 This workshop will follow the release of a consensus study report sponsored by the Food and Drug Administration that identified innovative technologies, including manufacturing processes, control and testing strategies, and product technologies. Over the next two days, the pharmaceutical manufacturing community, including the audience will discuss the report recommendations and additional strategies to advance the field. So before we begin, I would like to thank the planning team that organized this event. Rex, Rex light us Sally Romero Torres, Kelly Rogers, and Tim shell of law. I would also like to acknowledge her sponsors the food and drug administration. Also, we greatly appreciate the support throughout the report process as well as this dissemination event. Thank you to our speakers and panelists for taking the time to attend and contribute to this workshop. We are all excited to hear your talks. And finally, I want to give a special thanks to the Academy staff. Brenna Elbin Jessica Wolfman and Eric, they have put a tremendous amount of work and effort to put together a virtual event that we all hope you will find engaging and fun. So, in the chat, we should have. If you know in the zoom chat, we have the agenda and the bios of the speaker for your reference throughout the workshop. In a bit, I'll also will go through some instructions on how to use Slido Slido is the platform that we'll be using to post additional comments, questions, and we'll also be having polling questions. So, this is going to be an interactive workshop. So I'm asking those who have their phone to take out their phone. And you can type in the Bitly Pharma Slido link onto the web browser, or you can pick your phone and use the QR code and just do it like so. The link to the Slido is also in the zoom chat. So once you go into Slido, you'll see there's a couple of options. You have the Q&A. This is where you can post questions. And the moderators during the community discussion may ask those questions out loud to the audience. You'll also see an ideas tab. This is during the different sessions, you can post your thoughts and comments in response to the speaker's presentations in the ideas tab in the middle. And then during the workshop, we'll also ask a few polling questions. And if there is a question live, you'll see a green button pop up and please feel free to take a moment to answer any questions. There are tailors to get you engaged with the workshop. And so we hope you have some fun with that. As with any chatting platform to be respectful of each other's viewpoints and be mindful of the language you use. We want this to be a safe and tolerant space. Great. So also, another note is for Zoom, there are certain rules of engagement on Zoom as well during the community discussion. Because of the number of participants out there to have some organization, we would like people to raise their hand to do that. You'll see the reactions tab with the smiley face go to that and you can click on the raise hand option and the moderator can call on you to speak. Also to note, as you are on Slido, as you type in your comments, if an audience member sees that comment they like it, you can upvote it on Slido as well and as more votes come in, the likelihood of your name being called is probably high. And so the moderator may call on you to elaborate further on your really good thoughts or comments. And also for further engagement and more engagement to look at your screen and speak review, which I think is on default already, so let's not worry about that too much. Alright, so let's do a Slido practice. Alright, so if you look on your phone, you should see, oh, you should see some questions pop up on the poll. It's the first question should be, which sector do you identify with? Alright, so you can just fill it in however you like. What level of engagement do you have at the report? And then we can see how many people are participating right now only 16, 18 people, 20, all right, so we're getting some of your good engagement, 25 people. We'll wait a few more minutes to get everyone up to speed and practicing. So with that, you can kind of get an idea of how we're doing. We have about 36% coming from the biopharma industry, 21% coming from government. You can see the number shift. And again, this isn't used for any data collection from the Academy side. This is nearly to get people engaged. Oh, wow. Excellent. 60% found this report very relevant. So for those who have dual screen or feel more comfortable using it on the computer, you can use Slido on your PC, Mac, and other desktop platforms. All right. And so, without further ado, I will move on to the next section. I would like to introduce Rex Rathlitis, who is the Burton and Catherine Gedge distinguished professor of chemical engineering at Purdue University. He also served at the tier of the consensus study and will begin our day by sharing some of the final conclusions and recommendations from the report. Enjoy. Okay. Good morning. I was on mute. So what I'd like to do is to briefly recap for you the principle findings of the study that was released earlier this year. The purpose of our meeting really today and tomorrow is to really to draw on your feedback to the report to get a sense of, you know, given it what has transpired over the past year or two. We really need to look at other technologies. Are there other issues that have emerged. And so it's very important for purposes of validation for the FDA that we have your input into this report. The meeting will also provide the opportunity for our colleagues in the FDA to convey to us some of the steps they've taken and some of the reactions they have had to that study. So let me just very briefly recap for you the contents of this study. First of all, you have many times heard from the leadership of the FDA that there is a need to achieve a flexible agile manufacturing sector that can produce high quality drugs without extensive regulatory oversight. And clearly what has happened in the last two years emphasizes the need for such innovation. Now in order for that to happen, we need to of course enable innovations in pharmaceutical manufacturing. And unfortunately, while there has been a lot of progress that progress really hasn't been as rapid as many of you and I would like. So for that reason, the FDA has commissioned a study, and that that study was to be managed by the National Academy's team with the purpose of identifying emerging technologies that have the potential for advancing pharmaceutical quality and modernized manufacturing to describe some of the technical and regulatory issues associated with those innovations and then recommend how to overcome some of the regulatory issues to facilitate adoption of that, that technology. So, the Academy has taken that chore on, and in its usual fashion has put together a committee, which I had the pleasure of serving. It's a committee that has representatives from academia from various government agencies as well as from the Gates Foundation. And of course it was supported by the NSF staff. Now, what we did is really convene a number of workshops and web access with members in the community to really try to identify the innovations that the FDA is likely to see. And the important part is our chore was to identify as those that are we're likely to see within the next five or 10 year horizon, not necessarily what we would like the community to pursue. Secondly, while we recognize that innovation requires all stakeholders to participate, the purpose of the study was really to focus on the role of the FDA in preparing for and facilitating these innovations so our report did not address our expectations of the stakeholders it was focused on the FDA. Now, of course, the key topic here was the innovations themselves, and the committee chose to divide those into four rather obvious areas to drug substance drug product, and then some of the enabling technologies like automation and control and innovation and manufacturing networks per se. Now, there's certainly a large inventory of such technologies that we looked at and reported. We really are not going to go through all of that right now. I'll just highlight a few of them. And the next couple of slides. For instance, in the area of drug substance. The committee felt that the new routes to synthesize new drug substance such as electrochemical or photochemical or bio catalysis routes are really going to be very important over the next few 510 years co process active pharmaceutical products, likewise, and of course process intensification in order to create more efficient processes in particular to create processes with smaller footprints that these are in a really important engineering and technology developments. Additionally, as in much of manufacturing in general, the feeling was that additive manufacturing technologies which can allow Taylor and customization of drug products. Again, is a really a very promising avenue that that we expect to see more innovations all of these technologies require advanced process control and automation. We need real time of process optimization automation capabilities, of course, digital twin is one instantiation of that. Finally modular systems that offer the possibility of creating distributed manufacturing system that are flexible integrated and readily brought online. So just very briefly those are some of the key directions of course there's a lot more detail in the report, but I just wanted to highlight those. So that's the technology part and then the second part, very important part was really what have been some of the challenges that are imposed by the regulatory process for innovations to take root in the industry. So there are basically five areas that the committee highlighted the product technology review process itself, the alignment of incentives for manufacturing innovation, global harmonization, post approval change and then the FDA internal challenges and I'll briefly highlight just a little bit about each of these five areas, beginning with the tech with the review process. As you well know, under the existing regulatory process, the only way and new technology is reviewed is through in the context of an individual product review. And that really places a significant burden on the manufacturer who introduces that technology because there is the risk associated with the new technology and the risk associated with a new product. And the feeling from the community and and really reflected by the committee was that unless there is sufficient incentive for a manufacturer to bear the possibility of costs and and time delay because of manufacturing concerns, there really is much of an incentive just to stay with conventional technologies and not introduce new technologies. So, that basically points to the fact that there needs to be an alignment of incentives and it was pretty clear from the interaction our committee had with the community that, you know, this is a really key area. It certainly is clear that if there is no other way to get a new product manufactured, other than through in that technology then it's obvious there is a business incentive to do so. The problem is in areas in which that technology really could have an impact on a whole portfolio of products. It still is the case that that first product that uses the technology has to basically bear that double risk. It is, of course, likewise for existing products where every such existing product now would have to be re approved in the context of a new technology and that creates again, kind of a business disincentive. So, and some in substance the committee found that although, you know, technical regulatory challenges pose significant hurdles, none of these challenges presents as great a barrier as this issue of incentives. So, that means there is really needs to be an active effort in trying to align stakeholders to come up with processes and and avenues that will allow us to basically, you know, align incentives and therefore drive new manufacturing ideas. Next slide. The other issue that's that's really key is that of harmonization. It is clear that that the manufacturer of every new product would like that product to appear in globally and various geographic regions. And it is equally well known that the regulatory expectations of the international authorities really are quite diverse and they pose a challenge. And that challenge is even multiplied in the area of new technologies. So, the committee clearly heard from the community that any progress that can be made to accelerate regulatory harmonization and consistency will reduce this incentives for global implementation of new and exciting technologies. So global harmonization is really a very big key issue. Further challenge is that of post approval, as the community is well practiced to experience, you know, every manufacturing change of a product that's already been approved. If it is significant enough or requires regulatory approval. And that certainly is required of new technology and that provides kind of an impediment. And then a guidance ICH Q12 that looks at the product life cycle and really has some good ideas on how product improvements can be advanced, but the key is how will that guidance be applied and utilized by the various bodies. It's clear that there needs to be incentives put in again to encourage taking existing products and moving them to new manufacturing platforms. Finally, the last challenge is really within the FDA itself. And certainly the committee appreciated that the FDA has taken really important steps to encourage innovations to foster innovations. However, the views that the committee collected from the community indicated that the role of Cedar and enabling innovation is underdeveloped, and that this underdevelopment really jeopardizes the ability to use new technology to produce safe and efficacious drugs reliably. And some of these challenges, I'll enumerate a little bit more in detail in the next slide. And first of all, it's a matter of having the expertise capacity and the culture within the organization to really be able to do with new technology. And that's a significant challenge for the staff to really stay up to speed with the newer things that that are coming along the line and it's a challenge for the organization to basically have training. The capacity constraints in dealing with new technology are perceived to be significant enough to affect the consistency and evaluating new technologies. And philosophically, there is really a dissonance between oversight to assure safe products, and then the facilitation to encourage new technologies. And we have to find effective ways of breaking down that dissonance. Clearly, the community feels that with new technologies, there are significant new risks and uncertainty is how the FDA will react to it. And that applies to, for example, the data requirements required for regulatory filings for clarity and consistency and evaluating the residual risk to product quality, and of course, the issue of global regulatory environment. So these are really important external kind of perceptions of the community that needed to be highlighted. The next slide is the committee recommendations I have a couple of slides to go through. First of all, the obvious recommendation is to strengthen the expertise innovative technology throughout the organization, and to look at internal mechanisms so that staff can be exposed to new technologies and to hire people that are already educated in those technologies. So that's really a key requirement and a challenge. Secondly, next slide please. The committee clearly felt that the emerging technology program is really be a remarkable success. It's very well received by the community. However, the committee likewise felt that the scope and capacity of the ETT program really needs to be enlarged. And in particular, that it have dedicated independent funding be able to expand and have dedicated staff for that function to broaden the criteria for entry into the ETT program, and to increase the transparency of the capacity of ETT and the program outcomes. This issue of transparency is particularly important so that it could be learning across the community of the activities that ETT undertakes. Next slide. Of course, the flip to the next slide please. Clearly, the leadership role is a very important one and CEDR is engaged in ICH guideline preparation, but the committee felt that CEDR really needs to increase dedicated resources so that the FDA could be a leader in encouraging and accelerating harmonization and how new technology is really accepted. Finally, it is clear that we have focused on the activities and the resources at the FDA, but it is equally clear that this is a community activity that it really getting new technology and is everyone's job, it isn't just the FDA's job. Last slide. So, although there is no one that really has control over it, however, the community needs to participate, the community needs to be engaged, but the FDA really has a critical role to play. It has direct leadership role and needs to support the ability and willingness of manufacturers to lead and drive innovative change. So, that was really the summary of our report. And at this point, what I'd like to do is to invite some of the members of the committee who participated in the study to offer their comments. Any other questions from Kelly? Yeah. Thank you, Linda. So Rex, thanks for the summary of the committee's work. And I think that the timing is an important thing to point out to this community that the committee started its work before the pandemic. And the recommendations that were made for what technologies would appear in the five to 10 year timeline were really pre-pandemic concepts. And so I wanted to point out to this community that one of the things that this workshop is intended and hoped to elicit from the community are areas in which the pandemic has accelerated the timeline for when technologies would hit. And obviously the mRNA vaccines are one of those areas where the pandemic has definitely changed the timeline for having commercial applications. So, I just wanted to invite the community to think from that lens that really the technologies were pre-pandemic in their nature or in their assessment, I should say. Matt, did you want to add a comment? Good morning, everybody. Thanks Rex for the really fantastic introduction. I actually don't really have too much to add, but if a colleague here would like to add something, I'll give up the time for that. I'm actually running on my way to teach bioprocess engineering this morning. So, teaching the next generation, some of the topics that we'll be covering here in the next couple of days of the workshop. Okay. Well, thank you. Go ahead, Todd. We're having a hard time hearing you. A little difficult to hear. Still can't hear me. Oh, perfect. Loud and clear. I just wanted to comment that was a great summary, Rex. I think one of the things that we need to recognize is the world really is changing rapidly and setting these challenges to innovation also in the context of the now recognized ability and extreme pressure to move extremely quickly in manufacturing. And the time constraints from a manufacturer's perspective, and their willingness to bring on board innovation may add even additional pressures and make these barriers seem larger than they might have seemed prior to the pandemic. Very good. Thank you. Arlene has her hand raised Arlene, would you have a comment? Yeah, sure. Thanks Rex for including me here. Again, and I'm Arlene Joyner I work with Health and Human Services in the agency called BARDA. And I wanted to really add on to what Kelly mentioned so the study we did was prior to COVID and the pandemic response but it really, I think COVID became a case study because we really relied on, you know, quick manufacturing of vaccines and I know the study was focused a lot on cedar products and small molecules but from a BARDA perspective it's very similar in that we're always looking to be able to respond quickly to any public health emergency, you know, a CBRN incident where product needs to be available quickly. So these innovations I think are really important that the private sector company is working on. So we encourage the company, you know, the two main outcomes I think from the study were having the private sector companies and communities work together, you know, collaborating and helping it so that the FDA from a regulatory perspective is not having to work with one company at a time right so can they develop regulations and policies that address a group of companies as opposed to one at a time. And then at the same time we saw through pandemic response that the FDA is very collaborative we have many many early on conversations about the technologies that were coming up with the vaccines, how we can expedite things what can be done, or what their requirements are in order to get them through the process as quickly as possible so it can be done. We don't necessarily want to have a pandemic be the reason things happen so well and so quickly, but actually it was a good case study to show that these innovations are important. And then we can work with the regulatory agencies to get them through quickly and successfully. So, thank you. Thank you Arlene. Well, did you want to contribute your comments. Well, thank you Rex. That was a great summary. So, my participation with a group is really based on my experience from outside of farm circles. I worked for many years in consumer products industry with the solids processing in less regulated contexts. The perspective is that the cedars encouragement of the use of continuous processing over the past, say, 15 years or so I think it's been a had had a positive effect. It has encouraged innovation in the industry. And I think it, you know, it's a, it's a good stepping stone to some of the recommendations in the report, specifically looking at how we can go from continuous flow and processing to a more end to end, you will be able to flow in, in the production of the, of the product. That means we may need to flow across substance and product regulatory barriers. Right. This is a challenge. Process intensification and modularity you mentioned. And the process controls that are associated with them are important. And all of this is having stable processes with inline controls of the short product quality. And in this aspect, I'm a little bit concerned that the broader community, maybe have become a little bit overzealous in its embrace of the word continuous. Right. The root cause of the focus should be on process stability and control. If you can do that with continuous, that's great. But there are cases where small batch or fast batch turnover may be inherently more stable in terms of the use of continuous rolls. And we shouldn't, you know, discard that just because it doesn't have the right label, we have to get, you know, more consistent vocabulary that uses words in the right way so that we avoid some of these kind of conflicts or dissonance that you mentioned. Beyond that, I learned an awful lot about the drivers for product innovation and working with the group and and how those affect pharmaceuticals. And I think the committee's report is really well timed to help address some of the more recent supply chain tensions that Kelly brought up in regards to the pandemic. And, you know, there's plenty of opportunities to innovate going forward so thank you for. Thank you Paul those those are great comments. Does anyone else from the committee want to offer some words of wisdom Sally. Yeah, thank you. Can you guys hear me. Okay. Excellent. Excellent. Thank you. Yeah, so I mean to me that the writing the report was of course a great experience but I think that the angle that I, or did I mention that I was actually looking at the report was more from a change management perspective. I think that we do have, we do have a lot of talent in our industry. So I think that there has been a little bit of confusion with regards to how we organize, you know, the concepts and the language and how do we transmit those in such a way that we can use them, and use them within the quality systems that we have right now and within, you know, the infrastructure that we have. So to me, you know, and I think that this goes a little bit to what Professor Ward was mentioning is what's going to be our main goal, what's going to be our, you know, our value proposition or what's going to be our angle for, you know, our customers and our patients and then just focus in how do we get there by leveraging new technologies and perhaps learning from other industries. And at the same time, how do we make our industry comfortable enough and translate certain engineering concepts and quality concepts that are happening in industries that are performing at that six sigma level practically to our industry just to deliver better products and to deliver more to our patients. Thank you so much. All right, thank you for those comments. Anyone else on the committee Tim. Rex, Tim Shalewa and I was really appreciative Rex of your comments and summary and also, you know, thanks to the academies and to the committee, you know, for the privilege of participating in this it was really a great experience. I learned a ton and I was actually a part of Pfizer. And with responsibilities and technology and innovation throughout the course of the study and the writing of the report and have now retired from Pfizer and joined nimble, which gives me a chance to sort of translate my efforts, you know, on behalf of Pfizer into a broader community benefit. And, you know, because nimble is charged with bio manufacturing and technology and workforce innovations. And I just wanted to, you know, use this time but to quickly talk about the workshop for a second and what we're hoping from all of you. I mean, because the purpose Michael, my copter will be speaking and he'll be talking about this also but I think it's important to remind ourselves that the report was sponsored by Cedar and we were asked to make recommendations to Cedar, which we did but there are also observations in there that that speak more broadly to the community and Rex mentioned this that it's really important to look at this not only from a, you know, what can FDA do, although that was the purpose of the report, but I hope that this workshop is you know, causing people to, you know, who have voted with their feet a little bit and their time to come to this workshop to think about their own responsibilities to the community as as leaders in the technology and innovation space for pharmaceutical and I'm hopeful over the course of this workshop that we will get the kind of engagement and ownership as, as Rex said, to think about what we can do collectively I really, you know, in the report it, it mentioned the need for a system based a focus system based effort. And I think it's really important that we all consider our own our ownership responsibilities to that system and our leadership responsibilities, but I think it's going to take a cohesive effort and, as people have mentioned the and highlight that have been highlighted in supply chain deficiencies over the pandemic, you know, really, you know, cause us to to to re recognize and need to re energize that our community toward toward enablement of innovation that will benefit, you know, not only the companies but patients. And I think it's really important so thanks very much for the opportunity and please as you engage over the course of this, you know, listening and and speaking, you know, please think about, you know, how you can help. Thank you, Tim. For for the attempt to rouse the community in the collective action. That's really important and I think that's a theme that actually came through a lot of the discussions is that, you know, rather than individual players advancing technology is recognizing the technology is a tool to enable good products. And we can share in the tools, and we can differentiate ourselves or how effectively we use the tools, but we won't differentiate ourselves on the tools themselves. And if we keep that in mind and that can provide the incentives for putting together consortia and, you know, collective activities to really advance technologies that will that will benefit patients so I think we we need people like Tim here to to organize the community and drive them forward so Tim you're not allowed to retire. We have a few questions coming in from Slido. So, one of them with a couple of upvotes is from Narendra van. He asked, can we create a regulatory incentive for key manufacturing technologies that will advance the whole field, similar to break through status. Very good comment with anyone on the committee like to address that. Or anyone in general raise your hand and we'd be happy to hear your thoughts. Silence is always a little bit more amplified on zoom. Oh, Tim has his hand up. Okay Tim. I guess I'm off mute. Thank you. Yeah, I think this is a great topic great question. As far as the structure of the agenda, it's probably a good topic for for the session for discussion Sally. You know because we're really talking about solutions, you know in session for and you know this this seems like one that would be really good to give some time for discussion there. Thank you for that Narendra. It also looks like Jean, Tom has a couple of votes on her comment as well. For the FDA. How will the FDA engage the industry as a whole rather co by co the IQ consortium should be leveraged. Jane, can you elaborate a little bit on that comment. Yes, can folks hear me. Yes. Okay. So the question is, how would the FDA engage the industry as a whole rather company by company. There is a, what's known as the IQ consortium which has some 60 major pharmaceutical companies as members whose focus is I'm trying to figure out how can we do things better from both a regulatory and technology point of view. So, you know, it's just throwing it out there maybe it's more appropriate for one of the later sessions but I would be interested to hear how that how the FDA would think about engaging the industry as a whole. I think it sounds great when you say that but what is the mechanism to do that. Yeah, very good point. Kelly, did you want to respond. Good. Yes, thank you. I just wanted to thank Gina for the question because that really cues up our next session and we are going to have speakers, Larry Lee and Joe Welch in that section, which is on existing mechanisms to enable innovation. And so I feel that that question really validates the organization of this workshop and the opportunities for the community to really put on the table what do we have to work with and where are the gaps. And so I look forward to that discussion and I'm hoping that Jean's okay with being a little patient until after Larry and Joel have had a chance to speak to that. Very good. Thank you. One more question coming in from Laura. Was there any broader discussion of trade off between data produced for a new process versus that produced for a broadly understood and established process. Anyone would like to respond to that from my recollection I don't recall that there was an explicit discussion of that issue. However, the issue itself was raised and the fact that that's part of the uncertainty, given that you have a new process, what new and additional information do you have to provide in order to provide assurance that that not only is the product. doing his job, but the process is reliable as well. And, and that is that is a very key source of uncertainty for the community at large and certainly we hope that we evolved to come up with solutions for that. Sally, would you like to elaborate. I can add a little bit into that I think that, you know, like we, we did mention some something that it's just a, it's a good practice it was just a song, you know, you can you can have tons of data but you also have to have knowledge and product knowledge so I think that, you know, this this question it's more aligned with best practices and I think that we did mention it in the document that what we foresee it's that. And I think that this again this is just something that the FDA has also mentioned throughout their guidance is is that knowledge pair with data. It's more powerful just data alone right like you have the purple portion but then you have also the fundamental part and that combination it's what really is going to drive value. I don't know if that answers a little bit to that but we can, you know, we can add a little bit more later, and in the other discussions. Yeah, no that's a that's a very good, good point that and certainly us in academia always value the knowledge part. As a framework for within which to present data, because the data ought to support the knowledge, but, but how to do that in a, you know, in a measurable fashion is difficult right it's a qualitative assessment unfortunately what the level of knowledge is. Great, do we have any other comments or questions. Linda that has popped up. So far, no, no other questions is on slide out but for those who came in a little late, if you look into our zoom chat box. We have the links to slide out. Which, if you click on it from your computer I'll take you to a screen where you can post your ideas and comments. And then we'll get right to it based on session topics. But I think you know in about 10 minutes we'll have Mike from the FDA come up for opening remarks. So, Kelly is Linda I just wanted to point out that in the question and answer session the slide oh, there's a question there as well. Thank you. Sorry, I'm being me on a drone and I apologize if I mispronounce anyone's name. Yeah, they asked how is approaching the S house approaching FBA the introduction of artificial intelligence tools in the pharma manufacturing process. And any responses to that question. Sally. Yeah, Linda just just for context, can you repeat the question again. Yeah. They asked how is approaching FBA the introduction of artificial intelligence tools in the pharma manufacturing process. So I guess it's asking how's the FBA approaching using artificial intelligence in the manufacturing. Yeah, I mean as a committee member I don't want to talk too much, you know on behalf of the FDA I can talk on just what I have seen in prior guidelines that they have been supplying into our industry. I think that we have to be careful with the term artificial intelligence because we have been doing artificial intelligence for many years already. Every time that we have a like a control loop every time that we do data analytics and we use like multivariate analytics. So it really depends on the algorithms like PLS PLS and PCA which we have been using for many years already. That it's part of artificial intelligence. So it really depends on which artificial intelligence tool that you know we're talking about. And again, many artificial intelligence, there are many shades and colors for artificial intelligence so for what I have seen in my humble opinion they have been promoting it, especially when the deadline came out. And there was a lot of talk about you know like new sensors and then you control mechanisms that are using more like you know multiple information to make decisions of course that information needs to be mind. And usually the way that we mind that data is using machine learning which is part of artificial intelligence. So I think that they have been promoting it it's not that it has been called explicitly artificial intelligence. So we can elaborate on that certainly within the report. We included a fairly extensive discussion of machine learning and artificial intelligence applications within the automation and control framework. And it is a component of lots of hybrid models where one combines first principles, where you use a first principles model where you know the first principles that combine it with a machine learning model where you don't quite sure the first principles yet. And that kind of hybrid framework is really I would guess part of most digital twins that that people are contemplating because we never have all of the first principles knowledge on the table. So AI is, of course, a broad term. But, but I think probably for the kinds of applications we're thinking about machine learning is probably the more correct decision because we're, we're, we're making using it as a tool for making quantitative decisions rather than qualitative ones right. But that was a very good issue to raise and and certainly the committee spent some time discussing that, that new technology, or that new not so new technology. In the last couple of minutes, we have one more, and it's from soup soup song Q. They asked how will the FDA bring seabird to the same page, especially in pharmaceutical manufacturing of vaccine and new modalities. Another Mason study for seabird. Thank you. We really can speak to the FDA and and we certainly can speak on behalf of Cedar on what CBER will do. But you know it is fair to assume that at some point, the initiative that was shown by Cedar will be picked up and and follow through by CBER as well. But as you, as you well know, our study was sponsored by Cedar and so we limited ourselves to the issues within the Cedar portfolio. But we certainly would have loved to have broadened the study, but you know that was set by the parameters for for our task. Well, I think if we have no further questions. Linda, perhaps we can switch over and begin our next presentation is Dr. Cops online. Yes, I'm here. Thank you. Let me just take a few minutes to introduce you, although, you know, you are certainly not a stranger to the to this community. Dr. Cops is director of the FDA office of pharmaceutical quality. And as you well know that's a large organization with very broad responsibilities that really touches on virtually every type of human drug manufactured. And so it really has an enormous scope. To his job 25 year experience in the industry, including serving as vice president of Novartis computer health. He has educated in pharmaceutical sciences and, and certainly, you know is a is a great alumnus of Rutgers University. And, you know, we're happy to have him address us and kick off this workshop. Dr. Cops. Thank you so much Rex I appreciate the kind words. Also, I just want to comment that I do appreciate all the enthusiasm with the questions that have started already. I'll answer a good chunk if not all of the questions that were brought up so I just ask you to bear with us as we go through our presentations and then as we engage in discussion, because as was mentioned earlier this morning. I really want this to be, you know, a discussion back and forth, because we really do want to get the feedback we do want to put our views on this area of forward as well. And we will continue to advance in advance manufacturing. So, as you can see from the slide, the topic of my talk today is advanced manufacturing and the future of pharmaceutical quality. As Rex had mentioned I am the director for the office pharmaceutical quality I've been in that role now for just about the middle of next month it will be my six year anniversary in this role. It's been a lot of fun being in this role. And I've enjoyed the opportunities today being one of those opportunities to be able to engage, not only internally within Cedar within the FDA but with the industry and our stakeholders as well with patients and consumers. Obviously, being an important piece of that engagement. So what I'm going to do is if we could move to the next slide. I'd like to start my presentations by sharing with people kind of my view or my definition of pharmaceutical quality just to kind of ground the group. I'm in an easy way to remember pharmaceutical quality, because when we talk about quality of any product, whether it be a computer, whether it be a car, or a smartphone. I can usually tell you what that quality looks like. However, when it comes to quality of pharmaceutical products, folks kind of stumble a bit in terms of how to try to define that. But quality of any product consistently meets the expectations of the user I think that's simple enough. And drugs are no different if I could click on the next slide. Thanks, drugs are no different nor should they be so in a general sense, this is, you know, kind of a way to look at a quality product. Because it does span across all of these products including drugs. Next slide please. So patients expect for for drugs them to be safe and effective with every dose that they take. Next slide please. So pharmaceutical quality for me then an easy way to define it is that it ensures that every dose is safe and effective. It's free of contamination and defects as well. Next slide. So it's what gives patients confidence in their next dose of medicines when you take the next dose, you are assured that it will be safe and effective. So when we talk about drugs people usually typically talk about safety and efficacy, but there is a third component of that that is understood and that is quality so when I talk about drugs and talk about safety, efficacy, but predominantly my focus because of the role that I'm in does focus on the quality of that medicine itself. Next slide. What I'd like to do then is to give you a little bit of an idea of the outline of my presentation today so I want to talk about innovation in the changing world, the challenges and opportunities that face each and every one of us in this area. The importance of advanced manufacturing, as well as the regulatory framework so we'll start to get into hopefully answering some of the questions that were brought up a little bit, a little while ago a little bit earlier this morning. Next slide please. So we keep hearing this phrase the new normal associated with COVID-19. Many of us think about that is taking steps to protect ourselves and others from COVID-19 typically through wearing masks, vaccination, physical distancing, things along those lines. However, what I'd like us to think about today as well as tomorrow for the two days of this workshop is how we can use innovation to better equip ourselves to handle an ever changing world. And when I talk about ever changing world, one of the things you'll hear is what's called a VUCA world, V-U-C-A. And that stands for volatility, uncertainty, complexity, as well as ambiguity in an ever changing world. So we need to address those issues or at least be aware that those issues are out there as we look at the world or as you know, as we look externally to see what's going on on a global scale. Next slide please. So COVID-19 is a virus that infects humans, but it affects nearly everything else that we do, including pharmaceutical supply chains, customer demands, you see all of that going on. It's in the news every day now and decision making that's based on science and research or science and risk I should say. So it's always a risk based but science driven evaluation that we need to do. So from one viewpoint though, even prior to COVID supply chain disruptions have been their own kind of contagion. So what do I mean by that the best way for me to define that is to use a common story that I think all of you hopefully would be able to relate to. So, for example, there's an issue. Let's let's say it's a quality issue, which forces a manufacturer to temporarily shut down operations. This issue then spreads as does an infection to other manufacturers of their products who are forced to scale up to meet market demands. This issue then spreads to patients and consumers who lose access to their drugs when the remaining manufacturers can't respond quickly enough, or in some cases can't even respond at all. So we need to use the same type of innovative thinking to realize a future where we focus on becoming immune to supply chain disruptions. And those are the kind of things that we really want to start talking about, and advanced manufacturing is one of the ways to address that immunity and I put that in quotes obviously, if you will. Next slide please. So we felt it was important we us at the FDA more specifically those within the office of pharmaceutical quality we felt it was important to share a vision for this future of the future of pharmaceutical manufacturing. I love to do wordplay so I ask you to bear with me a little bit. The dawn of the fourth industrial revolution forces us to visualize what a fully digitized and autonomous manufacturing world looks like in industry 4.0. So there will be new operating paradigms as a result of this digitization, automation and real time data integration. We need to start better understanding and I think you know this has been brought out in the report that they some had issued, as well as some of the opening discussion you heard today we need to start better understanding how this new manufacturing paradigm can impact pharmaceutical operations and the regulatory piece of that as well. And we'll share with you not only today but tomorrow in terms of how we're starting to craft that regulatory framework. We shared this vision in a paper we published earlier this year on industry 4.0 you see that paper in this slide. If anything I think COVID-19 accelerated the need for industry 4.0 technologies I don't think there's any argument there. In order for us to be responsive to rapidly changing demand and to reduce dependency on human innovation. So whereas industry 3.0 saw rapid advancements of individual operations and tools industry 4.0 promises advancements of entire manufacturing systems. The journey from single data collection to digital maturity is one in which data transforms from raw data that is captured from a manufacturing process. And when it's captured in that process. It's to help us inform to be informed by the analysis of all of that data that we now have also to the knowledge form through the addition of contextual meaning, perhaps by artificial intelligence I know some of you are interested in that area we just saw a question earlier today. And finally to actionable wisdom to inform decision making by the contribution of insight that has gotten from that type of an analysis. So it is this wisdom if you will, that fuse fuels the autonomous systems capable of self self optimizing doing decision making movement of materials, as well as adaptive controls. Next slide please. So the essential feature of an industry 4.0 environment is the integration of connectivity, artificial intelligence and automation to enable systems then that operate with little to no human involvement. So these cyber physical systems if you will can fuel real sorry confuse real time and online data with industrial production, as well as artificial intelligence in order to optimize manufacturing as a whole. For example, external information, including patient experience and supplier inventories could fuse with internal information, such as energy and resource management. So we're able to really make better use or more holistic use of the information that we have. This integration of internal and external data source source is then enables us to be in an unprecedented position where we can have real time responsiveness monitoring and control of what's actually being done. And the result is a well controlled pharmaceutical value chain or supply chain for the manufacturer, one which also benefits ultimately where we all need to be focused on patients and consumers. Next slide please. Thanks. We are now at a point in history where challenges have created opportunities and these challenges always create opportunities. So you know we're always concerned about change, but when there's change that creates an environment for new opportunities and we need to seize that those opportunities well we need to seize the change, and then also come up and take advantage of the opportunities that are presented. So these challenges spur innovation, they drive us to be better and to stay better and to continuously improve where we are. Next slide. So the White House published a 100 day report on supply chain. And what was said in there and I just want to take a direct quote that the three pillars of a secure and robust supply chain are quality, diversification and redundancy. And you see the first word that they they highlight for the robustness of that supply chain is quality. Drug shortages, however, do still unfortunately happen. We've published on this we've talked about this I've presented on this a number of times that more than 60% of drug shortages are attributed to quality related issues. So traditional manufacturing relies on large factories I think we're all well well aware of that with needs for affordable labor, which concentrates in areas that can support these needs. Traditional manufacturing technology cannot respond at agile Lee to rapid changes such as during a health public emergency on such that we're in right now. Next slide please. So we've been challenged to develop a framework. We've been challenged to develop a framework to measure and provide transparency into a facilities quality management maturity, or since in the FDA we love to use acronyms quality management maturity. I will refer to as QMM. It's not something out of a James Bond movie but it is, it does define quality management maturity. QMM is a state attained by having consistent, as well as reliable and robust business processes to achieve quality objectives and to promote continual improvement. So we need ratings people were talking about how we're going to measure this how we can incentivize the industry. Well, we are, we are developing a rating system to determine the maturity level of a company, you know, in their quality systems. So we need these ratings that recognize and reward manufacturers for having more mature quality systems that achieve sustainable compliance and focus on continual improvement. So the bottom line of this then is that we need to incentivize improvements to the pharma manufacturing infrastructure that enhances the reliability of manufacturing, and ultimately the supply. Next slide please. Of course, part of investing in quality and continual improvement is adopting new technologies. New technologies can't be adopted without a business reason, and we understand that Rex had mentioned that in the beginning. You know, there is a startup cost associated with these new technologies, and there is some trepidate there is some hesitation and trepidation in terms of switching over from these conventional technologies to new advanced manufacturing of footprints. So it turns out that in many cases advanced manufacturing can be more cost effective after the initial startup cost, then traditional manufacturing. Next slide please. Next slide. Well, as we move to the next slide, I will still continue. In fact, advanced manufacturing is a key component of the overall US strategy to strengthen domestic drug manufacturing and increase the domestic supply of quality products. And it may finally help take our manufacturing capability above six Sigma, and this is something that that is a target that we really do need to shoot for and that we really do need to achieve over time. It can also enable us to develop drugs rapidly and prevent drug shortages. As the coven 19 pandemic has certainly taught all of us and I don't think there's any argument here, agility and flexibility are needed to maintain pharmaceutical quality in a public health emergency. So while the upfront costs can seem daunting, as I mentioned previously, advanced manufacturing can ensure higher quality and consistently available medicines. I was going to say next slides but I think two slides ahead now. Sorry, Mike, we're having a little technical difficulties. That's okay, I can still continue to, to, you know, kind of go through the presentation. When you get caught up. You know, well, the slides will catch up to somewhere along the way I would hope. So the situation is similar for regulators. There is a startup cost as you could imagine. Understanding and evaluating the new technologies. So that was mentioned before you know we've got to learn. We've got to train ourselves train our staff. I'm train our inspectorate as well to be able to deal with these new technologies because while we talk about them, we have to regulate these technologies as well. However, the payoff for us as regulators is a big one. And that payoff is a more reliable industry requiring risk less regulatory oversight. Because I think the industry as a whole will be more than happy to see less regulatory oversight. You don't have to see us coming in say hi we're from the government we're here to help you. So, you know, we really, you know, could put our time and intention in terms of doing other things. But that is our ultimate goal to have less regulatory oversight. So that is another incentive, although the industry may or may not directly realize that it is an incentive to getting into these advanced technologies. If we could just advance one more slide 18 I think we'd be caught up and then it'd be in good shape. Thank you. So, part of our regulatory set startup costs, with the series of workshops. So, Nathan, which which Nathan so jointly held, as was noted this was done or sponsored by Cedar, not by CBER, but I will address that question in my presentation that we are partnering with CBER in the area of advanced manufacturing and I will highlight that in my presentation in a little bit. So the committee that Nathan put together on pharmaceutical manufacturing innovations, taking a look at what's on the horizon, and the thorough consensus we support support, sorry study that's available online. Of course, we really do need to see what those technologies are in five to 10 years out. So as we look at our regulatory framework, we could put a framework in place that can deal with the future. But it's not going to be outdated as soon as we start up, you know, putting in or making some changes to our regulatory framework. So we want to be ahead of things by five to 10 years. The benefit of more reliable medicines will be felt by consumers and patients. So everybody wins when we do things like that. Next slide please. Basically you know that FDA has long supported investments in advanced manufacturing, it was noted in the opening remarks this morning as well. And the reason why, you know, we support advanced manufacturing is because they provide a safe and more secure drug supply chain. So advanced manufacturing is not a futuristic approach that you see in science fiction TV shows or in movies. Advanced manufacturing is already providing quality products to patients and consumers. We do have several initiatives, which have made this possible and we will continue to make this possible in the future as well. Next slide please. Later in this workshop you'll hear about some of our advanced manufacturing initiatives which include the emerging technology program or ETP. We are moving this to the next iteration or the next version. And we'll talk about that as well. We're going to talk about the framework for regulatory advanced manufacturing evaluation, which is called frame, the acronym for that is frame AME. And we'll talk about that as well we love acronyms in the government so you know this one you know ETP we got frame, which which again follows with with the use of those acronyms. And the third one is the development of an advanced manufacturing science and research program. And again we will talk about that over the next two days. Next slide please. In 2014, Cedar established the emerging technology program to provide potential applicants and opportunity to discuss identifying resolved technical and regulatory issues. The major milestone for this program was the 100th 100 FDA sponsored emerging technology meetings. So that avenue is being very heavily used by the industry. Of course the technology cannot be emerging forever. And another recent significant milestone was the first graduation from the ETP. So we graduated from the emerging technology program to put it then into the mainstream assessments that we do when sponsors send an application, and that technology is continuous direct compression or what we call CDC. This is the Center for Drug Control, sorry disease control, but it is in this context it's the continuous direct compression. CDC is a pharmaceutical pharmaceutical manufacturing process that consists of dispensing mixing and compressing using equipment that is integrated, resulting no breaks in the process so it's a continuous process, obviously. CDC can improve the assurance of product quality by minimizing human intervention, as I mentioned earlier, and taking advantage of process analytical technology or what's what's another acronym for you is PAT. So the emerging technology program graduation is an important step for us in the life cycle of the technology. The reason being that it signals FDA's confidence in industries ability. The confidence we have then an industry's ability to successfully submit applications utilizing that new technology. It improves the OPQ's efficiency and assessing applications, and also increases our capacity, then to evaluate other more novel technologies. So we really do want to then continue to graduate these technologies into the mainstream review work that or assessment work that we do. We continually receive new technologies and graduate them as they become more mature within the ETP. We are now creating the next generation as I mentioned earlier of ETP, for lack of a better name we're calling it ETP version 2.0. So we're doing that to meet the expanding workload challenges. I know some of you had mentioned, you know, it was done in the nasum report during the summary, that you know we need to expand that program and we are on because the workload is expanding and the challenges we're facing in that program. We realize we need to address those we are enhancing communications with the industry as well on that are looking to adopt advanced manufacturing technologies. So you'll hear more about ETP 2.0 later in this workshop. As we are seeing a rapid emergence of advanced manufacturing technologies, it's imperative that the regulatory framework and I've mentioned this before, it's extremely important for us, evolve with this innovation. So with the adaption of new technologies, the FDA faces the challenge of fitting new technologies into existing regulations. That only works so far. We do then need to continue to update and upgrade, if you will, our regulations to handle these new technologies. Nasum has now helped us identify the technologies we can see over the next five to 10 years as I mentioned earlier, and we need a regulatory framework then to provide certainty for stakeholders in terms of how we will regulate those technologies. This framework needs to be flexible enough for these technologies and evolving technologies even beyond the next five to 10 years. Next slide please. So this effort which we called the framework for advanced manufacturing evaluation or frame aims to provide clarity, reduce uncertainty for products manufactured with advanced technologies. So these technologies were prioritizing for this framework are end to end continuous manufacturing, distributed manufacturing, point of care manufacturing and artificial intelligence. So the question is about how we're going to handle artificial intelligence. We're not there yet. We are putting the regulatory framework in place to be able to start handling those areas or those types of advanced manufacturing areas or approaches. So thanks to our emerging technology program, we know that several of these technologies are now far beyond proof of concept, and at a point where the technology is pushing the regulatory framework, we know that and we know we have to deal with it and we are dealing with it. So we've begun by tapping our science and policy experts to help us identify those gaps and pain points in the current regulatory framework so you do that gap analysis, figure out where you want to be where you are, and then what that gap is is what we have to address. So we're embarking on an effort in which we'll be asking for the public's health, sorry, public's help. We do want public feedback. So we're going to be gathering input from the public on our gaps and pain points to further inform our thinking so we're not doing this in isolation. We really do need that input and ask you for your input. When those announcements are made. Once we had an opportunity to understand the issues and leverage both our scientific and policy expertise will begin implementing different components of the regulatory framework. So the crux of our approach will be public white papers, again, they'll be public will be sharing them, identifying the regulatory gaps and pain points, and then released for public comment, that's how we typically do it in the in the FDA. We'll take the public comments post the final versions of those white papers, taking all of the input into account to inform an internal cedar frame roadmap. You'll hear more about the frame, the frame initiative later in the workshop so I don't want to steal the thunder from from that presentation advanced manufacturing is not the only thing of the future. There's also of the present now is the time to develop a framework to keep pace with the innovation. And some people may argue that maybe we're at a pace with that, but we are, you know, our intent is to get catch up if we are behind, and then keep pace with these new innovations. Next slide please. The research program to better understand the science of advanced manufacturing has now fueled nearly 60 research projects that we're doing, including many collaborations with experts in the field, we realize we're not the experts so we do collaborate with those experts. This includes many collaborations with experts that are attending this meeting as a matter of fact are related to many different technologies. The knowledge gained from our research has helped us to, for example, provide guidance for applicants seeking to use new technology such as continuous manufacturing. Our research has directly supported ETP participant feedback, as well as application assessment, which is important. It enabled us to develop the workforce and provide training to support the graduation of continuous direct compression on CDC from the ETP. So this would have not been possible without the foundation of science provided by our research program. So our research really does need to inform the work that we do internally, the guidances that we put together, the assessments that we do. And also, I don't want to lose sight of this and I want the group here to feel comfortable and understand this, that it will also provide us the opportunity to start training our inspectorate. We need to understand these technologies and how to inspect those technologies. So we're taking a holistic and comprehensive approach in terms of what we're doing. Next slide, please. So because they address the recommendations of regulators in Nasim's consensus study report I'd like to close by summarizing FDA's initiatives that support advanced manufacturing. In the first stress that patients with cystic fibrosis HIV, breast cancer, leukemia and asthma are already benefiting from drugs made with advanced technologies. A reason these approvals were possible is the fact that Cedar has long championed advanced manufacturing. Cedar has developed a robust research program to understand the science of advanced manufacturing. In fact, we just awarded five new collaboration products in September of this year. We're currently leading our international regulatory counterparts, the report showed that they wanted, you know, looking for FDA to kind of take the lead and we are around the international collaborations in developing requirements for manufacturers exploring advanced manufacturing technologies like continuous manufacturing. In fact, a Q13 and ICH Q13 guideline and draft guidance are out for comment right now to address continuous manufacturing. Of course our emerging technology program has enabled the FDA approval of finished dosage forms, as well as API's are active pharmaceutical ingredients, biological molecules produced using advanced manufacturing manufacturing. But also that the majority more than 80% of the drugs that are made using advanced manufacturing technologies are produced right here in the US. We also funded the series of workshops at the National Academies that resulted in the published report on form of manufacturing innovations in the pipeline. We're using this innovation to develop and inform our regulatory framework around advanced manufacturing, but to maintain the momentum behind advanced manufacturing in the human drug and biologics programs. Cedar and CBER. So yes, we are collaborating with our CBER counterparts recently established an internal center. We call this the Center for Advancement of Manufacturing Pharmaceuticals and Bio Pharmaceuticals. So we are already partnering with them. The Center then to enhance coordination and collaboration on the science and policy surrounding advanced manufacturing. We need to cover both within our regulatory authorities we want to be as innovative as the new technologies we're preparing to regulate. Next slide please. So then, sorry, I was, I guess I was behind a bit by by one of my slides. If I could have the next slide please 26. So in closing, let us use this workshop as an opportunity continue working together to use innovation to handle an ever changing world. Next slide. So I just want to take this time to thank all of you and to thanks the Mason committee for for inviting me to kind of give you the Cedar perspective and some of our opening remarks. Very good. Thank you, Mike. That was really a marvelous presentation and certainly very exciting to see that the FDA is moving forward and all deliberate speed and responding to to some of the recommendations of the committee and even taking them further than than we were bold enough to advance so thank you for the presentation. We will take questions to Mike. At the conclusion of this session we have two more speakers to introduce to you. And when all three presentations are done we will open up for for questions using Slido and all the other tools. Without, you know, further delay. I'd like to introduce the next speaker. The next speaker is is Dr. Narendra Bram. He is a Senior Vice President of Pharmaceutical Development and Supply at GSK. He has some 25 years experience leading activities in this domain and certainly is is well prepared in the area of advanced manufacturing has degrees in chemical engineering from University Bombay and from Yale University. So, Dr. Baum we're looking forward to your presentation. Thank you Rex. Can you hear me. Yes. Perfect. Thank you to the National Committee for inviting me today to give this talk. Excellent, excellent conference that that you are holding in the next two days and I really expect good things to come out of this. I read the report and it has it has hit all the all the key points that that one needs to advance manufacturing in the pharmaceutical industry. So, if you can go to the next slide GSK has been a leader in continuous manufacturing of small molecules both API and drug product and was a leader in getting those technologies approved with the help of FDA and EMA. But now we are taking the next step and going into the biopharmaceutical manufacturing space and for the last five years we've we've had a program called Advanced Manufacturing Technologies focused specifically on what are the next generation biopharmaceutical manufacturing technologies. And what I want to do today is just give you a glimpse of two or three things that have come out of that program and that are on the cusp of cusp of being industrialized. And then at the end I took the opportunity to just put a slide together on on my experience in the last 18 months what what I have learned living through leading a development and manufacturing organization through the pandemic. So next slide please. So the first technology that I want to give you a glimpse of is what we call agile is the integrated drug substance manufacturing technology that that most companies are developing on their own and some of us. We are also collaborating with Nimble now to come up with with ways to advance this technology as in partnership with other companies. So this is a technology. Next slide please. Which I don't want to go through the benefits of it is it's pretty self obvious but the reduction in the cost of manufacturing the facility footprint the flexibility the increased ability to control our processes. And then the ability to introduce products that rapidly advance through the clinic into the manufacturing settings I think all these combined are offer a one heck of a benefit for for the biopharmaceutical industries. So what we have developed is a end to end continuous manufacturing platform that we call agile. If you go to the next slide. It is based on a perfusion reactor up front and that combines with a continuous downstream process. With with our normal unit operations that for that are required for monoclonal antibodies but these are they are conducted in a continuous way and we can now go from a vial thought from a master cell bank all the way to a final purified drug substance in in one continuous loop. If you go to the next slide. This this is a picture of the overall skid that we have built. This is fully operational now. If you go to the next slide here's another another picture. And we have demonstrated this now at 200 liter scale which is our feed scale for this rig, which is more than enough for producing clinical quantities of antibodies. And we've now applied this to two different active projects that that are in the GSK portfolio and have demonstrated comparability with standard fed batch processes with exquisite control of product quality and the CQA. So this is where we sit with our upstream continuous manufacturing technology. If you go to the next slide. I just want to also give you a highlight of another technology that is coming from our advanced manufacturing technology labs in GSK. And this is one we call Polychiata. This is a technology for a novel sterile drug product manufacturer. If you go to the next slide. One of the things that we we found was the sterile manufacturing has been in a lot of demand and the CMOs are hit or miss. The standards are not usually held up and most of the regulatory issues occur in this in this space. So the challenge that was given to the team was can we create a technology that completely encloses and is a continuous manufacturing setup that will get rid of the need for us to ensure sterility during filling. And the technology essentially is a very simple technology. If you go to the next slide. It is a long continuous manufacturing tube that has a feed at the front end a deep pyrogenation tunnel cooling filling stopping and crimping at the back end. And this is one tube. That is completely enclosed. If you go to the next slide. This has no sensors inside the machine. It has a very small footprint. It is it is by its very nature. It's modular. We can be disassembled and and wash each of these units completely. And the entire machine is completely sterilizable by dry heat. There are no glove ports. This can be put in a completely uncontrolled or at least we are saying a grade C environment without any issues for particle contamination. And we have now demonstrated this unit operating at the normal clinical scale. And we are looking to partner this with with some equipment manufacturer because GSK is not in the business of building building continuous manufacturing rigs. And that's where we sit with this technology. But this is a very exciting technology that can can also be put in the front end of a continuous Lio technology that we are developing in our vaccines organization. So this could become an end to end vial to vial. If we put this at the end of our agile skid, we can have a vial to vial end to end continuous manufacturing setup for biopharmaceuticals as was described by some of the committee members right in the beginning. So that's that's a technology number two. The third technology I wanted to just touch on if you go to the next slide is is the so-called digital twin. Do you have the next slide? We may be carrying another tech issue. Just give us one moment. Sorry. Okay, maybe I can I can just keep going while you catch up with your slides. Digital twin is something that everyone is developing and the benefits are are immense. And ultimately, I think they will be required to go to this industry 4.0 vision that might described in this keynote address. But where we are currently in GSK are we are building the foundations of establishing the digital twins. We have in the biopharm space, we have data driven models that are being developed for the upstream processes with real time multivariate statistical process monitoring for production bioreactors across the clinical and commercial sites. We have these MSBM models in use now and are helping our factories troubleshoot in real time. Raman sensors and other sensors are adding to our product knowledge and process knowledge. And then we are now scaling it out to additional drug substance unit operations like the N minus one bioreactor, the harvest vessel, the mechanistic models in place that can be characterized by first principles like LIO are being developed now. But many of these are empirical models at the moment and not not first principles models. I think where we see the technology going in the future is to connect the building blocks and integrate into advanced process control systems to improve quality safety of our plants. More robust processes move from the monitoring type of an approach to a feedback control and with new sensor technologies that can directly measure CQAs in real time for antibodies, we can actually have a much more direct control of our feed that goes into our reactors. We can predict first design and in silico optimization for our manufacturing processes and then we can also ultimately support the vision of this industry 4.0 that is laid out which is the ultimately lights off manufacture of biopharmaceuticals. If you go to the next slide, I think one or a couple of points that I wanted to make from our efforts with digital twin is that we do need clear guidance for model verification and validation maintenance and life cycle management including post file model optimization and updates. How will the regulators inspect these? What kind of data will be expected? I think there's a lot of ambiguity in the current regulations or lack thereof in terms of how these models are going to be get regulated. And then the second thing I would like to reflect on is that the global regulatory divergence is a real significant barrier. I think this is one of the FASM reports. Most important points that I would like to underscore here is to the extent that FDA has taken the leadership position in enabling and emerging technologies. I think if they can take the next step and extend that leadership to coming up with international regulatory norms and guidance is that all the other regulators are willing to sign up to like the ICHQ 13. I think that would be a big step forward in enabling innovation. Next slide please. So just a few reflections now that are not necessarily innovation or technology related that I want to leave you with, which are that we as an industry I think really stepped up and delivered innovations in a really fast way to enable COVID therapeutics. I would say that this would not have been possible without the FDA's support and guidance along the way. I think we've learned a lot in terms of how much data is actually required and how much data can be supplied post initial submission either during review or post approval. And this is continually a process of refinement that we're going through. I think we got on that journey for oncology products with breakthrough designations, but I think now we have come a long way with COVID therapeutics where the agencies have allowed us to take very smart scientific regulatory risks and provide the data as we go. So I think we need more of that in the innovation space. Easier post launch change mechanisms for enabling site transfers, scale ups. I think we already have mechanisms in place for managing these, but I think for innovations they become a much higher bar. So making it clear in terms of what kind of data expectations and knowledge expectations are there for new technologies will be a big step forward. I think one thing that all of us are struggling with is raw material shortages. And unfortunately we've had to scramble to establish and work with long lead times up to 18 months for some critical raw materials. And that has caused a lot of work on establishing redundant suppliers and alternate sources of raw materials. So how can we establish robustness in our supply chains by allowing alternate raw materials to be qualified and and used in a much more facile way than it is currently done. I think the last thing I would leave you with is the whole travel ban has exposed a key failure mode for our regulatory approval process where the inspectors cannot visit our factories. And I would say that the FDA also played a leadership role in this and worked with our sites to do virtual inspections. But we are finding that each regulatory agency is in a different maturity scale as far as virtual inspections is concerned. So this is something that can benefit from new technologies. If you can go to the next slide, we have a suite of technologies in GSK that we are already using for connecting our operators, doing the training, doing the troubleshooting and these technologies with smart glasses and some other software tools can probably be utilized for regulatory inspection. I'm just putting this out there that is there a way for the regulators to get together and and pick a technology that the industry can get behind and have it standard available across across the board. Next slide please. So all in all I would say that the supply chain agility will be enabled with modular and integrated drug substance and drug product continuous manufacturing technologies. We will reduce cost of goods with process intensification and continuous processes, and we will have an enhanced process understanding and control via digital twin. All these things can only happen with a strong support and enabling regulatory pathways. I think I won't belabor the international regulatory cooperation is essential for us. Otherwise the lowest common denominator always wins and innovation is what loses out. So I think I'll just leave you with the thought that COVID-19 pandemic and the innovation that the industry embraced as well as the regulators enabled should open our eyes to what is possible. And I think we can use that as a blueprint for for establishing new ways of working together. Thank you. Thank you, Dr. Baum really remarkably insightful presentation really appreciate you sharing some of the new technologies and your ideas of how they should move forward. I think in the interest of time we will defer questions and elaborations to the discussion session, which will take place. Once we conclude the next presentation. So without further ado, let me jump directly into introducing the next speaker. The speaker is Jessica Santini. She is senior director of continuous manufacturing business at thermal Fisher scientific where she is responsible for really the growth of the continuous manufacturing business. She has joined thermal Fisher through Paytheon in 2013, which was an acquisition and is her educational background is in in biotechnology both at the BS and MS level so please, Jessica, we're eager to hear your presentation. Yes, thank you for the introduction. Wait. What are slides to come up so I'm just going to see me I'm excited for the opportunity to speak with you all today and representing thermal Fisher scientific, which is a global leader in serving science I thought it might be helpful to spend a second or two describing thermal Fisher scientific to think maybe a less known name from an industry perspective in a forum such as this, but we have over 90,000 employees about 1.4 billion that we invest each year in R&D. One of the things that's critically important is that their official scientific is a broad partner to the pharmaceutical industry find things like instrumentation, single use technologies companion diagnostics, diagnostics themselves reagents specially chemicals and in particular and relevant for today's discussion, a full offering of pharmaceutical manufacturing services so I'm really speaking on behalf of our contract development and manufacturing portion of thermal Fisher scientific. It's also a broad scale of of offerings as well. So also important from a perspective standpoint and that at their office or scientific or a contract developer manufacturer both small and large molecule, as well as the cell and gene therapies and this includes gross drug substance the drug product packaging and logistics so really get involved all on the value chain and the supply chain for pharmaceutical products. If we want to go to slide for please. So I thought today I'm taking a bit of a different approach at that my current role today is all about driving adoption commercialization of continuous manufacturing for oral solid dose. We know we're uniquely positioned right and that we can provide access to this technology for pharma companies of all sizes, and it all stages of development without internal capital investments so we really feel like we're a critical part of the driving adoption of new technologies and so certainly have a perspective on that. I wanted to provide some commentary that's more broad the broad from the thermo Fisher perspective in the broad sense that we have in the supply chain around the particular innovations that were in the report. So if we want to move to the next slide. So this is the post pandemic. Have we changed the criteria that we would use to evaluate what are the technologies we want to accelerate decelerate send our time and energy on as an industry. Right. And I'm not sure that the pandemic has really changed these but it certainly has emphasized them. And so as I look at these technologies and they think about how we as industry would, would think about if these are the right ones or what's missing I think we really have to focus on. Are they going to enable speed, are they going to enable flexibility is it going to be reduction in risk. And some of these comments have been made by earlier speakers and so I think it's an interesting theme that we're finding here. I think I wanted to define each of these because the rest of kind of my commentary really falls into what are these criteria is and how do we think about innovation and farmer manufacturing as it relates to them. And the first one I wanted to define is real speed and the commentary here is not on regulatory approval timelines in fact I did want to take a moment to really commend the FDA for the response and the pandemic and the ability to maintain focus on safety and efficacy, the critical time for industry to be able to respond and we really admire their response from the FDA. Really the con here is on speed, as it relates to speed to clinic or speed to market or overall agility and in particular around farmer manufacturing and the supply chain. We expect and are seeing already that the, the strong response times of the farmer supply chain in the pandemic is really sent a new precedence and standard for our customers meaning pharma companies of all shapes and sizes. And that's technologies that are actually going to be adopted, and they're going to drive the industry forward have to enable speed in some way. So the examples here would be things that would reduce cycle times or process simplifications such as continuous manufacturing that really help eliminate waste from a time perspective in the development during the commercialization cycle for for molecules. Second comment here is on flexibility. And then this here is really I'm defining in terms of scale and geography, and it's really the ability to react to changing market environments, changing market demand supply security and essentially speed. Right so examples here would be how do we create flexibility or maybe platform solutions that allow us to scale into new geographies quickly. Or how do we think about automation and knowledge share that will create flexible flexibility along the supply chain for pharmaceuticals. Last comment here and I think we've heard it already but today is reducing risk, right so this is really related to supply chain but also process reliability. I believe that visibility control redundancy will continue to grow increasingly more important post pandemic. If it wasn't already, which it was. Right and so anything we can do from a technology front that's going to reduce batch to batch variability, improve process reliability are all technologies and be critically important for reducing risk and therefore I think have strong legs to drive from an adoption to a globalization perspective. I think we heard this a little earlier right there's innovations that are focused around great, great science right that they have to drive the business case and they have to drive that to get the adoption that we would like to see within industry and really drive change. So what I did was take a pretty quantitative approach for a qualitative topic, but I wanted to assess the innovations written in the report where would they apply along the various supply chains, and where would they apply against this new criteria in a post pandemic phase. So what's through for us from a thermo Fisher perspective is that accelerating things like process and intensification process control and automation, as well as modular systems, we believe will have significant impact industry along multiple modalities. And these will have a path forward for adoption of commercialization because there is that tangible tangible business impact. That's necessary and that goes back to accelerating timelines, building and flexibility or reducing overall risk. We're going to slide eight. I also spent time thinking about what may be missing here so we as we come out of pandemic like conditions what would would anything change in a five to 10 year horizon with the idea that we want to be staying ahead of the curve here with our efforts. I think there are a couple of categories of technologies or innovations that maybe work time and energy. I think the first we we we just heard about right this idea of traceability of starting materials, certainly a challenge in the pandemic across multiple platforms. Either we improve traceability and therefore reduce supply chain risk for non GMP materials. I think that this is an interesting area to think about some of the technologies that have been deployed in the GMP starting material space or even in finished good tracking. The second we talked a lot about internally was platform technologies and I think this is an interesting one and one that I have conversations on them this daily in my own business for continuous manufacturing for a solid dose right. So this idea of can we standardize platforms within modalities and within starting materials or components that would enable speed, but also enable flexibility and therefore reducing risk right if you think about what you can do to from a data perspective or modeling that also feeds into this but how do we help enable tech transfers or how do we help better with post approval switching of and adopting these new technologies and having a common set of platforms across industry may be a helpful way to do that. Right, so you can see that being deployed and things like continuous or see, but also things like residents and media and more on the biologics or selling gene therapy side of things. So you are around digital and I think about that a lot because I think you know we talked about former 4.0 from a perspective of adding digital into our manufacturing capabilities on the shop floor but also digital becomes more and more important. And we just heard about digital twins so this is the same commentary here but how do we do more from a digital perspective that we're doing more less potentially in lab, or on the manufacturing floor, but also how do we make sure that we're exchanging knowledge at the same time. So I brought this into two. I think the digital piece around modeling we just talked a little about GSK's efforts in digital twin I called that out as a great example here as well. I've had to expand what we're doing maybe even earlier right in silico development and then the in silico modeling for process processes themselves. There's certainly things that are being done today from an advanced process and formulation modeling perspective and I think the more time we spent here that reduces some of the risk or waste earlier in development, better off will be as industry. The last one I get on digital right this is about knowledge share or knowledge management and the idea that to drive adoption and eventual commercialization of innovative technologies we have to come together as consortium or collaboration across academia, academia, industry, industry groups, as well as regulators right. And there has to be that coming together a thought partnership but also this free exchange and knowledge management so that we can continue to progress as industry. I think this has been done well and some of the new technologies that are being pushed through continuous many fresh frozen maybe being a great example here, but along the supply chain and value chain we have to make sure we're doing this. Innovative technologies could be disruptive and have an positive effect at one point in the supply chain but kind of a negative effect down supply chain. So you have to make sure we're being very broad as we work together to advance these innovations. And final slide please. So, I thought it would also take a moment here to talk about our experience with the emerging technologies team or the EP program. We have had experiences of partnering with our customers again from a perspective of continuous manufacturing for all solid dose, but I will comment here right most of our engagement with the with the regular date regulators has been on behalf of customers for a specific product. I feel like these engagements are so very effective very helpful for specific product. As we think about control strategies or overall regulatory strategies, however, I will highlight that I do think that there is opportunity here and this came through in the report of how do we think about more engagement from a platform perspective, so that we can help drive this perception of regulatory risk for adopting new technologies such as a CDC process. I think we applaud and certainly continue to value the guidance that the FDA has has written on things like CDC, the CHQ 13 guidelines these are critical steps for industry. But what we find in our engagement with customers is there is still a lot of perception around regulatory risk here, and we feel like the more that we can bring it into kind of shop floor have discussions around particular technology suites. We will be as a CDMO industry for example to support our customers, but the more comfortable our customers will be with the various technologies that they have access to out in industry. I think this will ultimately help drive adoption and within the driving adoption of an overall system like CDC you're also driving adoption of things like process intensification right advanced process control and automation and things like modular systems and specifically for the continuous manufacturing line. So those be helpful to understand kind of engagement from our perspective. Obviously CDMOs are a little bit in the unique space and that we're not developing our own molecules we're really working on behalf of our customers and in partnership, and therefore our engagement with regulators is always from a product specific standpoint and I feel like this may be an opportunity, especially in driving adoption of these more advanced technologies that I think we can do more as an industry. So with that last slide is just a thank you. I appreciate the opportunity to share some thoughts here this morning. Thank you very much, Jessica that was a really a very concise and focused response and particularly appreciate your assessment of those six technology areas, which are relevant which are not. So, what we're shifting to now is a discussion by the community to the three presentations that we've heard. And again, I would encourage the community to use, you know, the, the Slido tool and, and, and the, you know, the chat as as vehicles for raising questions, but maybe in order to get things started. I'd have a question that either of you can address. I noticed Jessica in your, in your table you had included additive manufacturing, but it did not seem to be an area where you see a lot of accelerated movement could either view address this, you know, where does additive manufacturing fit in the portfolio that either a CDMO or an innovator like GSK might want to engage in their manufacturing portfolio. Yeah, so it's interesting right we recently we've actually spent a good amount of time thinking about this particular technology. And I think it's from a CDMO perspective right we were really driven by where our industry partners going, and what are the things like a GSK thinking about and driving towards because it's important for us to be adopting technologies where there's pipeline of product coming through. And it's interesting that we're still at the point where not quite understanding broadly how are you thinking about things like additive manufacturing certainly there's an an approved product that's that's been pushed through by Apricia and I think it's, it's an interesting to want to watch. And at this point we're kind of taking the stands of we need to figure out how do we collaborate and get in some of this kind of consortia to think about advancing that, and how broadly can we apply that technology right and how many products is that going to help us solve a formulation challenge for, and then how do we scale. And those are some of our key questions still around that particular technology and there's multiple iterations right of how you can do additive manufacturing. But that that's kind of where our thinking is at this point. And Dr bomb, do you have any ideas about additive. You need to hear me. Yes. Yeah, I don't have much to add to Jessica I think that was an excellent summary of where the industry stands with additive manufacturing. We are not at the cusp of taking it. Industrializing it, we are dabbling in it, but it's not showing itself to be an area that that we are focusing on right now. Very good. Thank you. Do we have any questions from the community. Yes, we have a question from Alan O'Connor. And I'll also put it into the chat. He asked for established manufacturing processes. How do you incentivize new advanced manufacturing technologies. Any response from the speakers or from the community at large. This could this could be under the same umbrella as my earlier suggestion of creating a separate breakthrough category for key manufacturing innovations, and maybe giving incentive to the industry to adopt them in existing processes. Otherwise I think it'll be hard to justify capital investment in new technologies unless it. It's a quick payback. In which case, we will go through the process anyway I think for the technologies that are going to require some time to get adopted I think there may be some innovative regulatory mechanism that might incentivize the industry. And in the comments I think we were often faced with what are what's going to be the cause benefit right of doing this and there is a time cost for the additional regulatory approval if you were to say is in my case which for the batch to continuous process. I do see that as a rate limiter and I think that's why we've seen more products come through for continuous OST through development that we have seen commercial switches, very challenging those perceived risks there to the effort that goes in when you you're competing with a process that is the same quality product at the end of the day and so for these many advanced manufacturing technologies where there's a historic if you will, or a standard technology convincing the new it has to come with some some mechanism right to help from a regulatory perspective in addition to be the value benefits of the product itself. Well, if I could, you know, inject another question. Dr bomb you you talked about fill finish and and sterile operation and showed a really remarkable example, which requires, you know, no hands on, at least within that facility certainly the idea of robotics was one that, you know, emerged in and in our discussions earlier workshops, and of course often it is said that the ideal robot is a pump, you just turn it on and material moves. Where do you see the role of robotics, you know, in the industry in general, perhaps outside of, you know, fill finish. Thanks, thanks Rex. I think one of the things I would like to point out is even with the robotic filling sterile technology, the regulations are lagging behind. So some of the annex one regulations that require us to put settle plates to show a particular control etc for environmental monitoring those are by definition not necessary. But we get caught in this regulate regulations required. So how do we get out of that out of that catch 22. And this is something that I would like the regulators to maybe work and enable a update of the regulations for environmental monitoring. When you have a completely closed robotic system for sterile manufacturing. I'll just make that point. Mike, do you have any comment and response to that. Thank you. I was had a bit of a problem here on muting. I mean there's, you know, we, one of the things we're going to do as I mentioned before, you know, we're going to be putting together these white papers we're going to be looking for for public comment public feedback on those things. You know, it's duly noted, you know, I appreciate the feedback. We will take that back and take that into consideration as we continue to move these, you know, different technologies forward and continue to flesh out our regulatory framework. And some of these regulations are European so it's not. It's not under FDS gift to change though so my question is how can the FDA lead in that change. You know, we're working, you know, through q13 you know we're the lead on on that particular on guidance that you know again it's it's been shared publicly so we're looking for comments around that. We do meet routinely with ICH as well as with other international regulatory bodies. And, you know, other, I guess consortium to talk about these kinds of things. But as you can imagine, it's tough enough doing it within the FDA when you start bringing in international regulators. It even becomes a bit more difficult because you're trying to meet the needs of regulatory agencies that may handle things, you know, differently and have different opinions obviously then that we may have. And so that's going to take a while, but but you know it is our intent to be able to. And we are working collaboratively with those groups and seeing how we can move that forward. Thank you. There's another question from Tim. You asked, can you suggest some ways that a high QMM rating might incentivize a company. I think please unmute my yes. Yeah, thank you for some reason it's telling me that I can unmute myself. So, I'll keep the mute button off. You know what we're looking at ways to incentivize the industry one of the things we want to do is to get companies to, you know, give us the opportunity to come in, take a look at their quality systems, and be able to start rating those things so that the public, perhaps, again, we're still trying to figure out our way through this. So I don't know if these ratings or how they'll be shared or exactly whom they will be shared with, because we need to work that out. But, you know, the incentive would be that companies, because there's companies out there right now that there is no way to know which companies are working at a higher level of quality, you know, via their quality management systems. So by grading that or rating those systems, it then gives some of the buyers as well as distributors kind of insight into the quality level of a particular manufacturing firm or company. What that then does is that, you know, the higher the QMM, the thinking is that the more reliable that company would be to continually provide finished materials to that distributor to that, you know, group purchasing organization or wherever they may be, you know, distributing their products to. So it gives them, it gives those individuals some kind of insight into perhaps the continuity of supply that they can depend on. Granted, there may be some additional costs that may be incurred because the company is working at a higher level of quality than others. But again, all that needs to be looked at all that needs to be figured out. But it is to incentivize companies to get to a higher state of quality so that they will have, you know, perhaps less recalls perhaps less drug shortages and provide more continuity into the drug supply chain. I think there's a question for Jessica and the panel. This is from Jeanine and Jean missing regarding CDMO platform technologies. Please. Can we hear some discussion about the opportunities and challenges around the approach. That's a good question. I think one that we wrestle with quite often right in that a CDMO could pick a platform, but unless the rest of industry has picked that same platform right, we can't serve. So, you know, very often even now with traditional manufacturing we're asked for a specific piece of equipment because it's a standard at x company which is a different standard at y company right. So this is why I talk a lot about this knowledge knowledge management knowledge selling their sharing and coming together so that we're together kind of represent these standards, because for a CDMO. We don't have kind of the capital basis to go invest in every variation that a particular company has set up as their platform. We very much have to think about how do we set up platform kind of industry why, or if it's not platform what are the technologies tools that we can apply on top of a particular, you know, piece of equipment with you will that will enable easier tech transfer, and that would eliminate the need for like specific technology sweep, etc. So, it's a tricky space to be in as a CDMO and that we have to really do an assessment of where's most of industry going, and also what works in a multi product environment and those are often not the same. I would be much like to spend time on what could be layer ahead of that right on top of it in terms of modeling work, etc, to enable any specific piece of equipment to do the job. But it is one that I think we have to continue to think about as we advance more and more of these kind of continuous processes added to manufacturing being another where this is going to come up as a challenge for us. I would say that consortia like nimble can play a key role to help industry develop, you know, common platforms around control strategies what are the expectations from a continuous manufacturing setting so I think we are engaging with nimble with that in mind. And I'm hoping that at least for continuous by a farm manufacturing that's going to be a key output that is going to enable the whole industry to agree on standards and and not each each company having their own thing. Wait, this is a question for Dr bomb, given the potential for the continuous sterile processing approach. What would us case interest and will be in broader deployment by Todd P. By broader, if you mean global, I think that is that is a that is an area that we are evaluating right now is can this technology actually open doors for local manufacturing in in areas of the world that don't have sterile manufacturing. It's a very low cost of entry. So we're doing those types of evaluations. But at the same time I said we are not a equipment manufacturer. So we are also looking to partner with with companies that will help us take this technology and industrialize it. Well, just to follow up on that. So you are currently working with with a equipment manufacturer to develop this. So, you know, does that equipment manufacturer need additional incentives to to go outside and market this product. How do you envision that happening. So we have just reached the point of having the prototype built and and and established that it meets the criteria that it was built for. So, who we partner with and how we scale this up for global reach is something that we are just tackling right now. Great. There's, there's a question for that FDA is more general. What has been the FDA is responsive recommendations made by the report any additional feedback from our knob. This is Mike just. I just wanted to read the question again. Well, I mean, the, you know, the whole point, well, first, I appreciate the question. The answer to the question is that, you know, we've taken the feedback that we've gotten and we've internalized that or shared it with the appropriate groups. And based on some of those recommendations, we are, you know, making, you know, the changes that have come across us or that have been shared with us. I want to continue to get that kind of input hence the reason for today's meeting to get involved in more discussion, because sometimes just getting these comments back. It doesn't really provide us always with the opportunity to engage in a discussion and maybe get a little more clarity around some of those recommendations. But as I pointed out, you know, the emerging technology program we're advancing that. We're moving into a second version, which you'll hear about, you know, over the next two days. And that was part of the feedback that we were given as well. Some of the things that we realized is that the comments that were made we were working on internally but we weren't at a point to really openly share where we were in some of that because some of it was in the infancy and in the early years of addressing some of those concerns. One of the reasons for the follow up today is to be able to, you know, share a little more openly with what we've been doing because things have matured since the report, since we got the recommendations from the report. And also it informs us that we do need to do a better job of communicating externally. There are a number of ways for us to do that. One of the ways we had over the last two days, the previous two days, we had the pharmaceutical quality symposium where we talked about a lot of these things that we are doing internally. So we're trying to use whatever avenues we have that are appropriate for us to use to be able to communicate more broadly with the industry to let them know where we are on how we've moved things forward, based on the feedback that we've gotten. We continue to engage like today in a dialogue to try to get additional clarity around some of those recommendations. Thank you. I think Jim Agalako has his hand up for a long time. Yes, I guess I remember a time when the CG MPs came from industry and regulation was adopted by FDA. I'm just thinking that, as we look at innovative technologies are guidance is more of a hindrance than an actual benefit. Should we have more of the what to from FDA unless of the how to I just struggle with that concern question. Well, you know that that concern has been has been going on for for for quite a while. You know, in terms of how we deal with it, you know, we want to get input from the industry itself, but since we regulate the industry. You know, we do have to put out guidance is you know we I can't tell you how many emails I get in the course of the day literally in the course of the day. Well, you know, what is the FDA think about this, you know, can the FDA give us some advice guidance or help. So in order to kind of standardize things across the industry, and also to be able to, you know, hopefully standardize them where applicable and we're appropriate on an international stage. You know, we need to provide guidance to individuals so that they know what the expectations are internally because with that you know within the FDA without those expectations being shared. And typically we do that through guidance, we would receive all sorts of, you know, feedback and we'd start getting into discussions about what's appropriate or what's not so we've got to kind of you know set the goal post, so that individuals are looking for what the expectations are to standardize harmonize and expedite submissions as well as the review of those submissions. There is a question that was posted some time ago on how the FDA is approaching the introduction of artificial intelligence tool and pharma manufacturing processes. I believe you touched on that but perhaps you'd like to elaborate on that. I think some of the other presenters over the course of the workshop will get into that in a little bit more detail. So I don't want to steal their thunder. For what they're going to present and they're probably better positioned than I to maybe get into a little more of the details there, but I can tell you you know in artificial intelligence that's an area that's still evolving within the FDA and how we deal with that. So you know we only have you know a finite number of resources and we need to prioritize you know the areas we're focusing on. And while artificial intelligence is one of those. That's that's an area right now that is not at the highest priority of, you know, our focus our time and attention for those limited resources. We also need, in particular, the industry you know input from the industry to be able to help us and guide us in that area in terms of how that how artificial intelligence is being used and, you know, kind of inform us so that we better understand it because let's face it, you know we're not the experts in artificial intelligence. So, you know we do need to get that input from some of the experts from the experts within both the industry as well as an academia. Very good. Thank you. I guess in the last seven minutes there's a couple more questions one questions from john E. I also posted in the chat. What are the characteristics of FDA bio process research collaborations and the community that have been helpful and unhelpful to the FDA. You know what I will do for the, for the sake of expediency, I will allow that that that question will be answered to some extent. You know, you know as we go through the workshop with the other FDA presenters, they'd be better positioned to help answer that question I don't get involved in that on a day to day basis. So we do have you know Joel Welch is as well as Larry Lee are the ones that have been involved more closely with that so we'll leave it to them, you know, either in their presentation or if the questions brought up again during their panel discussion to provide a little more detail around that. Linda are there other questions that are in the queue. Yes, well, Jeff Barker has four upvotes. If you want to discuss this further. I said a discussion of whether assurance of resilience supply chain site sourcing and technology choices are within the FDA, FDA remit may be in order. And you know, the only thing I can respond to that is that you know, yeah, it may be in order if that's indeed the way the FDA wants to go. Those decisions in terms of the FDA authority are not within my my purview or in my control. So you know I would leave that to you know the powers to be that have more direct influence over that than I know. Also, Tim see asked, are there any impactful technologies that the committee report did not address. Well it's kind of hard for our committee to respond to that so I guess we need to have someone else. You know, contribute. Rex for my for my stamp. Oh, sorry. I'll go ahead. Sorry. From my standpoint I mean what we received you know back in the report is is what we asked for so it met our needs. At that time and again we want to continue to, you know, we want to continue the discussion and the feedback that we got on by you know, here today and then as we continue to present on this area, and as we continue to, you know, publish and have public meetings or at least schedule public meetings, get continued feedback from the industry as well as the public at large. Tim has a comment. Thanks Linda and thanks Mike and Jessica and Norendra for for your remarks really really interesting. I guess with regard to my question about the technologies. Perhaps something we can think about over the course of the this workshop is how for those technologies that we feel will be impactful how we can rally together to enable those specific technologies and what actions we can take collectively to push them forward. And Tim in my eyes that's exactly the reason why we want to have these kinds of discussions so I couldn't you know I applaud you for the for you know for the comment that's exactly what we want to do and exactly what we need to do. It does need to be a collaboration you know there's times where you know I've gotten engaged with discussions, you know with with with sponsors that have submitted applications, and they always want to know what is the FDA thinking you know how's the FDA going to handle you know all of these different things. And the thing is you know we really do want the input we do seek the input from the industry. You know we can't satisfy everybody we can't make everybody happy, you know, you know, I think that's well known. But you know we want to get that input so can better inform our decision making and our path forward. So you know, you know, thank you for that and I couldn't agree with you more. Well, very good. I think we've, you know, we've gone through a fairly exhaustive list of questions. I think according to our schedule here. The, the audience has earned a 10 minute break, and will be reconvening at 1140. And with session to, which will, you know, have a series of presentations, as Mike alluded to first from the FDA, and then from from the community. So, I invite you to enjoy the break, and hopefully come back in 10 minutes to rejoin our discussion. And welcome back everyone I hope you stretch your legs and settled in for this session. So, session two is really about its existing mechanisms to enable innovation. Hopefully you all saw the poll results and slide oh that suggests that the community that's gathered here believes that the innovation that is most likely to have the greatest opportunity to advance pharmaceutical manufacturing is process intensification with a reasonably close second in modeling and digital design. But in this session, I'm going to encourage you again to post thoughts for discussion and questions for the speakers in the Slido poll. I think we had a question in the last session, do you want questions, you know, in a separate tab than the ideas. I think we're monitoring both so don't worry about getting it wrong but I would recommend that the questions for the speakers go in the questions and answers ideas for discussions can be posted in that ideas session if it's not really a question but a discussion theme. So with that, I'd like to talk about the goals of the session this morning. And in this session we will be discussing the existing mechanisms and frameworks that are available to facilitate the deployment of the innovations that have been discussed in the report and were covered in session one. So we're going to focus on examining the respective contributions and linkages of those mechanisms, so that they can work in and how they work to accelerate the implementation of innovation. We're going to try to reserve session three for a discussion of what gaps in those mechanisms exist to lead then through the workshop on how we might address those gaps. So combining questions we asked our speakers to consider our what are the current mechanisms that exist within this innovation ecosystem that contribute to the acceleration of innovation. And through what means are these efforts coordinated or linked to leverage the outcomes. And this really to develop an asset map of existing mechanisms and frameworks that facilitate innovation and pharmaceutical manufacturing, and that landscape view will be used to inform that gaps analysis for the discussion and session three. So with that, I'd like to get us started by introducing Dr Larry Lee and Dr Joel Welch of FDA CBER as our first speakers. Larry is the deputy super office director of science and the Office of Pharmaceutical Quality, as well as the director and chair of the emerging technologies team. Dr Lee's been with the FDA since 2005 he served as a regulatory scientist team lead associate director for science deputy office director and now super deputy super office director. In 2016, Dr Lee was appointed to the senior biomedical research service because of this extensive regulatory and scientific contributions to manufacturing science and complex drug substances and products and emergency, emerging from suitable technologies. Prior to joining the FDA, Dr Lee received as BS in chemical engineering from the University of Virginia with a minor material science and a PhD in chemical engineering from Princeton University. So Dr Joel Welch is the associate director for biosimilar and regulatory strategy in the office of biotechnology products within the Office of Pharmaceutical Quality at CBER, at CDRS, excuse me. He's responsible for assessing emerging complex or precedent setting issues impacting science policies of the office with a particular emphasis on the biosimilar program. In his time at FDA, he's worked as a regulatory project manager, a product quality reviewer and a product quality CMC team leader. He received as BS in chemistry from the University of Kansas and a PhD in bio inorganic chemistry from the University of Iowa. Prior to joining the FDA spent six years in industry supporting late stage analytical development of small molecules. Welcome, Larry and Joel to our virtual podium. Larry, if you can show your camera so we can spotlight you. Sorry for having. Yeah, I'm doing it now. All right, so thank you. Thank you for that warm introduction. It's, it's an honor or privilege to be here today. And on behalf of my co presenter, Dr Larry Lee. We'll be discussing how the emerging technology program works on the future of the program and how we are already addressing many of the recommendations on the nascent reports on innovations and pharmaceutical manufacturing on the horizon. So let's take a step back and ask you know what actually is the emerging technology program. In terms of the what the emerging technology program was established at the end of 2014, and it was designed to promote and facilitate the adoption of innovative approaches to pharmaceutical product design and manufacturing. In terms of the who the team currently has approximately 30 members who represent the office of pharmaceutical quality, the office of compliance and the office of regulatory affairs. We do also invite ad hoc subject matter experts to join with specific knowledge is needed on a certain novel technology. In terms of how they interact, the emerging technology program functions by engaging and collaborating with industry members as they develop novel technologies. The ETP will discuss identify and resolve technical and regulatory issues as the technology is developed and ultimately adopted. This happens from the earliest development stages all the way through an applications regulatory approval. Next slide. In terms of the program objectives, it has multiple objectives that are highlighted on the slot on the slide. This includes serving as a centralized location for external inquiries on novel technologies, providing a forum for engagement and early dialogue with with us to support innovation. Aiding in the consistency continuity and predictability review practice, engaging international regulatory agencies to share learnings and approaches. Identifying evaluating roadblocks relating to existing guidance policy and practice, facilitating knowledge transfer to relevant Cedar and already review and inspection programs, and ultimately helping to establish scientific standards and policy as needed. In terms of accomplishments today, the experience the program has experienced much success over the last several years. This includes an increase the number of proposals received, the number of proposals accepted to work with the program, the number of sponsor meetings, and the number of ETP site visits. Other successes include industry feedback, which gave the program a satisfaction rating of 8.9 out of 10, and ultimately publishing guidance on continuous manufacturing, which was in part based on what we learned in our program. Finally, we have approved 12 regulatory applications that utilize emerging technology, such as reprinting and continuous manufacturing for drug substance and drug product. This includes both small molecules and biologics. Next slide. So with the success, why, why did we identify a need for a change. We highlighted many of the successes. We also noted that there were several challenges for the program as, as it continued to grow. And these included an increased workload that was expected to begin to limit the program's ability to effectively support necessary development of new technology and its industry members. Moreover, industry began to simultaneously request more support from the program. They wanted more dedicated time from ETP members. They wanted mechanisms for CDER to evaluate technologies outside of product approvals, and they wanted more engagement, namely to facilitate innovation. Finally, the team experience turnover as FDA team members left for new opportunities. This had the potential to create gaps in institutional knowledge. We identified this as an opportunity to improve continuity of the program in cases of attrition as well as potentially further improve communication across our work units. Next slide. So what was the solution with all these challenges and opportunities we realized the EPP needed to adapt to its new reality. The program needed to transform itself from an upstart environment into a scaled and more mature model. To accomplish this goal we implemented a three step process to guide ETP to its desired future states. The second step to conduct a thorough state analysis of the program. This included documenting current processes, building out a visual current state operating model. By documenting this current state we were able to identify our pain points and potential inefficiencies. The second step was to create our future state operating model. This new model will support the continued growth of the program and provide standard and scalable processes to support the sustainability of the program for the long term. The final step was to create a roadmap with specific tasks and actions that will move the ETP from its current state to our desired future state. Next slide. The ETP 2.0 roadmap is a detailed actionable document that describes the specific actions, tasks that we will complete in order to achieve the program's future state. Specifically, it highlights not just tasks and actions but also expected level of effort, expertise required, contributors, level of impact and complexity, and potential risk and mitigation tactics. The roadmap prioritizes important areas of emphasis including graduation, knowledge management, governance intake, engagement communication, technology and tools, skills and training, workload management, strategy, and awareness. These priority areas were identified during a holistic evaluation of the program and include particular emphasis on our critical needs, which includes process, graduation, knowledge management including training, and ultimately communication with a variety of stakeholders. Next slide. On this final slide, you can see the timeline towards our program's maturity. It depicts the step beginning with establishment in 2014 through creating the model and our final implementation 2.0. As noted in our progress, we are currently in the process and already implementing ETP 2.0. So with that, I will pause and now invite my co-presenter, Dr. Larry Lee, to present on how the development at ETP 2.0 addresses recommendations in an ASOM report. Thank you, Joe. This is Larry. In the Academy report, there were several recommendations made for FDA and CEDA to consider related to advanced manufacturing and the emerging technology program. I have summarized some of the recommendations here into five major different categories. First, strengthening expertise in innovative technology throughout CEDA. Second, expand the scope and capacity of the emerging technology program. Third, advance innovative mechanisms for evaluating technology outside product approvals, then increase external engagement to facilitate innovation and increase awareness of CEDA readiness to evaluate innovative technology. And finally, expand the leadership role in global regulatory harmonization effort. I will go into more detail on the following slides about how FDA and CEDA are supporting these recommendations from both strategic and tactical perspective. And I also want to emphasize that we really highly appreciate the National Academy of Science to provide this recommendation, make us recognize some of the communication gaps as well as the area we need to improve upon. Next slide, please. With regard to strengthening expertise in innovative technology throughout CEDA, in response to academies recommendations on the left-hand side of this slide, we are currently developing a system approach, the so-called knowledge aim structure assessment system, CASA, for quality assessments which will include emerging technologies or new technologies. So our quality assessors can use such a system to apply a risk and science-based approach consistently to evaluate new technologies so that the industry will know our expectation in a very predictable manner. We have been developing and providing targeted trainings, including utilizing the laboratory within our organization, as well as a partnership with academia to quality assessors and ORA investigators. And we will be working with ORA to train investigators in a larger scale, especially for the technology we start to see in many applications. In order to ensure consistency of FDA inspection of new technology, note that I do want to point out that under the emerging technology program, ETT members already coordinated with ORA investigators to conduct the pre-approval inspection of new technologies such as a continuous manufacturing in some of the facilities. Next slide, please. With regard to advanced innovative mechanisms for evaluating technology outside product approvals, the academies will command the following opportunities. Create new mechanisms and evaluate, expand and consolidate existing pilot programs that allow consideration of innovative technology outside individual product submission. In response to these recommendations, first, I would like to point out that ETP or emerging technology program is not a pilot program. We approve products, not technologies, and FDA will continue to approve application based on the drop products because we all know that we need to account for product specific risk and understand and evaluate interactions between the product characteristic and manufacturing technologies, as well as looking into some of the control strategy elements as well. However, I do want to point out that the emerging technology program already offers a long product specific track that allows feedback on a proposed technology without the need for a sponsor to identify a product or molecule associated with the new technology. So let me just re-emphasize this point. Under the emerging technology program, you can talk about innovative platform technology. Now, because I do want to emphasize this point again because I have presented in many conference about this is the key feature, but it seems like I think there's a communication gap we need to adjust because most of it still seems to me the industry think emerging technology only talking about the product specific technology, which is not correct. Throughout the emerging technology program, OPQ has adopted risk based approach to help streamline implementation of technologies over multiple products using the existing regulatory framework. Let me just give you one example. We have a user suggested using a group submissions to implement a novel container cultural system for multiple products as post-approval changes. Next slide please. With regard to the to expand the scope and capacity of the emerging technology program, the Academy will command the following opportunities for the emerging technology program. Delegate independent funding, increase number of dedicated full-time employees, broaden criteria for entry, increase transparency of the program capacity. In response to this recommendation, FDA thanks to Congress as well as other funding sources. FDA has received funding to support advanced manufacturing, including the emerging technology program. So we do appreciate for those sponsors. And I do also want to emphasize that emerging technology program, even though we have a core member, this program utilize all 1000 employees in OPQ in the Office of Pharmaceutical Quality and select appropriate subject matter experts to evaluate a new technology. And therefore we believe that having dedicated staff could limit the agility of this emerging technology program, especially we anticipate there are wide range of emerging technology we need to deal with in the future. And then this experience, the way we operate in this way because we also had an experience during our PAT initiative, we have a very dedicated group, but we receive a lot of complaints from the industry to say that there's a disconnection between the review staff and the PAT staff. And the criteria for entry into the emerging technology program, I want to emphasize abroad and high level. And it is really up to the sponsors to justify why their proposed technology is novel and has positive impact on product quality, which warrants acceptance into the emerging technology program. We say it up in this way because we want to provide feasibility for the industry to propose the new technology, because if we do have a too prescriptive criteria that may preclude some of the new technology like AI and some other like innovative approach from joining this program. But however, we do recognize that from this, the Academy report, we have communication gap here. So this ETP will increase external communication to educate industry regarding the criteria for acceptance into the program. With regard to the next slide please, with regard to increase external engagement to facilitate innovation and increase awareness of Cedar readiness to evaluate innovative technology in response to Academy's recommendation on the left hand side. First, I want to point out that consortia can apply to the emerging technology program to discuss and get recommendation from OPQ. I also want to emphasize that this is already happening. The thing about this, we will allow them to do it and also as I mentioned before, ETP does not have to discuss the technology associated with particular products. So together you can see that we are already doing it. So I just want to take the opportunity here to clarify this point. As mentioned by Joe, we have a plan under the emerging technology program 2.0 to further enhance communication with external stakeholders to share our learning and exchange information. We are also planning to update our ETP website to make sure to provide the latest update on this program. OPQ already also support the extramural research and training in advanced manufacturing area, as I mentioned before, through a very strong partnership with external stakeholders such as academia like Purdue and Rutgers University. We are currently considering additional opportunities, including further improving knowledge transfer from internal as well as external research to aim quality assessment of new technologies and offering more training opportunities to our assessors and investigators. And next slide please. And finally, with regard to expand the leadership role in global regulatory harmonization efforts. In response to Academy's recommendations on the left hand side, I want to point out several things we have been doing and we will be doing. OPQ already worked on ISH several ISH to develop several guidelines on continuous manufacturing and electrical procedure validation and development and also viral safety of evaluation of biotechnology products. OPQ already shared its learning and expertise in advanced manufacturing with international regulators, such as a PMDA. And I also want to emphasize that we already have a couple of meetings with a PMDA to discuss about what we should do together to advance, for example, the technology like continuous manufacturing. And we actually did plan to reach out with our other regulatory agency like MISA as well as EMA. Unfortunately, at this moment that put on hold because of COVID-19. The reason is that because we do want to travel have a face to face meeting to have a very meaningful discussion with other regulatory agency. So we will definitely continue to do this type of outreach and collaboration. We will continue to work with other regulatory agencies to move toward global regulatory conversion through a variety additional values such as PICS as well as ICMRA in addition to the ISH. So with this, I would like to conclude my presentation. And once again, I really appreciate the Academy to put a lot of effort to put this report together. And I also want to emphasize that this is very in line when we actually plan our program enhancement for emerging technology program and also really help us to identify some of the communication gap. We need to adjust in order to make the industry as well as other external stakeholders to be aware of some of the work we are doing right now. Thank you so much. Thank you, Larry and Joel. I know that the community really appreciates that description of what's happening with ETP 2.0. That's exciting. I would encourage the community to use the Slido to post questions for Larry and Joel and others and to capture some themes for community discussion later. But we're going to hold questions until the end of this, the talks. And so I'd like to at this time introduce our next speaker, who is Rohan Mahathre. Rohan has worked in the pharma biotech industry for the past 30 years, the last 25 of it with with Biogen, where he is senior vice president of product and technology development. His department is responsible for the processing process and product development of all the Biogen products, including associated devices and digital tools. Prior to this role, he's also headed the global engineering and manufacturing science departments. Rohan has also managed the regulatory CMC department and has been involved in the approval of over a dozen products. He has several publications and patents in the area of biopharmaceutical development and analytics. So we welcome Rohan. Thank you very much. And we look forward to your talk. Thank you. Thanks for the invitation to speak. Just a few slides to share. But I just wanted to maybe highlight, you know, things mechanisms for innovation that have worked at Biogen and just my overall experience and just kind of share with you sort of specific examples. And my idea was to really talk about what the outcome has been, and then maybe go back and probably discuss a bit in terms of how we actually got there what were all the tools available and so on. So, you know, so let's start there if you can have the next slide. I think many of you folks have that know Biogen, the company that's been focused in neuroscience for quite some time now and for the foreseeable future as well. And these are disease, you know, fortunately with rather devastating outcomes really isn't anything out there. That's effective enough. And if you can just click one more. And the outcomes here the numbers that you see are rather disheartening in terms of leading cause of disability. Just the number of patients. So seeing all these things I think this sort of, you know, dawned on us, thankfully, number of years ago at this point probably close to 10 years ago just looking at where the portfolio was going. We talked specifically about how we developed our processes in this case the biological processes, and how all that came together. So roughly about, I would say close to 10 years ago. What we were looking at is sort of anticipating how the portfolio is evolving and how do we really stay ahead of what the needs were going to be. At this stage, believe it or not, you know, the platform itself biologics end to end I would say was fairly robust. We had very good success rates in manufacturing and you know the facilities were fully utilized and so on. And I think it's really at that time we said that this in fact is a good time to step up that effort. Really the did the objective was figuring out how do we significantly improve productivity from where we were we are roughly three to four grams per liter at that stage in antibodies and didn't have as much. We had a lot of automation, as many predictive tools and so on so we sort of decided to kind of really take a holistic view and say let's put out what we believe would really sort of change the whole game, and enable us to better serve the patients that we were developing all these drugs for. So we can go to the next slide. I think the key for this. I mean this is sort of existing now organization for a while and something this is not just put up because it's a good thing to show but we've actually really held ourselves accountable for this for both through management, including folks at the plant that it really was was key that innovation had to be the core of everything that we did and by innovation I don't just mean developing technology where it was just the ability to look at how we were doing things and how one could sort of think about constantly sort of keep them back on mind how could you do this differently. How could you bring efficiency in the overall operation. And that's really how we looked at innovation rather than just a fancy tool to be evaluated or some such thing it was really an end to end holistic view of how one could evolve our whole way of working interacting and so on. And for many years, you know, there's something I've appreciated, you know, working at Biogen is that we've enabled this and there's been an expectation really, whether that goes through, you know, the kinds of goals we expect individuals to set, and so on is really really empowering across the board, you know, this is not sort of a top down view in terms of how, you know, things should evolve, but really getting everybody into this and actually measuring this I mean for some years now we have a whole system and I'll talk about that a little bit more. There's a separate office looking at sort of continuous improvement, evaluating all the processes that we have, and trying to sort of figure out and into a large extent looking at investments returns on investments and so on so it's a, it's a fairly sort of involved process and I think on hindsight, thankfully so. And one thing that we've kind of really believed in is if we feel that there is the right science and we feel that that actually is going to help us out. We have been willing to take those risks and really accepting the consequences I don't I don't try to kind of use the word use the term failure because in a way when we are in this particular space. Any kind of learning that comes out of it I look at that as an outcome rather than a failure. So a large part we've we've embarked on several projects over the years, and the outcome hasn't been as expected, but what's been very important is a lot of learning that's come out of it and that's something that has really helped us navigate through where we wanted to go. As I said earlier, the core for innovation here was not necessarily putting out tools, but more importantly to be able to anticipate business needs, and figuring out how one could stay ahead of those business needs so that's, that's really in a nutshell is how we've been evaluating clearly is a, is a, you know, process which one has to look at and figure out how does one, you know, possibly change or, or, you know, bring about certain different approaches. So next slide please. So this is, this is what I wanted to show you, you know, we've been talking I've been talking about at conferences and all for a while on this but this this is really one can call it been the outcome of this particular one aspect of this innovation led us and this is our new manufacturing facility that's up and running in Switzerland, and also most of these tools have been in another facility which is in North Carolina as well these are large scale manufacturing facilities 15 to 18,000 liter reactors and so on. You know. So what what I'm trying to get at here is with the 10 plus years that we have been in the space. We had looked at it truly as an end to end piece where I don't want to go through every every unit operation here, but sort of looking at sort of raw materials, spending a lot of time on initial modeling work and complex raw materials, trying to be able to decipher how changes could impact product quality figuring out real time, you know, supplementation strategies. And as I said, utilizing even some of the predictive models looking at sort of a bulk analysis rather than looking at it and you know in in a more sort of a granular way, and trying to correlate those two product outcomes. And I've talked about this at other conferences before in terms of upstream and downstream controls, where in at least two of these facilities, we have sort of a whole automated loop, looking in within the bioreactor using simple probes like one but looking at a multitude multiple attributes in this particular case what we've shown is glucose could be lactate so on, but being able to figure out when the feeding has to occur based on what the conditions are rather than sort of fixed feeds. And this is all done through control loops feedback loops. And this is something that's been working. Likewise, when you look at downstream. In particular case what we have talked about is control of aggregation, where you're in fact measuring levels of aggregates and changing loading conditions accordingly all this happening real time, something we didn't quite have in our facilities in one could call the previous generation. And likewise using things like refractive index figure out you know concentrations using all kinds of modeling the idea that we've got to hear and which is what we're implementing is understanding what the product looks like at all times. And this is not necessarily by measurements initially it could start with measurements, but then moving into truly predictive models looking at some in some cases maybe random associations to be able to figure out what the product quality looks like. And this is sort of what I want to show you is the outcome and talk a little bit in terms of what tools we had and how we've approached this and other innovation as well as if you can go to the next slide. So there are new way of working that has that has emerged is, you know, as I said, we are going into, you know, previous is really high productivity processes intensifying the culture. And this is just sort of, I'm just showing you what the current stages, we are already looking at what it will be in the next five to seven years. And it could be maybe even four to five four higher than whatever the 10 to 12 grams that we are today. I could easily see it being much much higher than that. It doesn't have to be in the million systems. And since we are we are also ready even as things are settling in into the second stage, looking at what it could be in another five to seven years or so. Something I have strongly believed in and fortunately, sort of many many in the organization is in order to get the kind of control that we're trying to do is we need, we need to have to in order to get the consistent output is to be able to self correct as processes are running. And particularly what I talked about in the upstream is getting to a state where you can have consistent cell growth with the with the understanding of that would lead to consistent product quality. And through all of this, the, the operations have changed there's a lot of localized testing testing happening where it needs to happen. Technology available everywhere simplifying more recipes driven operations and so on. So this is, it's an whole integration of technology processes and people in shift to the next slide please. So this really goes through the mechanism one of the one of the pieces that has been very very effective is the early stage. So what we have is a program called technology investment it's been around for for a long time now. And it's very little money, it's a few million dollars that I have in my budget. And we, every year, we, we have a sort of proposals being presented by anyone, anyone in the organization doesn't even have to be in my group. It's a committee that looks over it. And these can be proposals I'm not something that is needed now but in many cases it could be very blue sky approaches. And, you know, we fund about 2030 projects depending. And these are all short terms fun is just seed money, seed money, either if you want to form academic collaborations if you want to get a postdoc in there, or you want to get interns or co ops or whatever to do some of the work so it frees you to do other things. Many of this funding can go anywhere from a few months to probably up to a year but it's just basic funding for an initial proof of concept doesn't even have to be where everything is sorted out because if something looks promising, we then take it to the next phase where now it becomes more part of our budgets are annual operating plan, and based on the promise we would then then funded. But along the way, I just want to go back where we found it very very effective for all this work is little investment at the early stage has led to a lot of very productive outcomes. And a program against speaking of academia that's also been very helpful as we have sort of a formal PhD program whereby anyone in the organization if they want to pursue a PhD, we will fund that entire thing you know where they will be working on a full salary. But what we do is they will write proposals we would appoint an internal committee member, any one of this, the staff, and then they will work with universities we've had about multiple students go through that, and it doesn't always have to be completely associated with what we are doing at Biogen at that time it could be some forward looking thing it could be maybe some tangential association will be trying to do. But the idea here is we create the time and the facilities, most of the students work at one of our campuses, they will go to universities off and on, depending on whatever arrangements that they have but it's been extremely extremely productive in some years and it's a great sort of a value for people that are going through this. But then going through the next stage, as we start, you know where more of the funding comes in, as things come up, we've engaged several you know speaking at meetings obviously but through, you know, programs at the agency is what we just heard of that has been very productive. And this is really where we then start in some ways, I wouldn't say operationalized but bringing a system to innovation because this is at sort of the myth to late stage, or maybe it's like a phase two of this development is where we have organizations in the company trying to put a business case around it, looking at what the investment is what the outcomes are, trying to sort of figure out, you know, where this would be implemented and what some of the implications would be, and this goes on. And interestingly, you know, even as I showed the previous slide I've been talking about where we want to take a manufacturing which has now been implemented for a couple of years. There was quite a bit of, I mean, you know, there were questions asked like, you know, is the agency going to buy into this, because you're really trying to kind of move things that they may not have seen before. And is it really likely or is it just for a good presentation that you guys are coming to these meetings. And interestingly, at least through my experience and I would like to hear what others may have to say during our discussion. I, through all the innovations that we put together, I actually have had, in my experience, very little resistance from agencies, particularly if the science has been strong. A lot of the anxiety, I feel, has come from within the company or through the industry in terms of what this would mean and you know how could these be perceived but to a large part, when science has been on our side. It's I, I have actually not encountered much resistance at all doesn't mean that there hasn't been discussions or questions, but that's just my opinion here. So you can go to the next slide. And this is what I was talking about earlier, something that we've really been very, very aware of that innovation by itself, you know, can happen randomly. But there have to be pieces come that have to come together one is the overall strategy so clearly, you know, we try to tie where we're going, once we know what the strategy is to a large part we try to also stay ahead of where things are going. The people have to come together and to a large part, where this has helped is management needs to be completely on board to be willing to accept risk. And more importantly, as I said, being willing to accept the consequences, you know, to a point where over the past many years we've actually rewarded and acknowledged the effort irrespective of what the outcomes have been, you know, even the less than ideal outcomes, we have rewarded those efforts. So that's something that that is very important, the people aspect which includes the management as well. Then you also need to have systems, you know, you can't have things getting in the way of progress. And maybe it's the size of our organization or what have you, you try to kind of navigate around that systems technology and processes all coming together. And I think it's really when all these things work is when things start to happen. So next slide. This just gives you, you know, something that we've introduced in our in my apartment. It's called the technology hub, because you know we realized, you know, I mean there's a lot of, a lot of good ideas things moving around, it's very hard to keep track of those things. So it's not necessarily to say that we want to operationalize it but some extent bring some kind of a oversight if one can call it that. So that there's awareness with the multitude of things going on, where things are, you know, what have what the learnings have been. And so it's the idea being that at some point if you park something, we don't sort of restarted go back to square one. You know, bringing a continuous improvement program again which is a formalized program through the entire organization, things like the innovation hub and so on, are important as much as one may think that you know they may be getting in the way of creating too many systems. They do enable in our experience, things to be sort of coordinated better. So that's probably one of my last slides and go to the next one. So just really I just want to end by saying that this is the facility I was talking about our new facility in Switzerland. It's an up and running for the last year or so. And all the things that I talked about have been implemented there and likewise another facility that's been running for a while, using all these for late stage and commercial programs. So I just want to thank a few people, Dan and Aona were on this call today. They've been heading, you know, Dan heading the technology investment investment initiative in us heading up the innovation hub, and large number of people process analytics protein development regulatory manufacturing sciences made this happen. So thank you for your attention and thanks again for this invitation. Looking forward to any questions. Thank you, Rohan. You can hear me now. We appreciated that fascinating view into how by biogen views innovation and values innovation. So I think we're going to hold talks until our community discussion. We'll be following the next talk, which will be by Sarah Arden. Sarah is director of global regulatory affairs at GSK. She serves as well for the discovery and early development of projects in that unit at GSK. She has 15 years of combined experience and regulatory affairs, intellectual property pharmaceutical and vaccines development and research. Dr. Arden previously served at the US FDA as a regulatory reviewer and facility inspector and directed emergence emerging technology research policy and development programs. Prior to joining the FDA Dr Arden founded an AI based technology startup served as a life sciences consultant and IP advisor to startups, law firms and government clients. She received her PhD from Johns Hopkins University and her BS from the University of California San Diego. So look forward to hearing your talk, Sarah. So if you'd like to take the podium. Thank you so much for that kind introduction Kelly and hi everyone. I'm, I've been asked, along with my colleagues Ben Stevens and Jean new primer to present on some of these existing mechanisms as well. And we've put some slides together to go over what we've identified as some currently existing mechanisms that are in use today and provide ways to collaborate early on with regulators and the next slide please. And I mentioned Jean new primer and Ben Stevens and myself put these slides together we're all at glass of Smith climb. Next slide please. In looking for existing mechanisms we identified several different categories that we could parse out the ways in which sponsors firms industry can engage quite early with regulators and other stakeholders. And the first category we identified where these direct sponsor interactions. So the first thing that came to mind, and Larry and Joel gave a really nice presentation earlier on the emerging technology program of course, you know, they, they are the first program that came to mind we have engaged with them ourselves at GSK and in a little bit to that. The next one is seabirds advanced technologies teams the ATT and we've, you know, we've had kind of mixed reviews about about that particular program. The Center for devices also has its innovation group, which is also developing and moving quite rapidly to get to some of that as well to provide other platforms that enable industry and other stakeholders to engage particularly on and have joint learning with the regulator as well. So other national regulatory agencies, the MAs innovation task force, the UK's MHRA and Japan's PMD all have their own innovation offices that enable early engagement for sponsors. Next slide please. In this category we identified where these guidance is. And these, these are interesting because they provide some thought leadership that comes together by dealing with what knowing what the agency is dealing with industry and what are some of the pain points that industry is having in areas that they want to move forward in. And so some of these guidances that have come out recently are the PT guidance, the continuous manufacturing guidance which came out before Q 13 the ICH community had just recently put the Q 13 and of course the advancement of emerging tech application which is kind of the backbone of the ETT Q 12 and then divide additive manufacturing for medical devices so all these guidances are providing this framework that industry can certainly go to when they are at a crossroads and trying to determine how best to move forward, but they are just, you know, information that's provided it's one directional. So it doesn't provide that engagement but at least there's a framework to work from next slide please. The next category we identified with these innovation initiatives. And, you know, particularly the FDA, there are a number of initiatives that exist. They may not all be well publicized but they nonetheless are ways that the public and stakeholders can engage quite early and have a say in the direction of how and how the regulator, the regulator can innovate its own regulatory policy. As well as how the industry can move forward in terms of their innovation and commercial strategy. Some examples of these are using the documents that CD CDR and CDRH are using for public comment here's an example in the federal register for quality management maturity which you might spoke about earlier. And so these provide this opportunity for public to engage early on and comment. There are also initiatives such as this one right this is a platform that is a really nice platform that brings various stakeholders together academia industry regulatory and the Duke Margolis Center for health policies another one such platform. Recently, for instance the FDA had one workshop there on establishing high quality real world data ecosystems. And these are really nice meetings because there there's a really kind of mutual discussion and hopefully some ideation that can happen that these venues. Another interesting one is really looking at within the agency, different various offices have their own annual reports they publish annually. This is an example of one annual report there's also other reports that are published regularly. And, you know, going through these you can identify some of the initiatives that are being developed yet to come, and also observe and monitor some of those that have already been in place and see where the, how they're impacting industry and innovation. And there's also an interesting initiative coming out of the digital health center of excellence, which is actually part of CDRH Center for devices so this is the center of excellence that was recently organized and launched as a platform that enables all stakeholders to kind of come in and interact with the center. And as it's, it's, you know, you know exactly where you need to go if you have some particular questions. And the process allows both the agency as well as the stakeholders to grow, learn together and really allow the community to move forward. Next slide please. Another area we identified are these FDA external funding opportunities that exist. These are in the form of contracts and grants CDRH has its own BA and grant opportunities so to see her and throughout the agency there it's not at the level of course of NIH, but you know the funds that exist for funding and supporting new technology development. Here we have a certain priority areas that we've looked at such as supporting new approaches to improve product manufacturing quality. And then the other priority area ensuring FDA readiness to evaluate emerging technologies. These are some examples of where funding goes. CBER CBER had an RFA out recently for enhancing innovations and advance manufacturing technologies for vaccines against influenza and emerging infectious diseases is another interesting area. So these provide an opportunity where oftentimes academia comes in and submits a proposal, the agency reviews those proposals and determines how best to distribute funds and also meet some of the mutual learning goals that can advance both regulatory reviews side policy side as well as of course the commercial side and just generally moving innovation forward. Next slide please. And lastly we we also look to public private partnerships. You know these are great platforms where multiple stakeholders that are at the forefront of innovation can be engaged in discussions together. The MEP National Network, NIMBL, BioFab, BioMaid and the Medical Device Innovation Consortium come to mind of course manufacturing USA as well. And NIST is of course it's another sort of it's an agency that can provide a role as an independent party when different industry members need to meet and discuss a particular topic and move that particular area forward. So NIST is also engaged in a lot of that. And next slide please. So, I want to speak a little bit to the recent experience that GSK has had with ETT. Some of this was discussed earlier. This is a high level overview. And we did find that the engaging with ETT was really useful pathway to integrating the novel manufacturing and testing platforms that we presented. We submitted a meeting request to discuss the novel microbiological testing platforms with ETT. We had discussions that were centered on leveraging prior knowledge for method validation approaches for product specific method validation and verification following method transfer, sample prep and bracketing of the evaluated species and comparability to compendial methods. In the process, subject matter experts from the different FDA divisions were assembled into the meeting package review, which is also really unique way to engage very early with the agency, and get the multi discipline perspective and identifying those early risks that can impact how you are going to move forward in terms of your go to market strategy. So prior to getting to that IND stage so we found this to be very useful. The feedback was robust and the agency provided us with actionable responses and encouraged us to seek additional interaction as we continue to develop the technology with that feedback that they had given us in mind. Next slide please. So here, you know we sat down and we thought about well what works, and you know what can be improved or enhanced to maybe make things a little bit easier and more efficient for the community and all stakeholders. And the first, going back to that first category of sponsor direct sponsor interactions. We looked at those centers and the different mechanisms that are in place for engaging early with industry. You know, one of the areas that we thought could be an area to look at to improve is the consistency across the centers and maybe using something like a pre pre IND sort of situation type C process that could enable all the centers to have a similar approach, depending on the product type that the sponsor is working on. For instance, some of the, some of the, I guess, mixed reviews that have come in about the Ctt or that those informal interactions with them may not. That's presenting a new technology and that's one area is that consistency. Another is really having a somebody who is a well publicized clear champion point of contact, or an office that has that is directly associated within the centers to facilitate sponsoring our actions we thought that that could also be beneficial to to the industry. And another thing that has come up and I think this has come up in the past as well is kind of considering a technology master file. You know, is that something that could be considered as a mechanism that we can review the technology in the absence of an application cross referencing and this is something that potentially manufacturing equipment vendors they might be able to do something of this sort. Those are the three areas we thought about for opportunities to to improve on the sponsor interactions. The next area is global alignment. And not there yet. Global alignment. So that, you know, we thought just like the consistency across centers. I think that would be really helpful to have more global alignment and one of the barriers to and concerns I think many industry members feel with innovation is, if we take something to one agency versus another it's going to have with the different different perspectives different risk assessments on how we approach the bringing something to market what is the commercial strategy going to look like and it's not consistent across the board. We're having, you know, MOUs between the agency and counterpart innovation task forces at other national regulatory authorities that enable parallel scientific advice consultations for example to achieve more alignment on regulatory risk and and and particular technology we think that could be very useful. And we've just recently seen something like that come out of the Center for devices just this week, where they jointly published a best practices for machine learning in digital health with the UK's MHRA and Health Canada. So we know that there's precedent for that and that could certainly facilitate some of the concerns with bringing something to market across different regions. And then lastly we have innovation centers and test beds. So the agency does support academia and maybe some smaller companies that come in through the form of those contracts and grants, but we really were, you know, questioning how impactful some of these contracts and grants are when it comes to commercializing a new technology and how does that impact really the private sector so something to think about there. And then lastly here, the agency can also consider more collaboration with private sector R&D that's in that pre competitive space with craters or using test beds. These are already in place in some cases but it's not something that's widely done or really publicized. So that covers some of the areas that my colleagues and I had come up with that, you know, could potentially improve what's currently out there and make things more efficient for the community. And with that, I would like to thank you all. The next slide is the last slide and I'm happy to take questions and engage in the follow up discussions. Thank you Sarah that was really helpful and I, it was a terrific summary of all the different mechanisms, you know that that you can see from your perspective. So with that, I would like to invite the speakers from Penn and Joel and Larry to join us in the spotlighted part of the discussion and I would also like to encourage all the participants in the workshop to use the Slido function to pose questions or ideas for discussion in this thread. So, one of the things, you know, to start us off, one of the observations that I've had that I think is, you know, Larry mentioned the communication problem right there's so much going on, and it's difficult for external stakeholders to have insight into all those different mechanisms what is currently being done. And so, I would suspect that part of that challenge is that when you hear, you know, when you consider from Sarah's perspective as preventive presented and that everyone have presented about all of the different mechanisms that are on the table. It seems that often FDA defaults are cedar defaults to the ETT right as the mechanism. And while that's certainly an important daykeeper for it. Well, I don't want to use the word daykeeper enabler right and it's a very important program, it is not the only program that is there and shouldn't be the only one that should be considered I would imagine at this stage in the game, even though that might be the intention to grow that program to sort of be the all encompassing face of cedar for innovation. I just wondered if the community would like to react to that if any of you would like to share your perspectives on sort of the sufficiency of the FDA because it does appear that it's very much of the ETT, excuse me. It does appear that it's a very appreciated mechanism, but is it a sufficient mechanism, and I recognize that I'm bleeding over into session three. So, just just a flavor of that. And I'm happy to start. So, you know, default into ETT you know I think part of part of what we've had success in the past and part of what we're continuing to build is, you know, robust, not just engagement processes for intake and that's something you know we highlighted in our presentation and I think a lot of the implications that rejected it's because it's not quite a right fit for ETT so I feel like a lot of a lot of the important logistical things that happen on the back end is really finding those things the right home so I guess I would push back on the idea that we're, we're defaulting to ETT I think we're really being thoughtful about what's included and we're where there's an interesting development program that ETT is not the right fit for for a variety of reasons trying to steer it in the right direction. I think so I think when ETT establish is really to give people about the clear point of contact if you do want to develop technology for future regulatory submission right. So, I think we really need to think about, like this is the scope of that program, because like in the past like people have no idea where to go. So, so but I agree with you, with you that I think it depends on the purpose like what type of innovation you want to communicate, but the purpose of the way of you want to communicate with the agency. Other other platform maybe is a suitable like let's say if you do want to advance regulatory science, then like you start going, this will not be go will not go to ETT we have the BAA and also grant processes I think Sarah actually did a very nice job to organize to do a lot of stuff and then also I think at Adams and Tom will actually also talk a little bit more about the regulatory framework and also regulatory science. So they will actually also let you know like how do we communicate those because I already mentioned we want your input on the regulatory framework part. So, so far. Thank you. I think we have one question that I believe you can quickly clarify. Is the emerging technologies team ETT part of the emergency emerging technology program or is this a separate team and FDA so I know Larry Joel would like to just clear up any confusion on that point. Yeah, I can clarify that Joe please. Yeah, I guess it's my apology. I think they are the same thing. I think we have emerging technology program but mainly is driven by the emerging technology team. As I mentioned before, like this team is the core team but we can have an ability to recruit any subject matter expert within the OPQ, as well as outside OPQ, depending on the nature of the new technologies. Yeah, no I think we sometimes use the terms of that interchangeably but it's it's really the difference between the individuals who are the team and then kind of the thematic program which is you know the entity to himself but obviously there's there's a lot of overlap there between the two. So, we have one question in the slido that I think it's more more general, but I suppose this, this community, or the speakers could respond to this what's the primary part of the process that by manufacturers would like to see more innovation introduced and why. So, that perspective on where it would be most useful to see an innovation appear, I suppose. So you're asking what area is that right. I believe that's what the question is asking. Yeah, I mean it's, it's necessarily it's hard to generalize it also depends on where your current platforms are where your network is and so on, I mean manufacturing network. I mean, I mean you saw from the poll I mean there is a good amount of effort on improving you know intensification improving productivity and so on. And this is where things like continuous come in because the other idea being is how long do you want to build larger and larger facilities, you know so many of these ways in which you can optimize that. I think there's, you know sciences and advanced enough, where we can start thinking beyond just the traditional choke platforms and so on so I feel that's where it is. But the other piece I do think I mean at least in our organization we believe that, whether you call that digital or what have you is really around process predictability. Because there's just so much advance been made there. You know whether that be through predictive modeling and so on. But I do think that that has very, very big value, because if you're producing at the rate at which we are, and at the productivity that we are a batch going down is is a large expense and you know without all these predictive tools, you could have many batches go down the drain before you actually assess it. Yeah, if I could add to that I would second, certainly what Rohan said. You know I think some of the considerations that of course they're related to do risking earlier. You know if that's related to applying models, and I think the agency has recently been more endorsing of using models earlier on. So apply those models early so that you can reduce time, you know, or fail early, the risk stepwise. I think that that's an area of course process intensification is related to that because you know you. There are specific areas that could be more streamlined and then in consideration of that are also, you know how ai plays into this how digitization of processes and systems that can become that are that are mature enough to handle data rich, you know, process technologies and understanding how the data is handled versus just collecting all of it. And, you know, putting together systems and mechanisms in which you know exactly how that data can become meaningful and useful for your process to apply it towards process intensification or de risking and also being able to skill much earlier without all that risk so those are clearly high priority. Thank you Sarah. So I'd like to loop back to a question I believe it was john Erickson that asked and I'd like to invite john if he's willing to come and elaborate on that it was effectively what are the characteristics of successful FDA collaborations with external partners. And believe it was that question was posed in the Slido during my conscious talk. And he suggested it would be good to punt it into this, this discussion. So, let's see, if it was john Erickson who posed the question I'd like to invite john, or really any in the community who'd like to raise their hands and give a perspective on that but first I'd like to ask our speakers for their perspective on that. So you think external program that has been successful with the agency that I I think it's more if you, if you view one mechanism for fostering innovation as an external collaboration of what are the elements that make that collaboration successful. You might say that he will pun the question to Joe or to me. I think it was both of you. Okay. Joe why don't you go first. I mean, it's kind of a hard question right what makes what makes it successful so I think, you know, and I think you know Tom and Adam will I think speak a little bit to these kind of concepts to later and later in the program. I think, you know, there are a variety of processes and I think Sarah did a nice job highlighting that so I think, you know, it's hard to hard to generalize what makes one successful I think certainly having having the processes we do that that try to identify up front what what success factors, you know should be considered and making making sure we're making informed decisions where we make investments I think I think the process itself is part of what drives that success. And you know, I think, sometimes these product projects you know there's always uncertainty about you know where the industry is going so I don't know that I'm able to generalize much more than that. Larry do you have any thoughts it's kind of a challenging but interesting question. I do have some thought to that based on the interaction we have with industry, many experience. I think the key for the successful collaboration is really be direct, be honest and be transparent. I think this to me will be a key success factor because so far I think the program we have is successful in a way that because I think there's a lot of contribution I have to acknowledge a lot of contribution from industry because they came in. They came here, the result with us right and, and really transparent because like remember FDA is not the one who do a product development right so sometimes I have to say that's like, we can only make a good decision, or we space decision based on the information provided by the industry or by the manufacturers. I think be really transparent. And then also from our end I think Joe, like, and I always try to make sure that if we disagree with you or we agree with you with you we give a very clear reasons. And then we do so not just like call the regulation, because of regulation we cannot do this, we try to be scientific and risk based. So I think those are really important factor is based on my experience. And then if I could add something I think from from the industry side I think it's really helpful to know what kind of questions you need you want to get answers for from the agency. I think that you're asking the right questions, and that you have. If you do have some supportive data to kind of go in with those questions, or if it's early in concept you still have some kinds of questions that the agency can really provide feedback for. That's, that's very helpful. Sarah, anyone in the community who would like to join this row and I forgot to give you an opportunity to answer that question. I mean, I think I agree with what everyone has said, you know in this particular instance what I showed you are manufacturing, whatever the reframing. One of the most discussions is that when we were proposing new things we weren't saying we'll do this. As a result of this we won't do that. You know and I think that's sort of where a lot of sort of maybe one debate or friction has come in the past where proposals go forth, say that you know if we do this this is what we don't want to do. And many times when it comes to control strategy changes from the norm is when issues come up. This isn't much of the technologies not like that we would just want to keep doing everything. But the way we had approached it was that we want to do this to get a better outcome of a process and a product, and just left it there, and that actually enabled for a much better engagement. We have another question from Tim Charlewa in the Slido and Tim's question is, could consortia bring forward non proprietary archetype products with detailed data sets to collectively de-risk technology and I think that's for you and the emerging technologies program and team Larry and Joel. Larry would you like to start or should I I think Larry highlighted you know that there are different tracks for engagements in his talk and I think you know there is there is the possibility of having I think engagement on, you know, if not a specific product at least some data to have some meaningful back and forth in terms of providing some specific feedback I think one challenge anytime you move outside of having a specific program a specific molecule, a specific set of questions a specific use case, you know, the questions become more general but then the feedback has to become more general to and there's that's just scientific reality so I do think there are places where we can engage in a different way on this you know obviously it still needs to have enough meet there for I think discussion, but I think you know there are there are different groups that we have engaged in this pathway as Larry mentioned so I think you know that's that's certainly a tool but again it's it's still going to be I think driven based on you know the type of engagements and questions we need to discuss and also how much data and how much specificity we can bring to the conversation. Yeah, I think I agree with Joe. I think we definitely have no problem to entertain this type of a meeting terms, even under emerging technology. Right, but Joey is correct. Right, a certain point. I think we can talk a little bit share my experience with you. We have a lot of this type of a discussion already, right. Very productive. I mean, like some of these are very, very early technology development. And, but we give a high level feedback and also like the company did a very good job to provide high level background information. Right, but I do want to point out that some of the specific like you really cannot assess the risk until you identify certain product and molecule due to the interaction with the specific technology like for example I can give you the direct compression continuous manufacturing process, your high dose drug low and low dose drug low the risk would be very different. So if we talk about the technology platform is very difficult to get into those area. So I just want to solve a share this to point out some of the limit quotation, we may have, but if you start to suggest some like in the things can still provide information about certain product characteristics not naming the product but certain product characteristics you are interested using this type of a technology I think that will also help help where we helpful to but I think in the emerging technology program. That's a lot of facility really depends on what type of feedback you want from from the from the agency. Thank you for that Larry and Joel, any, anyone else and again I'd like to make sure that anyone in the community that would like to contribute to the discussion knows that they are welcome to do so they just need to raise their hand or enter through the slide or chat or the ideas in the slide or chat, so that we know to call on you and and highlight that idea. And to see if anything, if anyone raises their hands, we had another question for Rohan in the chat from Tim Charlebaugh. And that was a question as to whether your phases of innovation that you showed on your slide a track with clinical development of a product, or are they also applicable to introduction of technology for approved products. Tim, where have you been haven't seen you in a while. But no. So, when it's associated with a product, right, I mean, if we time it we do time it with the clinical which is the idea being that whatever new technology or platforms we put in to make sure that product for pivotal trials is made accordingly. But there are a number of cases where in fact we've used it for commercial products, including a, you know, including some of the modeling work that I've shown me and we've, we've used it for a product that's been in the market, what about seven years or so. Thank you. And we have just a minute, a few minutes left before we go to lunch, and I don't want to slow us down but I thought Sally answered asked a really important question. And so I'd like to ask Sally. If you'd like to to pose the question yourself or bring that up for discussion. I think I'm sorry if you can be on camera and we can spotlight you. It's also wonderful. Can you guys hear me right. Okay, awesome. Yeah, so I, it's just a general question. And I think that, you know, sometimes, um, you know, there are changes and when we talk about certain things and we because we think that we understand them then we don't take enough time to really digest and harmonize the point that everybody's going to be aligned with what we are really intending to do. So this is, this is again goes back to change management. My question is, you know, I have I have worked with multiple filings and we talk about science based and risk based. Um, but in particular, I, you know, I think that people understand a little bit more about what risk based means. But I have seen in multiple occasions when when folks talk about science based. You know, many occasions I have seen folks talking about just the data right if you do an analysis and well I calculate a p value for that or I calculate some sort of like statistics on that and they assume that is because it's the science of statistics is science based. So, and then I haven't seen in other cases where people try to use you know like the understandings of the process itself and the engineering and concepts of mass balance and just fundamentals of the process to define what science based is. So, I might be not I don't know if it's completely out there I have seen it in multiple guidances that we talk about science based. I just don't know if folks are still if we have made some sort of agreement of how we're defining science based for people. That's more towards the folks from the FDA because I think that I think that there's I have seen that gap and and I have seen that gap trying to put a filing myself working with other colleagues are helping out. Yeah, I can address this question first and then Joe to me a little bit. I think in terms of you are talking about the consistency in the post approval, even like let's say the evaluation right. Yeah, I agree sometimes like, like, I just want to let you know the amount of work we are dealing with is more than like, a supplement per year as well as, as well as even for the original is the number I don't really remember the number. Right. I think a certain type of inconsistency I think definitely from from our, from our end is expected. And I process also considering that we have quite a lot of large pool of quality assessor, some of them are with a little bit background those also can may contribute this as well. But we do actually tried our best to ensure consistency apply the risk and science based approach in our assessment. So what we are doing like, like we, I'm not saying that we finish in this area. But what we are doing is that we start to, we have already incorporate more like a team based approach based on different discipline to evaluate those type of application. So really the science based approach. And then to your point Sally, I think some of the things is that even though for the individual, they may have a different type of risk assessment framework they use vary from one reviewer to the other reviewer. As I mentioned in my talk little bit about the program like the castle program we are going to develop and basically really to develop more formalized with base algorithm using the latest scientists and then this system is going to be maintained and continues to improve based on the best practice we have here is not, it's not there yet is still in the development and initial implementation but that's where we try to get to that will actually help us to improve our consistency in the near future. But Joe also is the person who developed this type of system for biology so he may be able to give you a little bit more granular level information. Yeah, I think, I think a lot of this always, you know, turns back to communication and we have you know training really, you know, good, good understanding of what we're talking about but I think all the tools that we're developing I think aren't necessarily either even technology specific but really are at the core trying to address this this communication and this back and forth, you know, challenge I would throw besides costs you know PQC MC and how we think about information being submitted I would throw in, you know q 12 where we talked about trying to identify, you know concepts data expectations shared understanding of risk up front. But I think all this is, is driving towards a better shared understanding of that and you know the idea of what's new data what's existing understanding right the definition of prior knowledge we've all agreed on for a long time and I CH as it is so I think all those, all those tools are our neighbors for us to continue to move forward in terms of sharing this vocabulary. Thank you. It is time for lunch break, but Sally, yes, do you have one more question. Yeah, very quick. I, you know, just, I just wanted to say thank you to, you know, both gentlemen for answering that to that question now. One thing that I would like to add is, you know, like sometimes we think about this consortium that we tend to work with and there's other groups that are, you know, apart from the regulatory as in like sharing data and doing things that are very ambitious right, I think that I have found that some of these consortiums are very effective just sitting down and having everybody in the room and just saying hey this is what we're going to be agreeing to, to call this one moving forward like what we did with the APC workshop right. So I think that that's, you know, one recommendation that I can give that I don't know if I, you know, the committee gave it during our document is, you know, using this consortium just to find alignment with regards to some of the new terminology that it's coming, because we're going to be able that we're going to be enable enabling folks to share best practices way better if we align with the same, you know, concepts at least. So just just was thinking about that while you guys were talking thank you so much. Thank you Sally for the, for the suggestion. And thank you. Now, the only thing we have left for lunch is to say thanks again to our speaker Sarah Joel Larry and Rohan, you know, for the time and the thoughtfulness that you put into your presentations I think it'll set us up really well for our next session on where the gaps and and opportunities live in building these mechanisms. So thank you all very much I think Linda wants us back at 145. Thanks, thanks everyone welcome back from lunch and welcome to session three. Linda, do you want to display the results for a minute. Yes, we are going to pull that up in a bit. I think there's some interesting poll questions there will just let people look at them are we able to see these I look back and find out and it's, I couldn't I could see that I have responded but I couldn't see the results in the, in the video app so I just wondering if people had, were able other than when we display them on the screen, if they'll be able to see them. It's just on the main screen here. Everyone else has a participant participants. Yeah. Okay so this is probably the right time to quickly look at and reflect on these poll questions and thanks to folks that have responded. These are just to stimulate a little bit of thought and I think we can certainly come back to this and the community discussion at the end of this session as well as in the other sessions. This question about the extent that changes in regulatory policy procedures practices or culture could could affect innovation and pharmaceutical manufacturing as you see some extent. Or to a large extent. So that's still still, you know, some some opportunity, you know, at least reflected by the community there, moving on to number six, which, which sort of focuses on the how part of that question and it's kind of split regulations review practices, workforce training and and guidance with emphasis you know a little bit higher on the on the last two. Thanks for those responses. Number seven moves over to industry practices and here there's even larger louder voice I think to a large extent innovation can be enabled by practices and industry. I think that's kind of a strong vote there. I think in that direction which not surprising based on the conversations we've had earlier, and looking on to number eight. Greater greater this was sort of split vote but greater willingness to accept risk, not at all shocking based on what you know the perceptions of the pharmaceutical industry are. I think seeing increased pre competitive collaboration to substantially do risk implementation, and you know something that I think certainly been enhanced and accelerated by the pandemic increased recognition of manufacturing as a value driver, and also, you know a lot of votes for for greater transparency regarding innovation activities, which is something maybe we can come back to talk about. At the end of our questions area we have one more. Okay, great thank you. Some extent academic practices could also enhance and is that the end there Linda. Yes. Yes, thank you for that so thanks to folks for responding and this is to get people thinking and we're hoping to stimulate some discussion there so welcome to to session three, and I just wanted to take a second. I would like to thank all of the speakers and participants in sessions one and two this morning I thought it was thought provoking and and very useful those sessions. I appreciate the engagement and for those that are hanging in with us for this afternoon. I really look forward to continuing and enhancing that discussion and on into tomorrow and so as we look at the overall flow of the agenda. That's kind of a pivot point in the agenda so this morning. We wanted to have the opportunity to basically disseminate awareness of the report itself, and to talk about reflect on the technologies that were emphasized in the report, as being those that are impactful in the near future, and then to reflect on the existing mechanisms for accelerating and enhancing and enabling manufacturing innovation, and to give FDA a chance to give visibility to what they're doing, which was very, very useful. And at this point we wanted to pivot a bit toward what gaps do we see this is Kelly mentioned this earlier what gaps. Do we see in the community as a whole for enabling innovation and that's what this session is intended to be and as we move toward the flow we're trying to use this session and the discussion to say well these are the real problems in front of us. You know, as it relates to the hurdles that we face and really hear from people the report did weigh in on this affair amount but we want to hear from the community and draw energy out of that. And, and, and then, as we move through into tomorrow's agenda will be talking about solutions that should address these gaps, and then the path forward so I really urge you to continue to stay with us and participate because as I mentioned earlier this morning. So we're really looking for community engagement and ownership over this problem statement and very much appreciate your, your attention to this workshop and ongoing attention to the issues that we face as a community. And at the introduction to this session specifically we have a series of four short talks, you see on the screen. These are intended to be approximately 10 minute short talks, and they're there to provide some opportunity for additional reflection on the topic of what gaps challenges communities do we see in enhancing and advancing innovation. And, and also to use these talks as a springboard to stimulate the discussion. So we will have the four 10 minute talks serially I'll introduce them in turn. And then we will hold questions until the community discussion at the end. I think we have 45 minutes for that at the end which will. Please continue to use slide out to input your questions to speakers and your ideas for discussion. I use the upvoting feature for that. And, you know, remember, you know, raise your hand if you want to speak as well and we'll try to recognize that and the extent possible we're going to try to get voices in out here and really hear from people and try to stimulate some discussion. So, with with that as an intro and I hope I haven't forgotten any of the ground rules there. First, our first speaker is Tom ran so off, who is is co head of the biological franchise at resilience of manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption. Tom. Thanks Tim. Can you hear me can everybody hear me. Great. Okay, well, I think we can advance the next slide I'd like to just start by saying it's it's a real pleasure for me to be here I really enjoyed this discussion and, and I really appreciate the opportunity to provide just some brief thoughts on some of the challenges related to new technology adoption and in our industry. And because we're all products of our experience. And this is, you know, my own perspective I wanted to, you know, start by sharing, you know, my my experience and so you can, you know, then judge the relevance of my comments. I don't have any comments on that but my my career has been primarily focused in the recombinant protein and monoclonal antibody field. You know, over 30 years in bioprocessing and, and I have worked on a number of new technologies that have, you know, been successfully introduced at some level to the industry. So, you know, the bioprocessing processing area, and, and obviously, all focused on bioprocessor bio pharmaceutical manufacturing. And I'll start by dating myself by acknowledging that one of the first new technologies I worked on which is now obviously considered a conventional accepted technology is protein a, but at one point, when I entered the industry in the in the mid 80s. Conventional accepted approaches for purifying proteins from complex mixtures were primarily ion exchange chromatography and precipitation. And the idea of using a coat protein from a pathogenic organism as an affinity like and to purify a therapeutic injectable was viewed by some as a radical and risky new technology but obviously now we'll you know know and appreciate the value of affinity technologies and I was involved in some of the early evaluation of protein a and antibody processes and later in the development of recombinant forms of protein a and obviously that field has continued to evolve. As we now have, you know, base stable protein a like ligands that have been successfully adopted by industry. And a little bit of a theme here also involved in novel affinity lagging discovery. In particular, you know, collaboration between DIAX one of my former employers and why discovery of a novel affinity lagging for purification of a factor factor eight products. And as well in single use technologies, prepack column technologies and more recently in continuous chromatography. In all of these cases, you know, my role was, you know, a role in combination with many, many, many other people, obviously, and so one of the points I think that I want to make is that it really does take I think a community. And to develop a and successfully introduced, you know, a new technology or a new way of operating into our industry and that theme I think has, you know, been shared by many of the speakers. And the importance of communication of standards of, you know, developing strong communities of practice and, you know, common language and common guidance is I think is really critical to this process. So, these types of, you know, forums are important to that process. And I think it's important also to stress that these are my own personal perspectives but I think they're aligned with, you know, my current employer resilience who's really focused on leveraging innovation and new technologies to develop the fault and new platforms for production of techniques. So, you know, bottom line up front my overall conclusions are that we can as an industry introduce new technologies, we have demonstrated that ability, but there are some challenges to the process. And I think one of the things I've learned is that the benefit really needs to be consistent with a level of effort. So, talking about a technology that's going to require a lot of work and effort to implement. We're unlikely to do that for a modest benefit so that's part of the evaluation I think of of new technologies as as we as we look at where we might implement them in our processes and our product development programs. The timelines for adoption of innovation are long compared to other industries I think that's been true throughout my career I think it's, it's still true although I do think we're getting better at it, but I do think, you know, this is in part due to the timelines for our product development. You know, my friends in the software industry talk about, you know, being disappointed that they don't launch a new product a year from when they start obviously we think in terms of decades and I, I think it's hard for the new technology introduction process to move at a very different cadence from the product development process so to some extent, I think that is part of the, the recognition of those long timelines needs to be part of our approach to new technology introduction. So if you could go to the next slide please. I just have a few slides here but this I thought was one useful example that I've been tracking. And I'm sure many of you have is the adoption of single use by reactor technology in our industry, but just thought it's a useful example in reflecting on how long it does take to really truly adopt a new technology and thinking into the first introductions of single use by reactors in the late 1990s with the wave by reactors which, you know, obviously, those of you that are rocking motion by reactor, not really representative of the stir tank by reactors that are used in the process. So, you know, that led to enough interest and excitement that the first CSDR stir tank type by reactors single use by reactors were introduced a little less than a decade later, and then the first 2000 single use by reactor which is sort of our current most commonly adopted production scale for single use right now was introduced about 12 years after after the wave introduction and then finally about 15 years later. The first FDA approval of a biopharm, a commercial biopharmaceutical manufactured in a single use production by reactor was was successfully accomplished and and even now the slides up here show, you know, sort of a 15 year view of the installed single use by reactors compared to stainless steel both in volume on the left and in number of bioreactors on the right. This is from a database trending supply and demand trends for biomanufacturing capacity that helped develop a consulting company called BC which is now part of the video and still a database that I find useful. You know, it shows that even now we're continuing to adopt at a greater rate single use by reactors compared to stainless steel but this is 20 years later so adoption cycle of a you know very successful new technology in this case. This is somewhere in the order of one to two decades but depending on your perspective. So finally next slide. And we'll get to my last slide which is really just an overview of the challenges as I see them to new technology adoption and the opportunities and things that we can do as an industry to to improve our ability to do this. One of the most important challenges is the risk associated with technology adoption and this has been highlighted well in the, in the NASA report and also in the discussions this morning. You know, they're there penalties for delays and setbacks and any pharmaceutical development program and these are significant. And as a result, you know, the perceived risks for new technology adoption are. You know, perceived in the context of what if it delays a important, you know, biopharma development program. As a result, you know if we can develop a product with conventional technologies were more likely to do that nobody wants to be the first to develop a new technology and as was highlighted in the report and before the first person to go through that approval process, you know, faces the double burden of, you know, justifying and supporting the new technology as well as their own product, which is a heavy lift. Second challenge is that there's there's no good time to implement new technologies and I think Todd mentioned this at the very beginning, you know, as as our timelines get compressed this becomes maybe even more and more true. It's it's hard to find a time to slot in, you know, the time that's required to implement a new technology when it may require more time to qualify new equipment to train operators on a new way of operating. And this this inherently will slow down the first few times a new technology is adopted. So how do we manage that. I do think has been highlighted before our industry has invest relatively little compared to our revenues in new technology compared to other industries and, and I think that's also perhaps re action to the fact that our manufacturing costs are quite low compared to the sales price of our product so you know I think we are seeing that improve and you know the Rohan and that Norendra's talk today, I gave some great examples of, you know, the potential impact that proactive investment can provide as companies, you know, really do develop exciting new technologies. As I was highlighted this morning, I think, you know, part of being better at this is is being more proactive at investing in new technologies as an industry. And part of that is, you know, justifying the value and I think the benefits are often underappreciated we we focus too much I think on the cost and timeline benefits only while under appreciating the potential to add real value to our programs and products and, and to the supply chain as we've all, you know, you know, experienced within COVID the, the impact of fragile supply chain on on everybody is significant and part of the value that we can bring with new and new technologies is, is the ability to, to have a more robust supply chain across our industry. And finally, I think IP uncertainty can be a challenge that people face when when looking at new technology is obviously freedom to operate is paramount to the ability to supply. And, you know, but fortunately, there are many opportunities to improve our ability to innovate and I think some of the strategies that that I think are most important have already been highlighted really today. And those include consortia to allow for pre competitive collaboration and groups such as nimble and, you know, others are certainly important, I think to that objective regulatory engagement to provide mechanisms for feedback to innovators so the ETP, which is highlighted today I think is a great example of that and there are others that Sarah talked about in her presentation I think those those are those are tremendously important and finally standards and guidance documents to provide common understanding and vocabulary. With, you know, my focus and interest and continuous recently I've spent a lot of time with ICH Q 13 the recent draft and think it's a really great example of a document that provides a good insight and the use of the annexes to, you know, provide even more granular perspective without, maybe as rigid, you know format as the the actual guidance I think is also very helpful and that was, you know, I think done well with Q 13. And then finally, as I mentioned earlier proactive investment by industry I think greater willingness to do that across the industry will is important as well. Well, I had done, you know, without it just like thank you for your attention and pass it on to the next speaker apologize for probably going over a little bit. Thank you very much Tom, appreciate that and our next speaker moving right along is Dolores Hernan, who was a quality specialist in the human medicines evaluation division at the EMA where she focuses on the development and characterization of control release delivery systems based on micro and nano technologies. Thanks Dolores and welcome. Hello, good morning everyone. First of all, we would like to thank the National Academy of Science and the FDA for inviting us to share with you our perspectives. We believe we are very much aligned we are all on the same boat on this, and I would like to share with you our perspective on the challenges and opportunities offered by innovation. So if we can go to the next slide please. Yes, so the EMA has been mentioned several times I believe you all are aware. So I will go quickly over this so as you all know, same as FDA. Our mission is to foster scientific excellence in the evaluation and supervision of medicines to promote public and animal health. Next slide please. So in order to achieve our goal and to address our public health mission, we are knowledge that innovation is needed. We need medicines of the best quality, which are highly efficacious, which have a good safety profile. We need medicines that address an unmet medical need. And we need to avoid shortages to processes which are improved and processes which are reliable to increase the flexibility and agility, increase years and in the environmental, and decreased environmental impact that was mentioned earlier by one of the speakers. So we are an open forward agency and we encourage innovation. Next slide please. I cannot see them in full. Okay, so reflecting a little bit on the scope of the session, which are the general challenges I see if we if you can press the next button. Yes, again please. I see that both regulators and industry. Generally, we have a traditional mindset, and this can create fears. Next, next one please. And next one. So industry has fear that their innovation would not be accepted by regulators but regulators as well on our end we need to have early visibility of which are the companies developments to ensure that we are prepared. Next one please. So we all need training to make sure we understand these innovative technologies. So that we develop appropriate processes and then we regulate them accordingly. Next slide. Next one please. So yes, we are knowledge industry has to do on a front capital investment that is one of the risk. But we also need to constantly evaluate whether our regulatory framework is appropriate and whether there is the need to update our regulatory frameworks. So we are knowledge that there are challenges at both ends. And then I will go over the opportunities we see next slide please. With regards to the those were general reflections of challenges I see between in among industry and regulators, but with regards to more going more in detail technical and regulatory challenges. We all see that there are more and more complex systems and technologies under development, for example, additive manufacturing platform technologies. We have seen more progressive control strategies, for example, based on performance based approaches, artificial intelligence that has been mentioned earlier in the workshop, advanced automation and advanced process controls. We have also seen portable modular systems that and bedside manufacturing and decentralized manufacturing approaches for example in the case of advanced therapies medicinal products. And with regards to the complex systems and complex medicines I was referring to, for example, here a little bit companion diagnosis and borderline products. Next slide please. Seeing all this, what is EMA doing. So, back in 2020, we conducted a horizontal scanning, horizontal scanning activities to identify which are the innovations that are coming and make sure that our regulatory system is capable of regulating those technologies and novel medicines. So, this is a, I, you cannot sit here but on the lower part of this slide there is the link to this document, where we covered the, the outcome from this horizontal scanning. This was done is that dive deep report done by our police on the regulatory science. Also, meetings we have with industry stakeholders to understand from them, which are the technologies and the challenges they see in the coming in the near future. We could work together and prepare for those. So, given the scope of the meeting here I try to outline a little bit which are the core recommendations relevant for today's discussion. So the one, one of the goals and primary recommendations from this person scanning activity was to facilitate the implementation of novel manufacturing technologies, and another one to promote research and innovation in regulatory science. Next slide please. So, in addition to this, what is the EMA in collaboration with the European Commission doing. So, importantly, and I think is relevant for today's discussion and for everyone of the wellness in November 2020 the European Commission launched the pharmaceutical strategy for Europe. And basically what this means, we are conducting an analysis to try to identify which new technologies among other areas and which new approaches are being developed to ensure that the European regulatory framework is future proof and support industry in promoting research and technologies for the benefit of patients. Next slide please. So, which are the opportunities that we have to engage on CMC dialogue with us. Next one please. So here I try to outline the different opportunities we have. One of the speakers mentioned some of them briefly earlier. The innovation taskforce is a multidisciplinary platform for early dialogue to have some dialogue with us on legal, scientific and regulatory matters. This is, as I mentioned, an early dialogue at touch base so that at an early stage you can start dialogue with us and discuss your concerns, present your technology, and then we can take this forward. In addition, this is from EMA but EMA works in collaboration with all the national competent authorities from all member states in Europe. And in 2015 collaboration was established between our EMA innovation taskforce and the innovation offices from all member states so we can have a dialogue, identify training needs for the European regulatory framework and take decisions that then could be implemented across Europe. Another entry point to get support from us, you may all know, is the scientific advice and protocol assistance platform. And also importantly, was mentioned in one of the earlier presentations, which forum, which forums are available to have dialogue with regulators as an industry and not single meetings. I would like to stress that at the level of the quality working party and the biologist working party, which are formed by a EMA secretariat together with representatives quality assessors on the small molecules and biological area from all member states. Once a year, we have meetings with our industry stakeholders to discuss topics of common interest. So this is one of the platforms we have available. We are also working on the development of a platform to strengthen our dialogue with quality and GMP inspections and you will be hearing from this from us in the near future. And also we want to acknowledge that academia plays an important role in innovation. We have an academia office and we believe that the collaboration with academia and learned societies is an important aspect that we should keep in mind. Next slide please. So these, I wanted to put as well this into global dimension. We believe that developments are done in a global manner. And in this regard, the EMA has collaboration with understanding agreements with several agencies across the globe. We are also a member of different international platforms for dialogue. For example, ICMRA, international platform, regulatory forum, ICH. So I think it's important that industry work together that we don't work in silos, the collaboration with academia and research institutions, and that we all and daily aids with regulators so we all work together to make this happen. We cannot work in isolation. An important aspect that I wanted to bring to the table is that applicants should allow regulators to discuss their applications among themselves. We have found ourselves in situations where we had a new technology. We wanted to discuss approaches with other regulators but we didn't receive the approval from the company. I hear several times, oh, but you know, there is an alignment between regulators but we need the support from industry and the openness from industry to allow us to have discussions around new technologies to make sure that we have tools to try to align our regulatory expectations as much as possible. And of course, another aspect we should consider as well whether there are national regulations at regional level that may prevent to share and discuss commercially confidential information among different authorities. So next slide please. So my day home messages is that innovation is needed for the benefit of public health. I believe that industry and regulators set the responsibility to make this happen for the benefit of the patients. We have challenges but we should work together to overcome them and collaborate. And I believe that early dialogue is essential to pave the way and ensure that there is a mutual understanding. Next slide please. Thank you very much. Thank you very much Dolores. I appreciate your comments and for for keeping us moving along so very dense content but but very well appreciated. Thank you. Our next speaker is Malcolm Barrett Johnson who is managing director and regulatory strategy expert at pharma medic consultancy limited. He is a physician with pharmaceutical experience in medical and regulatory affairs. Welcome Malcolm. Tim thank you very much indeed and it's an absolute pleasure to be invited to speak today. So I'm across a pond I'm based in London. So it's coming up to dinner instead of lunch on this side of the pond. What my background is in general just to give you a very brief understanding of why my views might be of any importance at all in interest. I used to be a regulator. So like Dolores I work with the MEA at one point but I work for the MHIA. And as you know after vex it now we are sort of outside of the fold. So the MHIA is slightly different. I work constantly with the MHIA in a consultancy regulatory capacity. I'm also the director on three biotech companies as well. Manufacturing isn't really my area particularly so I think oh God what's he going to be talking about my more medical affairs so I've actually as a medical director and a number of companies including big ones like AstraZeneca, Pfizer's MSD's in the UK. I'm going to just compliment and say thank you to Janine Jameson. Janine raised an area which I think may act as quite an interesting straw man for discussion just going through just to highlight a few points as a regulator, an ex regulator and someone who works in the industry day by day. This thing is a reflection paper by FPA and FPA the European Federation of Pharmaceutical Industries so they're part of IFPAMA the International Federation of Industries. This issue came out in November 2020 and it was a reflection paper reflecting on the way that manufacturing in one area and sort of small manufacturing units could be used but it does raise a number of issues. Next slide please. Thank you. So the European arena, we are the second biggest area for wanting pharmaceutical medicines and we are a huge sort of by all of them were constrained obviously by as you are in the States by by costings. Everything is very patient centric so I agree completely with what the law was saying. The FDA, the MHI are very patient centric as indeed the FDA are. And the key objectives as you were no all too well are to ensure medicines safe, improve lives available to patients globally and preserve safety efficacy and quality the three cornerstones of the triumvirate stall. And I know the industry has been investing huge amounts in modernization manufacturing and each supply operations generally. This is to very basically make sure that the supply chains are adequate. What this does it also raise is something we've all been through recently yourselves in the States are still going for it and we are also well in the UK and Europe. COVID. What we saw from that was a an absolute need to get supply chains in place. We had a bit of a tiff with the European Union is you may well know, in terms of COVID-19 and the supply of vaccines to that. There was some degree of misunderstanding I think in terms of supply chains, but what it did raise and what was very interesting was the importance of manufacturing and the importance of getting a supply chains right. Standing slightly outside the manufacturing field to my, my view, manufacturing doesn't get the credit credit and impetus that you should do within the companies themselves if you're the medical director level you know about manufacturing you understand the quality she's a course you do, but you don't really see that and I think we've brought manufacturing much more to the fore over the last year year and a half two years, and all good for that too. And the other thing which I think it's also brought before is a need for universal access. We're not we don't live in a bubble, we don't just live in the States we don't just live in the UK. We have to think about the global perspective on that. And as I think he was Kelly Rogers said earlier one of the other sessions she said, things are very complicated things a lot is going on and indeed they are. And who from GSK early also said, we need to look at the international components of this under ICH is incredibly important. So supply chains in disruption are to my mind, one of the most things important things we need to look at. So this portal manufacturing that we're discussing here is I think one interesting area to look at. So you're looking at new technologies. This was brought out in the report to 3D printing, supporting specialization, supporting production or personalized medicines which we talk about a lot on the medical side. I think a lot of us on the medical side I don't fully know what that means. Can we actually dispense closer to the patients. Also, it's been talked about can we have bedside manufacturing. Can we manufacture to the patient but very, very locally that being a lot of advantages. At one point I was involved with the Kurdistan government, where we had a lot of falsified medicines a lot of children dying, because the manufacturing process wasn't there locally. The vaccines weren't there. A lot of the tablets are being given were made out of straw. It won and sand it was not a pleasant sight. It was a pleasant situation. So manufacturing is vital to this and getting it local. Manufacturing has to be agile as well. And this has to be basically addressing things as well from the green agenda. Things like global pandemics have brought that to the fore. And we have to see that the speed of manufacturing is also increased. Next slide please. Part of this and what's what's an interesting area to look at is something that came out of the European Commission. It came out very recently at the end of last year beginning of this is the EU pharmaceutical strategy which the law was I'm sure was working with very closely under the European Medicines Agency. And this is very much ensuring preparedness for manufacturing technologies is bringing out areas such as security manufacturing, making sure that supply line is available making sure that what we have available to us is fit for purpose. And from my perspective and although I'm sitting in the UK, I can claim some degree of Europeanism out in Italian. It's making sure that the this, you know, the European side has a strong voice globally under ICH, and indeed with yourselves at the FDA as well. And also, I think it also brings to the, the, the four things like manufacturing diversification, which is vitally important. Thank you. Very recently we've had something called the European Health Emergency Response Authority set up called HERA. And it could be named after the Greek God, but actually it could be HERO. And this is basically being set up by the European side to make sure that we if we have a situation like we've had with COVID, we don't get caught off guard again. Manufacturing is a very central part of that. And this is why the pharmaceutical strategy emphasizes it. I'll say very quickly at these pods because I think it encompasses a number of interesting areas. These are multiple units that can be housed at a fine set of pharmaceutical operations, but can basically be copied and copied and copied to basically become fully autonomous and can be replicated in an equivalent manner, the process and the quality that you might have in one country to another site in another place. And this should lead to consistency, high production volumes, and a greater patient responsiveness, whether it be local or globally. Next slide please. Well, they also raise a number of interesting issues about acceptance of things. If you go down this module approach on a global basis, is the site itself autonomous and mobile, but also where does that sit with GMP? I do lecture on GMP, and I know just how important it is to make sure it's replicable and make sure that wherever that unit may end up, that can be replicated back to GMP, which kept where it was in the host country. So GMP is a series of registered establishments. We can validate against it. And how do we sort of validate against ability and validation studies in a changed location? It's an interesting area. And something which I thought was very, very interesting when I saw this as a concept. And how do you do things against insurance too? How does insurance cover things like that? So general recommendations out of this report and things which I think are very important are things under ICH. Are we taking those ICH areas adequately forward in things like portable autonomous manufacturing? Are we taking them forward in areas of emergency usage, which we all know too well under COVID? Tom mentioned this, I think, but generally before, with his work on ICH. But are we actually building those discussions between our manufacturing colleagues and our quality offices, whether it be the MEA, the MHO or elsewhere? And I'd just like to finish on another couple of points. One thing which I do think is vitally important and came up in discussion I was showing earlier is manpower. And one thing that came up in this consensus report too, manpower, but not only manpower, but education for that manpower. The technology we're seeing now is so advanced that it wasn't even an existence when I was a doctor several years ago. We're treating people with things like immunotherapies, which didn't exist. Key Truder was an amazing technological advancement, which I didn't even understand when I looked at the original data from SD. We need to educate people and constantly educate them. And we need to do that as well for the agencies. The MHRA, and it's a bit of a problem at the moment, is actually dropping a third of its staff in the UK. I don't know if the FDA know that. And everybody else on the MHRA side is reapplying for their jobs. It's not right, it's down to money. It's partly because we pulled out of Europe. I'm not a Bexiteer, but that's putting a lot of stress on the MHRA. I'm sure the MEA and indeed the FDA got similar problems with money, but also with training. I think that's something we on the industry side can help with and probably should help our colleagues in the agency side to make sure that they're trained properly and understand the problems that we're having on the industry side. So Tim, I'll leave it there. I hope I haven't gone too much over my timing. Thank you. Thank you very much, Malcolm. Appreciate it. We're doing okay here. We'll fold you're on. Not very helpful and thought provoking comments and we'll pick this up in the discussion. Last speaker in this, this short talk session is Mike Oregon, who is owner and managing director of Horizon Controls Group, which is a full service digital process automation company founded to promote the best that the field of engineering has to offer. Mike, welcome and thanks. Thanks, Tim. Can you hear me okay? Yes. Very good. Thank you and good afternoon, everyone. And I'm really honored to present here today on behalf of Horizon Controls Group and the International Academy of Automation Engineering has been a fascinating conversation up to now. And I think a number of the points that I might raise today have already been covered, but I think just Malcolm's finishing points there on manpower and education are something that's going to really resonate with what I'm about to say here as well. So just a little bit of background on myself. I'm originally from Cork in Ireland, and I moved to the US in 2004, and I'm calling in from Bluebell in Pennsylvania today. And as the founder of Horizon Controls Group, we're an automation engineering company who are very much focused on and 100% focused on the life science industry and providing solutions to the manufacturing and the laboratory space within those in that industry. Additionally, we have an area of business that's very focused on training and the upskilling of people on the different platforms and use in the manufacturing space. And in addition to within Horizon Controls Group, we have a growing area of our business that's very focused on the mixed reality and the augmented reality virtual reality applications for manufacturing and laboratory situations. That encompasses machine learning, object recognition and a movement for our business forward with digital twins. It brings me to a point where I might mention a project that we are involved in additionally at this moment in time with MXD. It's funded under the CARES Act, and part of the remit is to install digital twin technology at two life science manufacturing companies and to test the benefit of the deployment of the twins in the event of another national emergency. So really to stress test the benefit of the digital twin. As part of that project, we are working with MIT and we are conducting a survey of companies and of the government, the FDA and bodies and also academia. And if anybody is interested in participating in that survey with us, and we'd be very keen to have you participate and then get a readout afterwards of our findings, which I think is very relevant to the topics we've been talking about today. And hopefully you'll feel the same. On the area of the International Academy of Automation Engineering, it's a not-for-profit automation and digital manufacturing education and capability building entity. I came up with the idea back in 2012, and along with some of my colleagues that are on the call here today and would have put a lot of effort into it over the last number of years since 2016. So just to give a mention to Malcolm Jeffers and also to Gemma Doyle on the call here with me, a lot of great effort. We stood up a life science advisory board in 2016, and some of the advisory board members are on the call today. Specifically, I know Sally made a number of very worthwhile comments earlier, specifically around the change management and the people aspect of that as well and coming back to Malcolm's comment just in the previous conversation around the manpower and education. I think this is a nice intersection point for us. The life science advisory board is made up of leaders from a number of companies, specifically Thermo Fisher, Biogen, GSK who are on the call today, Pfizer, Takeda, Genentech, Vertex and a number of others. And then we'd encourage participation from any of those that are interested. Typically, they're leaders that have a global automation remit or maybe data science remit and analytics, and they bring a lot of taught leadership to the table. And then we leverage what feedback we get for them. We do some research and we share with them, and then we take that into our education programs. So we've a very comprehensive education program built out and it's available online. And we've also worked with Nimble and delivered on some some projects, most recently the spider to project, which was done in association with NC State and Worcester Polytechnic Institute as well. And there was a cohort of maybe nine participating entities on that project. I think it was one of the larger projects that Nimble had led and it was very successful. In addition, we've done projects with MXD and we're also one of the founding partners of BioMaid as well. So that's just a little bit of background on the IWAE. And it kind of leads me nicely into the maybe the next slide, which is an area that I want to speak to. And it brings us to a project that we were recently involved in with MXD. And it's very much similar in the approach and the outputs as to a lot of the conversations that we're having with the committee today. And it's focused as you can see there around the analysis of the advantages of and the barriers to adoption of smart manufacturing for medical products. And this came about shortly after the country went into the world went into lockdown and we started a project in May of 2020. And our remit was to identify and interview a number of medical product manufacturing companies specifically in the US. We identified over the course of time, 10 companies, 10 participants, and nine of those were individual sites within the US and one was a corporate entity. So it gave us a very interesting perspective. And what what we did was we set out a program whereby we focused on the traditional digital transformation and technology adoption approach around people, business processes, technology and regulatory affairs. And we identified leaders within each of the organizations that had responsibility in those areas. And then we set about a engagement which had a comprehensive online survey. The second part involved us utilizing the bio forum digital plant maturity model where we did a deep dive on each of the areas and the questions in the DPMM such that we could get a pulse on where that client sat from a maturity level. In addition, we did a comprehensive interview session with each of the stakeholders, and we basically then generated a lot of content. We de identified the data, and we provided a report back to the FDA, the OSET Office of Counterterrorism and emerging threats and department within the FDA and would funded the project. And at a later slide here and I'm sure as the committee shares the slides and content we will be providing a link to the report that was published and just recently on October 1, and by the FDA. And some of the what you're seeing on the slide now is just one, one, bringing up a couple of slides from the study. And but I'm not going to go too deep into it, because it's much more comprehensive and I'd encourage you to read the actual report that's available online. But what we were using here just a framework and the transformation map that shows a lot of technologies as it's applied to our industry. And basically, we worked each of these technologies into our survey and into the plant maturity model and into our interviews, and we extracted as much information as we could from the participating companies. And we collated all the information and we came up with some interesting findings. And specifically if you just just to move the text will change here just on the next slide movement. So these are just a sample of some of the transformation map items there it's a little bit of an eye test on the left so just figured out make them stand out a little bit. And but specifically you're seeing things like the artificial intelligence and robotics that we spoke about earlier this morning and the future of computing and again I think that's interesting in the context of where where industry is going in the next number of years and I had an opportunity to attend a conference just before COVID and in MIT last year and around the topic of the future of computing. They brought in a number of industry leaders from the IT space and Google and other MIT researchers as well, and they were focused on quantum computing and how it's going to find its way into industry over what they felt was that it's going to be about 10 years from that stage before it starts finding its way in. But I think when you take that into context now of the acceleration through COVID and what we're doing with data these days it's going to push even further and the advent of quantum computing in manufacturing I believe. So some of the other areas there the wrong focusing on leadership and digital transformation of the business processes and then innovation and the whole topic for today. So these were just some of the extracts from the chart on the left. And if you move forward on the slide. Please. What one of the outputs that we have inside our report is this quadrant here which is showing just a kind of a benchmark for the digital mastery for some of the participating companies and the chart that we have was an extract used under permission from a book that was previously published around the topic of digital transformation. And you will see that the two blue dots there was originally from the book. And that was indicating the benchmark of pharmaceuticals and manufacturing and just manufacturing at large in 2012. And what what you're seeing then there is with regards to digital capabilities on the vertical access and the leadership capabilities on the horizontal. You're seeing the placement of our participants on the red dots. And what you know what you can read for that is that there has been an advancement as specifically in the life science industry since the 2012. Now again it's a small sample set and typically the companies that participated in the study came from a background in vaccines manufacturing PPE manufacturing at therapeutics and medical device slash diagnostics manufacturing. So again a small group but I think it was a valuable insight into the status of the industry and a relative to the topics under study. And I think it also teases up a number of new opportunities to continue studies and to develop out on what our findings were here. And if you just move forward just to give a bit of context to the quadrants here and just move forward the text will change on the left. And what you'll just see if you jog forward and you see that the beginners. And again it's fairly self evident the tech wonders. I want to to next on the conservatives and then lastly the digital masters. So what was noteworthy on that and again I listened carefully to a role in earlier and role in was one of the sponsors of the program that we rolled out from the probably the Biogen were an early adopter of that content and they rolled it out at each of their facilities. And I think again when you when you see the level of advancement that the likes of Biogen have made you see that that a number of companies are moving strongly towards you know the digital mastery. And what was an interesting point that one of the participants mentioned that the digital transformation is not so much a transformation but it's an evolution right it's ongoing it's not a there's no definitive end here in this that it's a constant evolution. And I think that's that's evident from some of the conversations here today as well. So again just if we move forward on on this here just to maybe speak to some of the findings additionally. And again I'm taking some of the slides out of context from the survey. And one in particular that's that was stand out in the survey that we were doing, we can jog forward. I think this will resonate with the broader group might be having some some updates delays area so it's just coming up on my side there now so one of the questions that we worked into our questionnaire was asking manufacturers to put on the list of suggested actions from the 2020 National Academy's report, which I think it's very pertinent to bring this up today. And you'll see that there was a number of the actions listed down below and there's the responses are in the vertical columns above. And we've, we've bolden those that kind of stood out the most from the responses. And therefore become familiar with condition based monitoring approaches and provide incentives for their use and I know that was a topic there around the incentives that was discussed at length this morning. So just thought again just some interesting feedback for the committee here on using some of their data in a different context and with a different pool of people. And I think there are five that inspection staff have the expertise to understand the technologies and the best practices in their application. And I think again we spoke at length before lunch around the benefits of upskilling and coming back to Malcolm's point here again on manpower and education. I think we've had more lunch about that the need for it to somebody education, an ongoing and continued education within say the FDA, and but also within industry and I think what we're seeing at the moment is unprecedented movement of personnel within the companies. A lot of mergers and acquisitions that have gone on. And is that a disruption or is it a benefit to the digital transformation and adoption of technologies. Okay. So I think we've addressed some of the kinds as you as you dig into that and, and again, just with considerations and time. I think we've addressed some of those in our study so you'll be able to find that but again I think just the unprecedented movement in the last number of months of personnel is is going to be another challenge on top of education and and the baby boomers retiring and, you know, compete competition from other industry verticals as well so there's a lot of challenges out there. So I think what you know what we found as well is that some of the companies that were advancing their digital transformation were conservative in their feedback and kind of humble in their approach to their advancements. When you compare them to some of the other companies that were maybe not as advanced. Those that were advanced were maybe, as I said, being humble and maybe being tough on themselves because of what progress they were making which is a considerable lift for companies and challenges and some of the feedbacks that we were getting were around the competing priorities which is mentioned earlier, legacy systems and insufficient funding and, you know, just the need for stronger leadership as well right so I think the migration of talent is going to be a challenge to the, to the strong leadership standing place to guide any one entity forward. And so if we if we move forward here I think is maybe done towards the end of the slides here, and then in kind of wrapping up I would maybe just speak to a couple of points here that from a key finding this there on the technology front and a number of the companies were saying that they're slow to adapt new technologies for reasons and outlined previously but what they're looking towards is other companies and other industries are proving the technology first to basically take out some of the risk from from them subsequently deploying it. And one interesting observation I made during our study was a one of the participating companies was part of larger, what I would say, and within their organization, they were the medical manufacturing arm of the bigger company, but elsewhere in the company they had manufacturing entities that were making huge movements in the digital transformation space, and therefore as a byproduct of their progress, the medical division was able to leverage some of the technology deployment that they were making. So I think this kind of stands out to one or two of the points earlier today that of adopting what's been done in other industries, more quickly and partnering with those industries just for sharing of the knowledge, but again that was something that just stood out to me they were able to do it all under one umbrella, but wherever we can, and obviously trying to leverage what's been done in some of the other industries. So the, on the technology front some of the key takeaways again a number of the companies looking towards big data, and the adoption of cloud computing, and also their focus from a technology perspective around cybersecurity, and specifically related to related to AI and machine technology, and lastly then on the technology front around robotics and robotic process automation from a business process improvement on the regulatory side of things wanted takeaways was around headcount to be able to implement more broadly that was seen as a challenge and a barrier. And then we spoke into somebody others that was related to the National Academy side earlier on the people side of things low levels of training and unknown levels of training within organizations. So basically you could present that as visibility of training and maybe insufficient levels of training was seen as a barrier to moving the digital transformation forward as well. And I'll finish on a last point that it's most likely that we presented one one selection of slides and asked them what was most likely to be there areas of training that they would focus on and the leader on the result there was around operational excellence. And so again not necessarily technology focused, but more on the operational excellence side was it was the leading result there but again you'll find a lot more context and a lot more information and on the slide on the reports per the links that are shared here and just leave with a little bit of humor. At the end of this, there was one comment fed back to us and said that, you know, with regards to and relative to the international and the international challenges and the compliance challenges and references earlier to harmonize harmonization. One person commented and said how are we going to achieve harmonization when we can't even agreed on the agree on the spelling of the word. So I just thought that was an interesting piece here given all that that was said previously so again I thank you for your time. Happy to answer any questions in the follow up chat. Thanks. Thanks very much Mike for that. And, you know, perhaps we can harmonize the conversation and then during the community discussion by whatever spelling you all would like. And thanks, Tom Dolores Malcolm, as well as Mike for for your comments and now we're moving into the community discussion, and we really want to hear your voices. And, you know, this is an opportunity for you to speak up on what you view as the hurdles to innovation for the community as a whole. This is particularly important because we have, you know, preparing for tomorrow's discussion on solutions and a path forward. The speakers in session for tomorrow morning and Sally who's preparing to moderate that discussion are dependent on you in the community to speak up and talk about what these hurdles are what the gaps are today that that we see today, so that they can begin to make solutions in response to, you know, these observe gaps, both those that have been spoken about by the speakers, and those that the community as a whole have voiced. So I urge you, please to use the slido issues, I think there is ideas, excuse me, if you just have a comment there. I think it's something that you'd like to raise on something you want to talk about we appreciate that you can use the q amp a to pose questions to our speakers that react to their remarks, that would be appreciated also we'll use the for both of those, but I'm going to get it started a little bit while people are getting going on that with a couple of my own questions that I've been thinking about and we heard about innovative technologies and existing mechanisms and sessions one and two so questions here and I want to get see see what people have to say and we'll we'll we've got the panel up here on the on the screen so I won't call on you but you're certainly welcome to volunteer first others raise your hands as well. I have a question that we haven't, you know, completely and overtly spoken about, but I really like people the voice is, you know, with regard to the technologies themselves. Do people feel like that the pace, perhaps the slow pace of implementation is due to insufficient technical readiness. Fundamentally, you know, is that part of the problem, or is it not part of the problem. Any any thoughts on that. I'll start I guess I do think that that may be part of the problem, Tim and I think that, honestly, part of what we saw in some of the examples today I thought were good examples of investment in technologies ahead of deployment, particularly Norendra's description of technologies that GSK was investing in might be a good example and, you know, in from my perspective, by doing that. Now we're better positioned to implement that technology when appropriate application comes along and I think I've heard from a number of my colleagues in industry that, you know, a lot of times that by the time you know you need a new technology. You don't have the time to develop it and so if we can be proactive enough to invest ahead of the curve in technologies that we think we might need. I think we'll be in a better position to deploy them when when the when the real need materializes. Actually, I think a good example we have seen with the COVID vaccines with the leaping nanoparticles although we had on patrol a proof few years ago, then we because the technology was available as several other companies have been have been using that technology and have been able to develop the vaccines in such a speedy manner. That's right as well, Tim, because you know, the technology we've seen in the COVID vaccine is something we can use for other things that one of the biotechs I'm involved in is using that technology basically something which is different. And I think also I think there's a lot of feeling and I remember this from my regulatory days. You're not scared. But you know, as it came out of the report, a lot of the technologies have in the past been developed for one product or series of small in a small areas of products. So we can get down the line of developing a technology which can be more applicable to a wider range of things are better. Maybe that's something we should think about and say that we're going to give grants innovation awards and stuff to technologies which can have a wider remit there may be a very narrow group of products that may be easy may not be. But when you're looking at artificial intelligence systems. That's obviously an error on the control side where you could do that. So I think that's a very interesting question. Thank you. Any other comments. Thanks. Yes. Actually, we have seen that with other technologies for example continuous manufacturing the first sponsors you will know that use this technology that they have been using the platform they develop with few adaptations for other products and they reach the market. In a more, more quickly faster. So I think there is an advantage there. Of course it takes time and investment to develop the platform but once the platform is there then of course they the development goes quicker. If I was just to add something as some feedback that we often get from from clients when we're engaging on the education level is for more of an industry academia and engagement because what they're finding is that with a number of the graduate graduates when they come out that it takes quite some time to get them up to speed to be autonomous at the plant. And so that's not just from an automation perspective, but I'm just saying in broader terms as well. So I think we need to kind of continue to evolve in the education space to make sure that what we're developing for the industry by way of personnel is appropriate and can help the companies to work faster as well to adopt faster. Thank you, Mike. If I could just add to that. I, my experience is that should be bidirectional. Also, because the students that are coming in often can, especially in areas like digital. They can sometimes affect the thinking of people that have been in the industry for a long time. Rex looks like he's raising his hand. Being in education, I guess I have to say something about that. And particularly since I'm on the side of education that really uses the digital technology and the modeling and the control. And I think the challenge for the pharma industry is actually to attract and retain such students. There's plenty of examples of students who spend a year or two doing applications, one of your companies, and then they join a technology company, a software company that gives them financially much bitter perspectives. And, and I think you have to find a way of motivating and engaging them and keeping them there because that talent pool is on demand across many sectors. Yeah, that's absolutely true. And I think, you know, more and more training is a core competency for all of us, right. And the more we can come up with creative solutions to train our workforce in areas that are important, the better. But we see that as well in the data analytics field. I mean, you can't hire people from top programs that are going to Wall Street or wherever making, you know, way more money than we can offer them. So we have to come up with another mechanism to get that talent into our organizations and train. Yes, this was another topic that I covered in my talk, the partnership with academia, because we all know some, you know, the basic research and so on, generally is done by academia and then it's transferred to industry. So I think the partnership and the collaboration among industry and academia and regulators as well is key to make this translation of these technologies into the market. And one thing actually on that point to him and to bring two things that you mentioned together to some extent as well is is my son's working in but in aerospace. He's he's he's he's qualified from aerospace and rocket science. It is rocket science. But you know what I see from what he's doing is you could take a lot of the technologies on the academic side and bring them over to the other side. We see this also on the business side generally we don't always bring together the farmer components of a company of an academic unit together with the business side. It happens in Kings in London where we've got a very strong development team at Kings London got a business school they don't talk. Sometimes we don't you know could we get I don't know the Swansea or the Manchester Aerospace Group to be talking to the farmer group academically but wider. You know we've also got the Crick Institute in London two and a half thousand PhDs in one building over 12 floors amazing. What they do with it goodness knows they don't develop it very much for this terrible but if you got them involved together with the tech team Google and you know the technology son the digital side is over the vote from them at St. George they don't talk crazy. We need to get the industries talking together with the academic centers also talking to industry but also internally perhaps. It's very interesting. Thank you Malcolm and the, the, the, both the adjacent industries aspect and the learnings there you know is a really, really good, you know, thought and I think that the business the relationship of business, you know not only as perceived by the industries themselves, which is basically framed by their own viewpoint of the business, you know, and so, perhaps the academic business area, you know, is an opportunity to look more at the system level, you know, rather than at the individual you know with regard to that because the individual farmers have their direct business interest or direct portfolio interests, you know which of course comes first because of the way things are set up in the system. And you know I'm very interested in how, you know, as a whole and as a community, you know we can look at advancing this at the system level. You know, when you, when you think about, you know, what, what do we own collectively, you know, and people have the interest in preparing for and enabling the manufacturing of their portfolio with agility and all that maybe we're not doing as well as we we could in that, but then in saying how do you raise the whole of it. Well, no, no single entity actually owns that, you know, we have to have to tackle that collectively. Thank you. I have the next question that sort of move on to and thank you Kelly for prompting it you know it's kind of a follow up question from from the previous session on existing mechanisms and you know really we'd like to at least ask people if you know how are the existing mechanisms doing. We've inventory them a bit we've heard some you know viewpoints on existing mechanisms and some opportunities that that are in front of us. But I'd love to hear what people's views are on whether these mechanisms are, you know, are they sufficient. You know, is there a lot are there a lack of mechanisms right now in place I'm not sure we saw a lot and we got a lot of good links there thank you for that so that there's a lot out there do people feel like these are lacking are they insufficient, or are we not utilizing them as the awareness, you know, a big issue. I think lack of awareness is one thing. Another thing is resource limitations because of course we saw the numbers from the emerging technology team earlier on, and we have similar numbers as well in our programs we have as well from different companies or different research organizations but of course we have limited resources so we cannot address all and we have to prioritize. Thank you Dolores yeah that's that's certainly a very serious issue and one, you know that probably is something at the policy end that that needs a push. So, they're there because in order to get it we with constraints, it becomes impossible if those constraints are are completely tying hands. Tom you look like you're ready to say something. I'm really just going to agree I think that the the numbers that we saw and also the fact that you know there are are those who have had their applications not accepted shows that there's a greater demand for that type of dialogue and engagement is available right now and that just I think to me highlights how important that is you know obviously it's great that we have it but I mean you asked could we do more I think the answer isn't in the day that there's obviously a lot of interest in in that type of engagement. Thank you Tom. I'm going to go to slide on now. Kelly poses is, I think this is. Is there a need for more direct collaboration between industry and regulators not just academics and regulators to develop understanding of capabilities. I think we've talked about that a bit but certainly open to touch on it again. I think we'll let it always go first. Well, I honestly, I've got this constantly. Most of what I do is regulating between bio industry and regulators, the regulators and I'm sure the FDA is the same extremely open. There are new systems in the UK, which we're working with the MHA together with the Americans, or the orbit project orbits is not particularly manufacturing, but the way that we discuss it is includes manufacturing. And you know I think project offices are very good example where one set of regulators communicating with another set of regulators so it's not just industry to a regulator. So in history is not interested just talking to one agency, even the FDA. It's a global aspect. I remember some years ago, we were looking at something and they said my market won't float because the FDA won't accept it. They said, we've got to get the Japanese accepting it, you're me accepting it, you accepting and the FDA. It's not just a local thing, but yes, very much. And you know we've also got to get the regulators talking to each other to make sure there aren't any gaps when they're talking to a section of industry. So say like the vaccines, we did that I think extremely well. But to some extent I think we were a bit lucky. I think those discussions were taking place few years before on things like Ebola. If we hadn't have had that we would have ended up with a big problem. For example, if I can add to this one is for example in priority medicines for a medical need and breakthrough that we have a collaboration between EMA and FDA and we hold a Warsaw back in 2018. We develop as a result, a Warsaw report, we develop some guidance in Europe we are developing some general continuing the discussions with FDA on the topic, continuing the collaboration. So, and actually this has been proven to be very valuable because obviously with the COVID vaccines there was an unmedical need. So some of the outcomes from those discussions have been used for the regulates to regulate the COVID therapeutic and vaccines. So, you know, there is a scope but as I mentioned, there are limited resources. So there are different initiatives here and there. Also, and for example, this was a case where we this we it wasn't a single company. We approach our European stakeholders FDA did the same with theirs like pharma bio. So it was like we identified topics, which we thought there was need for further discussion between regulators and between regulators and industry. And we approach stakeholders in a global manner and we say, Okay, we are having this do you want to collaborate and then there was very good collaboration between regulators and regulators and industry. So I think it is for the whole community to identify where are the gaps and make proposals reasonable proposals and then take the topic forward. Thank you. Thank you. I think I'm going to see if I can call on on john Erickson to speak up. If he's willing to come up and be spotlighted to talk about his question, which relates to this question is if tech, if platforms within a company can improve new technology with multiple companies collaborating on a common platform accelerate adoption even more. And, you know, john you might want to elaborate on that a little bit and I'm very interested in, in the extent to which we had in the polling questions, you know, on the what can industry do transparency was one of these. And, you know, I would love to get a little bit of discussion about the extent to which companies feel like their manufacturing innovative technologies are proprietary, or whether they are enabling and that they wish to have access. Well, thanks, Tim. So I, you know, I was was thinking about that I think it was the worst was talking about saying platforms can can really help there. Also, you're talking about having to prioritize because there's so many different technologies, but you know if if the industry in a, you know, in a legal way could get together and say, These are the technologies as we really want to work together on. So can we focus on those and get those over the line. And then once we've got that then we could work on on some other things now it would depend on getting everybody together and agreeing but my sense is that most people have very similar problems. And so the question is can we work on it together. I think that's the key issue because if you identify this, you come to regulators discuss with us we can see how this fit with our regulatory framework and this is the exercise I was referring to that we did within our regulatory science strategy. We have horizontal scanning activities and this is exactly what we are doing now in the context of the farmer strategy. So honestly, if you if you do this exercise and identify those technologies. We at the MA would be very happy to hear from you. And as I said, there are different platforms available. So companies, for example, our members of FPA and other organizations or even, you know, so, and I'm sure other regulatory authorities would be very happy to have this consolidated feedback from industry so that we can all work together and and smooth the path for the introduction of these technologies. And actually that point as well as the law is knows very well indeed the European Commission has had for many years, something called the innovative medicines initiative the IMI process, which was built on horizon 2020. And before that something called FP seven is going forward and another guy is now what that does and my guess is you probably have something very similar in the states side to is that we get industry together with academia together with regulators to basically raise what they call calls. The calls are basically areas like you said, john which raise things that industry and academia and indeed regulatory are interested in the European Commission put several million pounds behind each call. They come before committee I used to be on these committees. They're brought forward, you put a section of industry together with academia together as regulatory together, and they work it out together over a period of up to four years, if not longer. This has got I can't remember doors how much it is 1.2 billion euros something over the course of the horizon 2020 huge amount of money has gone into these. And we have actually sorted out a number of things. We haven't done, and I know I don't know if this is the case. We haven't seen much on the manufacturing side. We haven't seen much. It's been working more with things like problems. Things like developing new antimicrobials, things like developing patient education programs, we haven't developed it, but why can't we do that more globally. It's almost like an ICH program. We've done it locally because that's the way money works it's sort of ICH centered on global side but I am I is more European. If we'd work together with the United States it would have been quicker and better. Actually that's a very good proposal and I guess it's true that so far, the European funding has hasn't gone through towards manufacturing initiatives but it's something that is is a valuable. Tim, you're not going to talk to each other, you know, funding, regional funding agencies talk to each other and come up with a global or an international program. You might have invented something that John. All right, we'll talk some more. And Linda, very good for for letting us continue. Thank you for the permission there, because I was, I was going to ask for it and you beat me to it. Yeah, we still have some we still have a few, you know, interesting comments in the Slido in the in the q&a and so I'd love to talk for a couple minutes about both Jeanine and Paul, if either of you or both would be willing to raise your hand and be spotlighted, be great to talk about the training and workforce aspect of it and what the opportunities are there. And while there's silence I'm going to I'm going to go go back to Tom for a second, you know, because in Janine's question she she posed the COVID opportunity, you know, because the visibility of and the vulnerability I guess a supply chain, you know during the pandemic has has been been illustrated and Paul's ready to jump in I was just going to observe that you know time in your remarks you were talking about expectations for timelines. And you know how product timeline you can't really expect technology timelines to be a lot faster than product timelines. Well we've certainly seen some change in that. You know, so that ought to suggest that there's opportunity. If the cycle time over product can be, you know, 12 months or less than the cycle time of technology might also be able to be accelerated. Yeah, and maybe added to that the compelling needs of the pandemic, I think drove. You know, I'd say a little bit more willingness to explore strategies that were people reluctant to explore prior to that, like making material from stable pools for example in my area but you know so I think. Yeah, certainly as product timelines accelerate that might help enable more rapid adoption of technologies. So it looks like we might have a limit on number of spotlight so Janine you're you're up on here and Paul's got his hand raised so we'll go to him next but but you've got the floor thank you. Okay, thank you very much sorry I was taken by surprise there, but yeah the, the idea of encouraging people into the biopharma industry now I think from a number of conversations I've had at different and with recruiters as well they've noticed that there's a big interest now now by a farmer suddenly in the news that everybody's aware of what we do. And the huge benefits and I think people have changed their mindset as well that they're not so much after money they're after doing good for the society. And it seems to be that this is a really good opportunity to leverage that and really use it and try and attract more people because I think all the ideas that we're discussing here are fantastic but resources is always an issue and, there should be so many new technologies and you can't train everybody and everything. And we've got to be smart and we've got to work out how best to attract resources and retain them. I'd be really interested in your thoughts. I certainly agree with that I think you know we have to seize this moment. You know it's, it's there and the visibility is just, you know, never been like this before. Certainly when I was at Pfizer, you know, it was like an astonishing amount of attention. I think we have to do the manufacturing and supply chain aspects because we're trying to do something we've never done before, in terms of scope of the vaccine. And so people's appreciation has also gone up and you know Tom you made the remark about proactive investment, you know, and the willingness to do that I think, you know, Janine your point is really well taken that we really got to pick up on this, and, and do something with it and as a community, you know, making sure that we push and speak up and not sort of accept our humble, humble role, you know, that we might have might have felt like we're sometimes relegated to we used to joke. You know that it's like how the sausage is made and people don't want to see underneath it just wanted to work. And I think the benefit of that too if we can, if we can find a better way to integrate people from other industries which we're starting at one of the areas we're investing heavily in is digital and we're hiring a lot of people from outside of our industry and I'm constantly impressed by their, you know, knowledge and energy and challenged by their way of thinking I think they bring a perspective that's very healthy and, you know, there are many industries that do a lot of things better than we do that we can learn from. And part of the challenge the bargain there is finding a way to train them in the specifics of our industry so I think that's, that's a, I agree, Janine we have an opportunity and, and maybe we need to develop a little bit more muscle and how we, you know, integrate folks from outside of our industry and we're used to hiring people with 10 years experience in the pharma industry that's that often a criteria for requirements that hopefully we can start to move away from. Yeah, hi Janine lovely seeing you. I agree I think you know, I think what you're saying Tom's absolutely right you know even on the medical side you know, this is the first time my wife understands what I do in 25 years after the cove is a ridiculous way but she seems to understand what I'm up to now. But I think we have to specialize we have to say to engineers, there is a separate section or the nail you could work with which is really interesting which will provide expertise and things for patients which you wouldn't perhaps have got in other other areas of engineering. On the medical side, we're only just beginning to actually say to medics you know pharmaceuticals are and biotech is a really interesting area I've done you just started a course at a university explained to medical students what what we do. You know, and the same with pharmacy pharmacy knows it but they don't understand fully the manufacturing side they understand about production, you know, many years ago these to produce, you know, for specials and stuff like that, but they don't probably understand the manufacturing side is so interesting. The other thing is we don't actually combine things like we were discussing earlier. You don't produce a pharmacy school which has got inroads into the engineering school. You don't put the medical school together with aspects of some other technologies that we do. We've got biologists. I'm a fellow of the Royal Society of biology, trying to persuade biologists to take their heads up and not why just about nematodes or, or plants can be quite difficult, you know, we've got to persuade the biologists. I think, you know, there's more to what you do. You could do a lot more of what you do than just looking at nematodes and counting seashells. Now I'm being moved to my biology colleagues but you know it's difficult getting these societies to think, well, farmer is part of what you do in fact, you could imagine that we are the pinnacle of all the natural sciences, but persuading came to Oxford to think about that. You're in the dark side. That's it, mate. Forget about it. Can we give Paul the mic here for a minute. Thank you for joining Paul. Hi, Tim. Well, yeah, I think there's so much breath to this. It's kind of overwhelming and you're right. Malcolm, I don't think we can count on the academics to move quickly on this. But there's, there's just not any room in the current curriculum to add new courses or make new requirements. So, I think there is a lot of this coming down to continuing education. And I think it would be helpful, my opinion, but you get a good baseline on what, what does the current, what is the current mode of training in various organizations, whether it's industry or regulatory. Some people get trained now and what would be the preferred mode of training going forward. You know, we've learned a lot in education about how to do remote, remote learning. Right. We've also learned that it doesn't work for everybody. And that a lot of people still need hands on learning they need learning by doing. And I don't know the answer to that but that's something I think it's going to be important to address. But certainly is an opportunity to do things with remote learning and recorded videos and, you know, modular education just like we're talking about modular manufacturing. Who is the target audience and your organization. Do you want, you know, plant operators do you want R&D people do you want, you know, people are doing sales I don't know right. You want, and then what are the critical topics that they need to learn and I think there's some opportunity to to cluster those by your target audience. I don't need to learn the same thing but you know, if we were thoughtful about clustering critical topics by target audience I think we could start to develop some kind of a continuing, continuing educational modular grid. And I think it would be a great opportunity for a consortium group that represents multiple organizations to start with that as a, you know, put a line in the sand is to find the current state. Thank you. Thank you Paul. I'm going to have to hold it there so I can turn it over to Rex to do the closing I appreciate the discussion. Thank you all the speakers and panelists and participants and in this discussion I think we could go on longer but I think tomorrow to talk about, you know, where how we're going to move this forward so I really appreciate that the thought broken comments. And thanks everybody for your participation in this and Rex I'll pass it over to you. Thank you very much. I was muted. I really appreciate the lively discussion and certainly enjoyed the presentations in this sessions and the, and the preceding sessions. I have a little organizational question that Linda asked me to convey to you name there's been multiple questions about access to the recordings of this session. And the answer is that these recordings will be made available on the National Academy's website when they are ready. So, I think, you know, and this will encourage you to look at the National Academy's website which you may have never visited before. Now I did want to point also to tomorrow's program. In many ways, the three sessions we had today really intended to set the stage for a session for which will be really discussion of possible solution and action items. And we're, we really have a great set of speakers. Tom Fisher and and I'm sorry, Adam Fisher and Tom O'Connor the FDA will be leading off the session and then we have again a series of short talks from the industry sector and academia as well. And hopefully we'll, we'll end up with an interesting portfolio of potential solutions, which we hopefully will be able to win O through and come up with some conclusions and recommendations for community action in the future. So tomorrow promises to be a really interesting program and I hope you get a, you know, a good rest and a fine drink tonight and be ready tomorrow to contribute to the program. Linda, did you have any instructions for us to share beyond that. No, I think you cover it all. We'll be using the same zoom link as today. So tomorrow, if everyone can hop on at nine and invite your friends. We're hoping to be just as engaged today as today and also don't be so camera shy, we will hope to get more people talking and it is community after all, so look forward to seeing you all tomorrow. Well thank you everyone, and have a good evening and we'll look forward to seeing you all tomorrow then.