, trying to address issues of supply chain or issues of quality or issues of cost. If we had had that grand vision, if we had had those goals clear, I think we will have done many more things. It was all driven by happenstance to some extent, right. So, you know, luck is not a plan right so why don't we create a plan. That's an excellent idea but a follow up suggestion was, you know, within which framework do you envision launching these exercises. Well, I think there are multiple opportunities right so FDA has funding available and FDA could make the choice, for example to say in the next solicitation we would like to award two or three planning grants for you know universities that would actually like to create these centers of excellence to begin to articulate how they would do it right and who would they work with etc that would gain us a lot of time right because otherwise we're going to have to do that anyway in the context of rushing to write those proposals for those centers of excellence if and when the bill gets funded and if the bill doesn't get funded this planning efforts might be useful in the meantime right. So how do we get to a truly portable contained, you know, inside a glow box manufacturing system, but does it take to make a GMP, but portable right. All the thinking that goes into that could be done with a relatively small amount of money is the planning, right. I think that that would be very useful. Another thing is FDA could reach out to the other federal agencies that have a vested interest in this right there is money in other places, there is the economic development administration, right now. The military have indicated that they are very interested in this right bar the DARPA their funding things that are relevant to the NSF, you know, other agencies have gone to NSF to create new ARC targeting certain needs. There's absolutely no reason why if they couldn't again approach NSF and say hey how about we invite solicitations for ARCs seeking to accomplish X, Y and Z right. All of those are long term programs and that's the message is that technology successful technology implementation takes a long time. And most companies do not have currently the philosophy that allows them to implement this long time development efforts right I mean many, many companies don't do that. So the frameworks could be based on the existing long term centers, they need a twist towards technology implementation and technology transfer, rather than fundamental research. Thank you for the really helpful comments looks like we're getting some interest here, and I just Linda and Sally speak up about how you want to run this part of the process. You have in the chat, you know, but if folks it. I think what we were thinking of is if you if you just turn your camera on, we can bring you forward and get get things going we don't have to use the hand raising necessarily if you find that it's going to be chaotic. You know we can we can dial back but we want to get the voices going. And it's exciting to see that people are looking to speak. Tim, you hit it on the nail there. This session is going to be a bit more chaotic in the sense that we really want the community to see each other to talk. Just imagine that we're in an actual room physically. And so if you feel the edge to talk to just talk. We don't really need a calling you just unmute yourself and just chime in. And we'll see how it goes. That's dangerous but let's see how it goes. Well, you know, we have a raised hand there, please go ahead. We had Jenny and who was very brave so. I think the conversation off in a slightly different direction so I don't know if Kelvin or somebody else wanted to continue what Fernando was talking about just then. I can just maybe offer two sentences and then if that's okay and then kind of doing a new direction site. I want to say that I do like the idea that we would have some kind of broader strategic vision and plan I like the idea of engaging as much of a cross-section of the community as possible. I think identifying resources is really important and if that means investing and helping the academics define that vision because academics are really good at convening. I think that's important. I think a risk there though is at least what we've seen in our part of the community is that the academic community is much is years behind. Current industry thinking and knowledge. And so I think it really we want, I would argue that whatever plan we develop as a community really needs to be led from the industry side because they're the ones with the state of the art knowledge. They're the ones with the proprietary knowledge on what's where they're going. And finding a way to have them lead the discussion I think is going to be critically important and so and of course they're resource limited as well. You know coming up with a national strategic vision for this is not in maybe the most obvious thing. So with all of the alphabet soup of agencies that are relevant. One concept to put forward is maybe this is something in the context of domestic supply chains and resiliency access to medicine. Maybe it's an OSTP led discussion about how multiple agencies can coordinate to facilitate that conversation. Thanks very much. Good point. We do need to get the industry direction setting because it is quite true the academics like to pursue our favorite topics, not necessarily the ones that have the most impact. But the trick is how to how to convene that. That's really the challenge. I wonder just following up on that just very briefly if there's a way that we can leverage the data that is coming in from the request to ETP to identify some topic areas that are of broad interest where there can be a industry regulatory academic discussion one that comes to mind is you know rapid micro testing or machine learning. Those are topics that I heard multiple times during these two days. And while it's great that ETP exists for FDA to engage bilaterally with companies on these topics. It seems and I think Fernando mentioned this in his talk, like a little bit of a missed opportunity to not be able to share, you know, the broader feedback with the entire industry on those topics that everybody's interested in. Just a thought. I don't want to, I don't want to comment on the project. You go first. No, I don't want to comment on this. I think we agree. I think one of the ETP or two porno is to enhance communication. But I do want to say that these informations out there as well in the ETP website. We actually list the type of a technology we have engaged. But I do want to make sure that some of these information are somewhat like we can only share like at the high level in our opinion in a certain way but like those are broad topic what we have been looking at. It's already, it's already in some of it's already in the ETP website so I think I encourage you guys to check it and then we will also update the website regularly. Janine, would you, we need to give you the floor here. Just to that point as well is that I'm in an incredibly privileged position because now after 18 years as a regulator at MHRA I'm now writing for IPQ and international pharmaceutical quality and so I get to go to lots of conferences. And I was like listening to FDA and industry conferences sharing the dialogue on new technologies is quite phenomenal. And other regulators too. And, and so I guess I get the image that there is a lot of communication going on and so it's quite surprising to hear that, you know, the messages aren't always getting out. And, and I think that's a huge thing that we could potentially help with because we, that's what we like to do is to enable the dialogue and share the ideas that are discussed at conferences, but also maybe engage more academia at conferences and at least enable them to go to these conferences run by membership organization that bring regulators and industry together to share ideas and, and certainly going to so many conferences. And the thing that we hear over and over again is about new technologies and the nervousness of bringing in the regulators, the worry about sharing things, in case you say the wrong thing, and that sends the regulators off on a different path but there's a point that's been made really, really well by Fernando and Kelvin and others about the global issue, because from my understanding and what I hear so often is that making changes with FDA with MHRI with with some of the other regulators is really great. There's lots of good opportunities with the ETT the innovation offices and things like that but, but when it comes to other regions, the, the challenges there of trying to make changes is, as others have already highlighted in the report showed is, is a huge challenge and most companies are global and, and the challenges that they have to go through the, the length of variations. It's, it's a big blocker. So, I'd like to come back to our conversation and see what else can be done about it I did suggest that possibly with all the fantastic work that FDA are doing that. There's a training as well that's going to be going on then. Is there any possibility of sharing that with all the digital tools that we've got over the last 18 months or so. Is there any chance of being able to bring in the other global regulators for more in a discussion in the end using those tools. Thank you Janine I think we should switch to John he's been patiently in the queue. John, would you like to hold forth. Yeah, sure. Okay, two things that I wanted to say one is since we've been talking about regulatory agencies. So, it was an interesting comment that you know a lot of the things that have come through the ETT have been approved on time. I'm not sure and I don't know if we have data on this whether the problem with new technologies is that the FDA says no to them, or people just don't have the confidence to even approach the FDA. I think there's there's there's a huge number of technologies that never even get to that point. And so one specific thing I think that we could do would be to think about ways to increase people's confidence in approaching the FDA and not just saying that now they'll don't they'll never approve that. So that's one thing. And then the other thing is that we can have a manufacturing strategy, but I'm thinking there are roadmaps that exist. And I think what we really need are specific projects that specific companies want to work together with specific consortia to push over the finish line, because that's how you really get things moving. Very good point. Thank you, Rob. I believe you are in the queue next. Great, thanks. Yeah, it's great, great conversation. Really excited to hear all the conversations going on. One thing that I kind of think about in all of this and, you know, I kind of like what Sally was talking about sort of like, you know, you know, in the early 2000s when we had 21st century GMPs, PAT stuff, right? I think there's a lot of lessons that we can kind of learn from that. And I think one of the lessons is is that, and I've heard in this conversation probably the word change a thousand times right and so I think, you know, one of the things that you have to change is that you have to really manage a change as a change, right? And there's a lot, there's capabilities on how you manage change, right? And I don't see a lot of those necessarily being applied to this big problem, right? So we're trying to move a complex dynamic system of this whole thing, right? We're trying to modernize the industry, right? And there's incentives, there's investment, there's technology, there's all these things. But we haven't really kind of put it all together like if I was, you know, to hire a consulting group to come in and manage this as a change, right? I don't necessarily see that we're taking sort of that social science approach to this. And for me, and having done this in different organizations, the more that you can kind of apply that the better things start to work. And we've talked about a lot of key concepts like what is the future state? Where are we now? The steps, like, you know, we're talking about a strategic plan. There's a lot of different stakeholders. Where are they on this journey, right? And there's sort of a whole management process that has to go on. And so for me, like one of the things I think about is actually taking a step back and saying, where are we? Where are we trying to go? And I think, you know, some of the folks from Duke were kind of talking about sort of like from a healthcare system. But I think the technology, like we do want to move the technology forward, but we have to understand why are we doing it and who's benefiting and then the change process around that. So I'll kind of stop there, but I see there's a lot of opportunities there and there are a lot of barriers, but there's also a lot of things that are on our side, a lot of key enablers too. There's a lot of discussion going on, but like if I were to think about managing this change, the resources that are managing the change are very diluted. There's probably like, there's so many different, you know, bodies and, you know, sort of conferences I can go to, but it's not concerted, right? It's just, it's kind of more of a shotgun approach. So can we start to, you know, consolidate that? And, you know, one of the change philosophies that, you know, we've kind of adopted is, you know, it's, if you want to go fast, go alone. If you want to go far, go together, right? And there is a real piece of that around us going together, but it's hard to go together when together is fragmented. So just want to make those couple of comments. Excellent. Very valuable comments. Stelios, would you like to get the floor? Sure. Thank you. And it's exciting to see so many experts here and the diversity of thoughts. And I will continue along the lines that Rob said. I think what we are, while we have a great strategy and thinking, I believe what's missing here is the business case, the business case to support why advanced manufacturing makes sense. And that's why we should implement that. And I will speak mostly from my experience in industry. I spend most of my career in industry now in the regulatory agency. And one of the things that Fernando pointed out, rightly so, is that we haven't identified as industry, the cost associated with defects with the processes that we currently use, and the efforts that we put in to investigate deviations to deal with loss of product that at the end it's beyond expiry date because we keep manufacturing it in batches and then we stock it up because we don't, we want to have the flexibility to have it available there. So I think an area where industry and academia can work together and where academics can help is actually enabling industry truly assess the cost with loss product and defects. And I believe that could be a factor that will play a role in putting a business case that if we implement advanced manufacturing, it gives us flexibilities on the stock that we need to have. It gives us flexibilities to move from one product to the other and minimize the losses. I believe we may be able to push industry to toward that direction. Thank you. Thank you for that comment. Jack, you've been patient. Would you like to take the floor. Oh, sure. Yeah, maybe just to comment on john's question about sort of FDA encouraging innovation. I mean, I think I made this point when I spoke last year was it two years ago that, you know, we're governed a little bit by the least common denominator, I mean, perhaps, you know, some companies have the scale where they can have a US dedicated, you know, plant or production line and really push that into the limit of what the FDA would encourage but ultimately you need at least to serve, you know, in a first round the EU in the US. And so you're going to look at commonly what what can be done. And if you're looking at, at change right put our first goal is to get to market as soon as possible actually was in the hospital with a relative yesterday and a key drugs you need has a Padoopa data January 28. And God I wish it was just January 1 to well, you know, and there's a lot of patients like that so our first goal is to get drug to patients fast. And so you don't want to take anything that would slow that critical path down, and that starts with your early diagnosis and then every time you, you know, you can scale on the clinic but ultimately get to get to market fast and then do the innovations later potentially but that's, then you've got to manage the supply chain, many, many markets. The question that I put in was, you know, the suggestion earlier kind of bright line definitions of incentives for innovation technologies and it's just maybe a little bit cynically worried that, you know, do we have good examples of innovative approaches that you would have if I put a digital twin somewhere on my, on my line is that innovative, you know, if I put p a t somewhere I mean you can have very superficial implementations are very transformational ones. I don't have the answer but it's a little bit of a minefield. Very good. Thank you, Jack. Tom, I believe you've been trying to get back in. Would you like to take the floor. I didn't have anything to add so I don't know whether it's just because my video. No, I agree. I think it's a great discussion. I actually thrilled to be part of it and glad that we're having it but I'll let others speak. Okay. Now Sally, did you, I know your hands up and I'm not supposed to give committee members priority but you're very important. Thank you so much. Um, no, I just I just want to piggyback into what Rob Gennard said, because I think that I don't know, you know when we're talking about business case and we're talking about stakeholder analysis. Many times, you know, like we, like, again, let's go back to the p a t initiative and start talking about incentives and benefits for pharma. I think that we should pause and then think, okay, what are the different benefits that we have for stakeholders? I don't think that we have done that exercise and say, you know what, these are the benefits of some technologies, right? Because not all of the technologies are going to have the same benefits or not all the innovations are going to have the same benefits to pharma, to the business itself. These are some benefits for the society. And by the way, these are some benefits for the agency team because they have to, I don't know, I'll give you an example like we were talking about, you know, the quality metrics and that project that that program. I don't know the status of it. I think that is going to like, there's going to be a revision to it. But that is actually to benefit the agency as well, right, because now they don't have to be doing. You know, they don't have to be investing some so many resources in going and investing in companies just to check on the status of where they are at. So, I think that that's going to be important because what in my opinion, one of the reasons of why some of the technologies have failed is because we have, we have tried to put the same benefit for all of the technologies when there's not the same benefit night, like, as an example, not everything is going to be ending up in real time. So, and it should not right now that might not be the benefit the benefit is might be saving a battery might be not having so many inspections, or might be, I don't know, like any other so I think that we have to. In my opinion, like one of the things that we have been trying to be like to black and white about the adoption of technologies and it's not, it's not as simple as that. Thank you for that observation. Adam would you, you're you're in the queue and I'm not sure which comment you're responding to but please do. Let me try to respond to a couple actually. The one that I wanted to mention was this idea is saying more about the technologies and emerging technology program. And a point that Larry hit on earlier was that you know we have to adhere to confidentiality right so we rely on companies to go out and say that they're part of the program and what technologies are part of the program. And once they do that, then we can talk about them, but before that happens we can't really say anything so I think that's a great opportunity where we can kind of work together to increase the visibility of some of this stuff, and maybe de risk a bit in the eyes of the decision makers. And then the other thing that I, I did want to mention in terms of a potential path forward. And I'm not speaking as a regulator here I'm speaking as a scientist I see a lot that can be done in the pre competitive space. Right in a good example I think is this whole idea of microbial testing. Right. We shouldn't be using tests that they used in the 1800s, as we're also talking about implementing artificial intelligence right it just seems like something that's discordant. And I think the technologies are out there that's the frustrating part over the last 20 years the advances that they've made in microfluidics and cytometry and labeling those things should be able to be pulled together in my eyes to give you better microbial testing. And I know there are some efforts, I believe nimble has a project that you know that they funded in order to develop a rapid microbial testing and there and there's some other tests out there. But that's the type of thing where I see people with different types of IP, coming together in the pre competitive space to make this possible for everyone. And we didn't really need a better mouse trap to this point, which is why we still have the 1800s method in place. But as we do take this more real time approach to manufacturing. I think we are at a point where that old mouse trap doesn't work. And those are the types of things that I do believe people could come together in a pre competitive environment to work on. Very good. Thank you for that. I noticed there, Fernando, did you have a question to pose. No, that that is from about half an hour ago. Okay, sorry. Between chat and, and you know, Slido and whatever it's hard to keep track of where we are. I don't see anyone else. Was Mike was Mike trying to chime in? I thought he turned his camera on. Sorry. My cop jet had his camera on there for a while, I think. Mike will come on to wrap up the meeting. Okay, thank you. Sorry. I wanted to, to be sure we capture any comments that that may still be here. And it looks like Kelly, you have one. I do. Thanks. I'm just curious from a data perspective. The emerging technologies program has been open for groups to approach to discuss technology since it is not limited to being attached to a product. And then Dolores mentioned that, you know, that's been their wish as well, right? Support in other regulators. So I guess that my question is how often has that happened? And what has been the outcome of that? Is it a visible publication? Is it? Or has, as no one sort of accepted the challenge of bringing a, you know, an industry group bringing a technology before the ETP? Adam or Tom, can you respond to that? I can respond to that a little bit. I think, like, just to Adam's point of perspective, we do have the group come in to talk about certain tasks as more like a consortium basis, right? I mean, the, the, the problem I can see is that it's not about like, why don't we have a forum? We already have a forum for people to come in to talk with a group. The company among yourself, among the companies, they need to establish confidentiality agreement. How would they like to share, right? Would they be able, so this is also touched upon by Adam's comments, right? I think they come, like you guys, I think that need to be more collaboration within the industry to be able to share the information together because I can see the advantage is that, let's say, microbial testing, right? You guys, each company can have their own data and then put it in the, like, more like a comprehensive data set and then to show it to us. So I think this, we already see some of the examples based on our previous experience. So I just want to share, but the problem of this would like, like Adam say when, like people, certain groups are doing it, but, but they don't really tell other people. So, but for us, it's a little bit difficult sometimes because of a certain confidentiality, confidential information there. So I just stopped here. I'm sorry that that helps a clarification. Jim, Cyril, you are in the queue. Yes, yes, thank you. Yeah, I just want to say real quick that it'd be nice to get CBER just as engaged and get alignment between CBER CBER and the rest of us and the hundred other countries as well. Yes, I think in one of the earlier FDA presentations, there was an indication that there is communication between the two groups and sharing of ETT-like activities. So that is, that is already happening. Well, I think if we have no further, sorry. We have one more raised hand from Rob. I blew your transition. Just one other quick comment about sort of the change in the, in the, in sort of the, you know, the value proposition, the business case, whatever you want to call it. I think there's actually some lessons that we can think about from a lot of movements and a lot of other places. And, you know, if you're familiar with sort of Daniel Kahneman's work on change and, and, and the work of like thinking about it from, you know, an economics perspective. You know, the thing he talks about is that the, you know, for a movement to happen and a change to happen from the current state to the compelling destination. And I think, I think the articulation of the compelling destination is really important because it has to become compelling right. And if you think about all the stakeholders and that really thinking about how do they fit into that compelling destination and then how do we sort of get them there right. And the, it's, it's well studied that it's a two for people to want to move to that compelling destination that has to be two to three times better than where they are now. So, so really starting to take a step back and thinking about that and how, how is this two to three times better for me advanced manufacturing or, you know, however we want to sort of think about modernizing, you know, sort of the means of production of medicine right for me, I think there's there's a discussion there right painting that compelling destination and then understanding all the stakeholders and saying, Where are, where are they now and how are we going to get them there. And, and, and there's a there's sort of the driving force but then there's the kinetics right which is kind of to the point I made about the strategic plan so I just want to make that comment because I don't think it's just about dollars and quality, I think is a lot of measures that matter right. It's sustainability, it's the social purpose it's all of those things. And those, those drivers are going to be different depending on who you talk to. And if you have the holistic picture, then you can start to sort of like have the right conversation at the right time so I just want to make that comment and it's just something I've kind of observed kind of, you know, coming from the industrial industry and kind of coming into, you know, pharmaceuticals many years ago but can start to see how different drivers affect how what you're trying to do, especially in the innovation space so just wanted to make that quick comment. Thank you Rob. John, you're going to be officially the last comment so please go ahead. Okay, what an honor, thank you. Rob, you have me be thinking talking about you know if you need to have the next step step be two to three times better. Do we want incremental change, or do we want transformative change, I think sometimes incremental change is easier if we make this just a little bit better, you know there's there's less risk. To your point, you know, maybe we should think about the transformative change and the transformative change usually means changing a lot of things at the same time to get to that next vision so you know, I'll just just leave us with that and maybe that's a longer discussion to be had, but if we had that great grandiose vision was there's a lot of risk there too and how do we manage that. Very definitely. Thank you very much for for that comment it's actually a very nice comment with which to end because for sure. This community is not just happy with incremental change. We really want more substantive change. I get the official 12 o'clock time and so the appropriate speaker now is Mike Capcha who's the effectively the sponsor for this workshop, and Mike you get the last word. I get the final word. Thanks Rex. I did want to point out because I did have a couple of comments I wanted to make in terms of the questions and the comments that came during this last panel discussion. First of all, I do want to point out that both Cedar and CBER as you correctly highlighted Rex are indeed working together around advanced technology or advanced manufacturing, you know, whichever way you want to define it. We've put together what we call the Center for Advancement of Manufacturing Pharmaceuticals and Bio Pharmaceuticals. So we are engaging with our partners in CBER to be able to do that. So, you know, I just kind of wanted to highlight that piece. The other piece, two other things I just wanted to mention that came up during the discussion. One, you know, when companies come in and talk to us about advanced technology, typically, although not always, they do come in with a specific application type in mind. So, you know, those are company confidential type discussions. So we are limited or, you know, totally limited to the fact that we cannot share that information with the public in general. So, you know, we need to be cognizant of that. Also, the other point I wanted to highlight is that a number of folks have mentioned to me and the emerging technology programs that they are afraid to come in and talk with us. Because, you know, to a point that was made earlier, some may think that if they say something incorrectly, you know, we're not going to like it. And all of a sudden, you know, the discussion will end there and we won't want to continue that talk. Well, I can tell you being the person that heads up the Office of Pharmaceutical Quality and the emerging technology program being an integral part of that office, you know, we want to have these open discussions. We don't expect people to have answers. We just want to have a dialogue to be able to really start engaging. So I do encourage companies or individuals within those companies to come and talk to us. Don't be afraid, you know, if you say something wrong, you know, that's that's fine. You know, that's why we're having those discussions, you know, none of us are perfect. And I'm a perfect example of that. But we do need to encourage those discussions so that we can hear from folks. Also, if there are individual companies that are afraid to come in and talk with us, what I would suggest is that maybe a group of companies get together. And talk about, you know, they have a common interest in this technology, and then come present that to the emerging technology program or submit it to that program, and then they could request a meeting with the team itself. This way there may be a little more comfort in doing that. So, you know, we're open and we're flexible in terms of how we could interact with the industry. With that being said, I kind of want to just then give the closing remarks. I'm sorry I do appreciate the indulgence because I did just want to make a couple of those points as part of my closing remarks. As I mentioned yesterday, the Office of Pharmaceutical Quality held our biennial pharmaceutical quality symposium earlier this week so we have it once every two years. And this comment from that event really struck me and this comment came from somebody in the industry working with our emerging technology program to implement manufacturing innovations. And what they said is that the FDA is a barrier to implementing new technologies. And this, you know, I'm not exactly quoting but I'm kind of paraphrasing here, and they said that is because the FDA should be a barrier to implementing new technologies. Now that sounds kind of odd. But the reason why they said that is that we the FDA are first and foremost, a consumer protection agency, if you will. So it's our job to ensure that only safe, effective quality medicines then are available to patients and consumers. So I do want to put it in that context. So we're defining barrier on because it is our jobs you know again to protect the American public. So when it comes right down to it the most important thing is not how we're aware the medicine is made. It is that US patients and consumers benefit from the availability of those medicines I know there was some discussion. This is a panel discussion or during this did this open discussion, which preceded my closing remarks. Though we are not and we don't consider ourselves to be a barrier, part of assuring that quality medicines are available is making sure that there aren't also unnecessary regulation or regulatory barriers to implementing promising technologies, because we want to start to minimize our oversight, but the way to minimize that oversight by us is to make sure that we're at a quality level or quality management maturity level that that allows us the ability then to maybe inspect companies less and to back off from doing those inspections as frequently as we may need to. This is one of the incentives that we do try to stress often when we have these discussions about incentivizing people to look at advanced manufacturing, but not only advanced advanced manufacturing technologies, but just to enhance their quality systems and enhance the quality approach that they have within their own companies. So, however, at the FDA we are we are not always in the best position to know what promising technologies are coming for that matter to anticipate all of the regulatory hurdles that we might face so this is a new area for us. Hence the reason why we want to have these discussions. Hence the reason why we're here over the last two days with this NASA facilitated discussion, because we really do have to hear from from all of you so this provides that opportunity. We can't do it on our own and this is why I appreciate your help the reason why we're having these discussions, not only in this workshop but in a series of workshop workshops and events that have led us to this point because we've had similar discussions like this in other for So I value the spread of knowledge and experience that this audience has in the committee is brought to this important topic so I really do appreciate that from each and every one of you as well as from the NASA itself. One very significant thing to keep in mind as we draw to close is not only the mission of the FDA because we talked about I'm not sure there was an individual that kind of presented some of the mission statements of not only the FDA but also of other companies. What I really want to also mention is that this is just not the mission of the FDA you know we need to protect the, the public, we really do need to bring up the level of quality and this should not only be the mission of the FDA, but should be the mission of all of us and even some of us that are not here today that participate in this discussion. So that is to say we do not develop or might we the FDA do not develop or manufacture drugs. We only regulate those that do so I just want folks to keep that in mind. I don't always have the requisite experience or background or understanding or technical acumen that that we may need so that's the reason why we need to engage in discussions like this. I thought it was also telling in the polls that were showed earlier today and that were conducted yesterday that the audience thought changes in regulatory practices could accelerate innovation to some extent, while changes in industry practices would enable innovation to a large extent. I think what this shows is that like it or not we're in this together on and you know we're going to have to depend upon one another and deliver on our respective missions. So again, you know we keep stressing about interacting with each other talking about, you know, these issues with each other. So please I ask you, you know, to have no trepidation when you want to talk about this. Again, especially through the emerging technology program. That is part of my office and that is my commitment to make sure that we have these open and honest dialogues with you. And, you know, we're not going to hold anything against you. So in closing, I would just want to take the opportunity to thank Mason for putting this together, but the committee as well as the technical organizers of this these these workshops are never easy to put together and facilitate, especially when it's 100% remote or virtual. So I thank each and every one of you for being here with us virtually over the last two days, and hopefully we'll have more opportunities. And I'm looking forward to those opportunities to engage on manufacturing innovation as well, you know, because this is a topic that we are all clearly passionate about you can see how people really want to share their thoughts and ideas around this. So what I would ask is now let's take what we've learned and use manufacturing innovation to give patients and consumers more confidence, and better quality in their next dose of medicine that they take. So we'll leave it at that and again thank you for the privilege of your time over the last day and a half. Rex I'll turn it back over to you. Thank you, Mike. Thank you for those, you know, very positive comments and, and the openness to communication at all levels and in all manners of aggregation. We certainly encourage the community to follow up on it. And I do want to thank the speakers who've contributed really to make this successful meeting and, and of course all of the comments and questions there and responses to polls that the community at large provided to us. As Linda indicated earlier, the recording of these sessions will be released on the NASA website, relatively shortly. There is also in the queue a report in brief a written report in brief that will be issued. I'm not sure what the timing is of that do you know Linda. So the proceedings in brief that goes through a review process. And so we would be expecting a public report sometime in the spring. Okay. So, NASA and follows it's it's normal review processes, which, you know, take some time but in the meantime you certainly have will have access to the recordings. So thank you everyone for contributing to a really valuable session. We hope we have the opportunity to engage in various ways in the future. Thank you.