Speaker 1  0:04  
Young, hello and welcome to today's autm webinar from lab to patient guidance on the FDA approval process for university TTOs. My name is donville Young. I'm a member of autumn educate team and today's staff host. All lines have been muted to ensure high quality audio, and today's session is being recorded. If you have a question for the presenters, we encourage you to use the chat feature on your zoom toolbar. Should you need closed captioning during today's session, the Zoom live transcript feature is turned on and available on your toolbar before we begin, I would like to acknowledge and thank Autumn's online professional development sponsor. Marshall Gerstein, we appreciate your ongoing support. I would now like to introduce today's session moderator, Karthik Gopalakrishnan, thank you, Karthik,

Speaker 2  0:57  
thanks. Thanks, Danville, I appreciate that. Hello, all. I'm Karthik Gopalakrishnan. I'm the director of licensing and new ventures at the University of Alabama at Birmingham. So I'm going to be introducing the the panelists that we have for the webinar today, and I'd like a couple of things to point out to the audience. The first is that I have a plan set of questions that I will be asking of the of the panelists after Dr namanja Pampas provides a high level overview of the FDA regulatory approval pathways, and also be monitoring the chat box for additional questions. However, we won't be able to get through all the questions you all have, so if there are specific questions that have not already been asked and answered, please do write your question along with your email and put it in the chat box. And a couple of the panelists have agreed to look at those and respond to you directly with that note. Let's quickly introduce the panelists. So I'll start with Dr Beverly Laurel. She is a senior medical and policy advisor on King of Spalding FDA and life sciences team. She was previously professor at of medicine at Harvard, and served on ni study sections and on FDA Cardiovascular and Renal drug advisory companies. Prior to joining King and Spaulding, she was the global chief medical and Science Officer for guidance. Dr namanja Bumpus serves as a strategic advisor on regulatory science and policy. She was previously the at the FDA, and served at the FDA from 2022 to 24 as chief scientist and then as FDA Principal Deputy Commissioner. Before joining FDA, she was on faculty at Johns Hopkins, where she was a professor and chair of the Department of Pharmacology and molecular Sciences. Dr Mike Ehlers as an entrepreneur partner at NPM bio impact, a leading Life Sciences fund. Previously, Mike was the Executive Vice President for Research and Development at Biogen, and helped get six drugs approved in neurology and rare diseases before joining his industry career, he was an investigator at of the hsmi at Duke University. And finally, Dr Christina Young is a technical advisor on the innovation protection and IP team at King and Spaulding her backgrounds in chemistry, applied physics and electrical engineering, and she has spent more than half a decade at the FDA as a reviewer and to provide technical expertise on all aspects of patent litigation and FDA matters and consultation on site at client manufacturing facilities for FDA inspection preparation. And with that, I'm going to request Dr Pampas to provide us with a high level overview of the FDA regulatory pathway magic. Over to you. Thank

Speaker 3  3:42  
you for that intro, and I'm really glad to be here with you and talk some of this through. So FDA is comprised of a number of centers that cover the range of what FDA regulates. So I'm here. We'll focus on medical products, human medical products, specifically because there is a Center for Veterinary Medicine, but here we're talking about cedar, the Center for Drug Evaluation and Research, the Center for Devices and Radiological Health, CDRH, and the Center for Biologics Evaluation and Research. There's also human foods program for food products, cosmetics, personal care products are regulated separately as well, and there's tobacco. So these are really the human medical products that we're discussing. And essentially each of these centers have products that they specifically regulate, and the way that they do so comes to them through individual statutory authorities that they have. They all also have science programs, and they work to advance regulatory science in addition to their overall review functions, and often partner with academia and industry, for instance, through collaborative research agreements and things of those nature as well. Go to the next slide. So. So first we can talk about cedar, the Center for Drug Evaluation and Research. So cedar is the largest Center at FDA, I think, all told, including, you know, contractors, fellows, all the staff. It's usually about five to 6000 people. And so they regulate anything that would be defined as a drug, essentially. So the definition of a drug that FDA uses, again, these are kind of defined in the statute. So it's an article intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in humans or other animals. But cedar specifically works on humans. I mentioned there's another center, CDM, for animal drugs, and these articles, other than food, are intended to affect the structure or function of any part of the body. So in thinking about, for instance, a drug or even what's an active ingredient, it can be something that just impacts, say, cellular function, and that would be considered an active ingredient. And I think interestingly, there are things that are considered drugs that people may not realize. So for instance, if it's toothpaste, if it's toothpaste with no fluoride, it's just, you know, regular old toothpaste, then it would be regulated by FDA as a cosmetic. There's no personal care product definition under the Food, Drug and cosmetics act, it's cosmetics. They're called. So the toothpaste without fluoride would be a cosmetic. Once you add fluoride, it becomes a drug, because then it has a function. So things like toothpaste, Antiperspirant Deodorant are also drugs, in addition to things we think about like a heart medication. So cedar has a really broad mandate, and on the slide you see the additional aspects of the definition. So next slide, thank you. So the process for approval of a new drug, and so here we're really outlining the approval process for a drug that would be, for instance, like a prescription drug. So a drug would be over the counter actually has a different pathway it can go through, which is called the OTC monograph pathway that's much more streamlined and happy to talk about that anyone has questions or wants to follow up on that later. So something that we think of, though, as you know, someone go to the pharmacy and get is going to go through this kind of more substantial process. And so it really begins with the preclinical development space. And you know, I was a professor at Hopkins and chairing the pharmacology department. We had lots of activity in this space. So I know that universities this is a really active area. And so essentially, the preclinical development is that identification of a target for specific disease, and then the preclinical studies, and that usually includes animal testing or use of complementary in vitro systems to understand things like potential toxicity from the drug, both acute and chronic, and say preclinical species looking at, is It carcinogenic? Is it teratogenic? Is it mutagenic? Pharmacokinetic behavior, so looking at metabolism and absorption, excretion, also identification of formulation, and based on those data, what initial dose could be used in human testing and good laboratory practices used in this process. So this is really kind of bringing together that laboratory component. I will say, increasingly, people are using AI to augment some of this. It's not yet replacing any of these tests, like replacing an animal test, for instance, but it is being used increasingly to augment there. So that's another area for innovation that I think universities can help really drive. In addition, you may hear there's discussion around using new approach methodologies. They're called or alternative methods to animal testing. And so a lot of that you're seeing now, things like spheroids and organ on a chip, 3d cultures coming in as well to help augment some of this testing that's being done. And I think that's another area where universities can really help spur innovation. Additionally, you know, at this process, you're really looking at, what would the manufacturing specifications be, and what would the manufacturing reproducibility be? Ultimately, thinking about manufacturing, especially in the case of biologics, there's a lot of testing that's done as well that covers some of this, really trying to understand, are there contaminants and things like that that could affect the final product? So the manufacturing step is really important, and there's a lot of experimentation that goes on as part of that. Go to the next slide.

Speaker 3  9:41  
So once you move past that pre clinical development phase, there's then you know the clinical phase, if all goes well, the pre clinical development and you have a good understanding of what a dose could be in humans. And you know this, it seems that this is a drug that could be safe and have efficacy and be beneficial. People. So there are a few phases of clinical studies would be done. So the first would be phase one, and that's usually a smaller population, often in the dozens. It could, of course, be, you know, 100 people or 200 people, but often in the dozens of participants. And there you're looking for safety signals, but at PK and dose finding. And so you'll do this usually in healthy volunteers, but can also be done in people with the actual disease, if it's a drug with where the patients are high risk. And in phase two, the next step would be that you have much larger cohorts. So this is where you're looking, really in the hundreds, and you're looking at efficacy now, and also trying to understand what some of the side effects might be, and more understanding of dose. And then finally, get to phase three, which is where you're doing a much larger trial. It could be 1000s of people. And these are usually, usually randomized control trials, even though there are instances now of you know synthetic arms and using kind of historical data and things like that. So there are some innovations happening there, but usually randomized control trials that can be really used to confirm the safety and efficacy. Rare diseases are treated differently, just because they can often be far fewer patients. So with rare disease, there's not only potentially a much smaller group of patient patients you're looking at, but you might, for instance, also be including information about the natural history of disease, as you're doing kind of design and analysis and here, using good clinical practices and informed consent, all of the an IRB review, all of things under the umbrella of human subjects, protection and public disclosure, disclosure on clinical trials.gov, so in the review process, there are kind of lots of things that reviewers are going to be looking for. So at that initial preclinical stage, when you're bringing them data for an IND and investigational new drug, you know that's going to have all of your animal data in there, or in vitro data, whatever's been done pre clinically, to show that the drug is safe and efficacious, or has is reasonably safe and you reasonably would be efficacious, potentially. But safety is really a focus there, of course, and additionally, as we mentioned, those manufacturing things you're looking at once you move forward to through the clinical phase, then they're reviewing a new drug application, and they're going to issue an action letter. And essentially, what they're looking at this new drug application, and it's a multidisciplinary team that is going to have pharmacologists and chemists and clinicians who are specialists in certain areas, and statisticians and microbiologists lots of people, and they're also policy professionals that will weigh in on certain aspects as well. So it's a very collaborative process, and they're going to be basically analyzing study data, and do they agree with the conclusions? And, you know, does this really seem that something that would be beneficial? And so they're going to make some determination there. There also may be an advisory committee meeting that's called, and that's something that can be useful as well. With the FDA getting feedback to people, from people outside of the FDA. Those committees don't make the decision. They make kind of recommendation FDA and give feedback. FDA makes the final decision, but incorporating, of course, advisory committee feedback. If an advisory committee has been called, you can go to the next slide. So then you know, there's post approval and marketing. So if things have continued through all of those phases, the FDA may mandate post approval studies as a condition of approval. There also will be monitoring of safety issues after drugs are on the market, the sponsor is required to submit periodic safety updates to FDA. And there also is a system that facilitates reporting of adverse events by consumers and physicians. It's called Med Watch. And there also may be other requirements around safety information and ways that labeling might be impacted, or ways that information needs to be disseminated to patients. So it's kind of an ongoing monitoring discussion, post marketing and the next slide. So as mentioned, these are kind of the different phases where all of those things fit. And so that ind phase we've talked about it, really looking at safety. And is this something that could be safely used in human clinical trials? And there are many components of it, and that's going to include not just that kind of animal testing data initially was mentioned things around manufacturing. Capturing as well, and there will be specific kind of forms and things you have to give to FDA. There is an opportunity here, even before this step, to meet with FDA, to discuss plans, what you're planning, to put in this application, and get feedback from them there. And also at this step, it's another opportunity to have discussion and feedback with FDA as well as you proceed into the next phase, if you're allowed to proceed with that from filing the IND. So this is a great communication step with FDA, but communication can even happen before and go to the next slide. So the NDA, as we discussed, you move through the IND, they say you can go ahead and do clinical studies. If the IND they feel is not sufficient, then they'll say that you cannot start clinical studies, but the IND is efficient, you can move on to clinical studies. Have those phases, as we discussed, and then your new drug application will have all the components that really reflect those studies that you did, in addition, again, to manufacturing and other evidence, they really need to show that the drug is safe for use and that there's substantial evidence that will have the effect that you report it to have. And there's also things like patent information and labeling also that is included in this package and that you would be discussing with FDA as well and getting feedback on and so then we can go steps. So there's that review of all of the information in the NDA by FDA, if you use the NDA pathway, as I mentioned, and then you go to FDA approval. So here we're laying out some pathways, again for an OTC drug. There's another pathway called the OTC monograph pathway. So many drugs that you see over the counter can go through an NDA, but often, you know, they do not, if it's, for instance, you know, a drug containing kind of the standard over the counter dose of, you know, acetaminophen or aspirin, that's going to be through the OTC monograph pathway, likely, even though they can do an NDA. So here we're focusing very specifically on these drugs, except that you'd be thinking of more as behind the counter type drugs. So there's called the 505 b1 application, the 505 b2 so the 505 b1 is really kind of big package. Classic new drug, 505 b2 is often something that may already be approved, but you're trying to make some change, like, say it's an extended release form, or you want to change formulation so A, 505 b2 you can rely on data and information that's pre existing, where the 505 b1, you're usually generating all of the data, kind of de novo for the application. There's also the abbreviated new drug application for generic drugs. And there's a new pathway that you know should just now be taking effect that is kind of in between where I mentioned that over the counter and this, and that's called the active pathway. It's additional conditions of non prescription use. And essentially there it's a bit of a hybrid, where you can have something over the counter, but maybe it's it takes more understanding and more kind of involvement to actually use that medication. So in that instance, there will be kind of a pathway you can use to get the proofs. The idea being, maybe drugs, say, for chronic disease, could become over the counter with this additional condition. So there is some development and innovation, I guess what I'm trying to say around some of these classical pathways to allow for greater patient as access to various types of drugs. So we can go to the next slide. So, so that was cedar, the Center for Drugs. Now talk about devices and CDRH, the Center for Devices and Radiological Health. So just like for drugs, medical devices have a very specific definition. So you know, it's intended for diagnosis, cure, mitigation, treatment or prevention of disease in humans, or intended to affect the structure or function of the human body, and which does not achieve its primary intended purposes through chemical action. So it's really a device. It's not a drug you can go to the next

Speaker 3  19:20  
so there's an intended use, so it refers to basically the general purpose of the device or its function, and then indications for use. So you know, what's the indication a disease or condition the device will diagnose, treat, prevent or cure, just like with drugs, and kind of this broad range I mentioned of what's considered a drug. Similarly, devices, there's a broad range, so something like a toothbrush or a hospital bed is a medical device. But then on the other end, of course, you have things like pacemakers that we would or ventilators that we would usually think of some medical device. So it's a broad term, like said, it includes things like tooth. Questions. Okay, keep going. So with that, there's this classification of medical devices, class one, class two, class three, and you see kind of increasing risk as that class gets higher. So class one or more, some of the things I mentioned, like toothbrush or hospital bed, class two could be something potentially like a syringe, and then class three would be more of the pacemaker. So it really, you know, kind of dictates the level of kind of interaction with FDA and regulation that's required to get something on the market. Keep going. All right. So there are four major pathways, and we'll go through each one of them, so we can just go to the next slide. So the exempt devices. So 501, K, exempt devices. So these devices are exempt from free market notification, so they're not going through an approval, essentially, or any clearance with FDA, they're exempt if it has the advice has two characteristics, and essentially, one, it must have the same intended use as other legally marketed devices and a generic class, and the device must operate using the same fundamental technology as the other legally marketed devices. And this is self determined by the company, but the FDA does have the right to override override. So there are certain devices, lower risk, devices that fall in this group. And if they meet all of these requirements, and there's guidance outlining this for companies to follow, then the device can be marketed. So they're exempt from pre market notification to FDA. Okay, next one, there's a pre market notification 510 k. And so a 510 k is a device that is substantially equivalent to essentially a benchmark device, a predicate device. And FDA clears, we say clears not approved 510 k devices if FDA makes a finding of substantial equivalents to a predicate device. So their predicate device would be something that's legally marketed as a class one or class two device. Already they are devices that have also received 510, clearance. Mostly, they may also have been, we'll talk about another de novo process. They may have been cleared through that pathway or classified through that pathway. And they are devices for which FDA is not called for pre market approval. So this is a pathway for clearance. So it's kind of less than what you'll see when the pre market approval pathway that we'll discuss. So we can go to the next thing. So the pre market notification of 510, K, so essentially, again, showing substantially equivalent that it has the same intended use as the predicate device, that it uses the same technology, or that it has the same intended use different technological characteristics, but the differences don't raise questions about safety or effectiveness. So essentially, it's showing that it's substantially equivalent, based on these metrics, to something that's already out there. All right, keep going. The de novo classification is a bit different. So the FDA can grant a request for de novo classification if they find that there's a product that has no predicate, it's not a type of product that's been previously approved as class three, which was that higher risk group in an existing pre marketing approval application, and it meets criteria for classifications lower or moderate risk, but class one or class two. So the double classification, if there's something that you know doesn't it has no predicate, something different, but it fits these other criteria, a company can either make a request for this classification, or it can happen at the time that FDA reviews and finds, you know that there's no predicate device, and then that determination we made. But most often, companies are applying for that de novo classification, and if it's granted by FDA, they can move forward with marketing of the product. And then the last for devices is the pre market approval. And so this is the most involved of these, and it's an application for the proposed intended use on technology based on the termination that the pre market approval application contains sufficient valid scientific evidence to assure the device is safe and effective for effective for uses. So there are clinical studies involved which was different than what we looked off or other devices clinical studies showing safety and effectiveness. There may be studies specifically showing that it can be used easily by people that if they need to use the device outside. Of, for instance, a healthcare facility. And there also is involvement with FDA inspecting the facility, et cetera, so, and it also can go to advisory committee. So this is more of a full application, essentially, to get a device approved that includes clinical studies. And we can go on and so examples of those higher risk class three, I mentioned pacemakers. And then there are other examples, like defibrillators, okay? And then our last center we'll talk about is CBER. And so CBER regulates biologics. And so biologics are vaccines are approved through CBER blood, blood components, therapeutic serum. So essentially, things that we would think of as biologics, monoclonal antibodies, are through cedar, the Center for Drugs. But most of the other things that you might think of that come to mind is biologics are going to be CBER. But we'll break that down a little bit. Okay, next slide. So again, vaccines, blood and blood components, human tissue and cellular products, gene therapies, cell based therapies, are all going to be regulated through CBER. Keep going. So is there a biological drug? So that's a question. So I told you sometimes it's sometimes there's this question, is it a cosmetic or a drug? And there's also this question, is it biological or drugs? So cedar, the NDA pathway we discussed, are going to be things like therapeutic proteins, like insulin monoclonal antibodies, immunomodulators, CBER, gene therapy, cell based therapies, vaccines. Are going to be CBER, the regulation of them is different. Instead of an NDA, like with cedar, with CBER, it's going to be a biologics license application that would be filed. But there are many similarities and components, as far as clinical trials and all of those things keep going. So I think that that's my part is done now. So happy to answer any questions, and

Speaker 2  27:06  
that's the end of the formal kind of overview. So thank you so much for providing it that is really useful and helpful to kind of tackle these questions, and if I might maybe call on Bev to answer the first question that I had prepared, how do we even know for sure that a product is likely to require approval by the FDA? Because there are so many different pathways that namaj talked about. There's Python k There's PMA, there's other agencies, cbirt cedar, regulate other things for drugs and biologics. But how does a person who's trying to bring something to market know that it's required, but if you to prove something, well,

Speaker 4  27:51  
that's a great question. I think probably the first step for the entrepreneur is to ask the question, are there somewhat similar products on the market right now? And if so, how are they regulated? And how similar is my innovation to those? I think a second step, but you can see this is complicated. Is looking at the definition, because you saw that a device can be an entity that's used for treatment or diagnosis, and so can a drug. So I think the third step, and I'll tell you a resource I think, is very helpful, is, if you are not certain, after you've done some pretty rigorous diligence, it is possible to reach out directly to FDA for a meeting, where the intent would be that you would actually have a formal meeting with FDA, have a presentation of what your product is composed of what it's intended to do, and to get a determination. A very good resource that actually was published just today is FDA just issued a final guidance document that talks about the panoply of potential meetings with FDA, and how one reaches out to FDA to arrange to have such a meeting. And I think that that is a very good starting point just published today, and it's worth it for all entrepreneurs that are listening to this, I think to look at that and download it

Speaker 2  29:48  
that is super helpful, if I might ask a follow on question. So you said entrepreneurs can reach out to the FDA, and the audience here is not entrepreneurs, but tech transfer offices and. Personnel within and I don't know if we necessarily have the bandwidth of the time to do that, but is it possible, as owners of the technology, the universities, can the universities approach the FDA to get this guidance on whether a product needs FDA approval or not?

Speaker 4  30:18  
Yes, I think that is not the most frequent entity that is asking for those meetings, but I think it could be done, and it would probably be most effective to do that in collaboration, essentially, with the scientist or physician, if you will, inventor, got it. Thank

Speaker 2  30:42  
you. So let me bring Mike onto this discussion. So, So Mike, from your VC perspective, how do VCs look at technologies whose commercialization will require FDA review? Are you more inclined, less inclined to kind of work with those technologies?

Unknown Speaker  31:01  
Yeah, no. Thanks. Thanks for the question and and for the Monge his overview, which is excellent. I mean, there are a lot of things is sitting in VCs that are looking at technologies and considering you know what will be required in terms of regulatory review for commercialization, you've heard some of them. A first category that's important is regulatory pathway clarity. Is there a well established FDA pathway? You've heard about several of them here today, 505 B, twos, PMAs, NDAs, etc. Have similar products been approved? What was their timeline and cost? Does the FDA view this an indication or product class is addressing a significant unmet medical need, and those kind of those clear, precedented path de risks the investment by reducing timeline and and approval uncertainty. A second way that VCs look at technologies and potential FDA review is the time and cost to approval, how much capital is needed to reach pivotal data or FDA submission. Can the company or entity unlock value at discrete FDA related milestones like ind filing or end of phase two meetings or submissions? And that's important because longer, more expensive development timelines require more capital and and obviously reduce the internal rate of return considerations. A third important area that that that we think about on the venture capital side is clinical and regulatory execution risk, which is has the team that's part of this brought similar products through the FDA before, has the company already had pre ind or pre submission meetings that Bev was just referring to? How did the FDA respond? Is the proposed trial or testing or clinical development plan statistically powered and aligned with FDA expectations? Is there a knowledge on how to do it and and this matters, because execution failures or regulatory setbacks can can significantly delay or sink companies or entities that are that are created to pursue these technologies. And then another important one, of course, is market opportunity and reimbursement. I mean, it's the post approval market large. Is it accessible? Will insurers reimburse? Do providers have incentives to adopt? Are there other companies approaching the FDA or other regulators for similar solutions and and and that's an important consideration, I think, for VCs, because even with FDA approval, poor commercial uptake can can limit a return on investment. And then finally, I think one, one area that we in the venture capital space look at for for technologies whose commercialization might require FDA review. Is exit strategy alignment, which is to say, Are there strategic acquirers who value FDA cleared or approved assets, depending on what we're talking about, and can an can a company or an entity here IPO pre revenue, if clinical data is strong and that's important, because obviously, from investor perspective, there's a need to plan for timing of exit pre, or that's often pre or shortly post approval, depending on what you're doing, especially in capital intensive sectors like biotech or med Tech, which is what we're largely talking about here,

Speaker 2  34:43  
that is super awesome. Thank you so much, Mike. So another question that I had was, how can we leverage a regulatory expertise to improve our chances of approval? Is it always advisable to go through a regulatory expert? And I'd like maybe Christina. And Manji to kind of touch on these topics. Christina first, maybe

Unknown Speaker  35:04  
Sure absolutely, you know to answer your first question, how can we leverage regulatory expertise? One way you can do that is by looking for FDA experts that have real world experience, who have actually been at the agency because they can provide you know expertise from experience to help you understand the process and requirements at every step. Another area where you can leverage regulatory expertise is how to engage with the FDA, whether it's preparing in advance for a meeting. For example, there's certain techniques and ways to ask questions in a meeting package to get responses from the FDA that are actually responsive to your questions. And that part's important, and also, you know you want the feedback and buy in from FDA, so working with a regulatory expert can help you do that as well. Another part of the process is how to respond to FDA when it comes to action letters, right, and preparing in advance for applications inspections during the scientific review stage, right? So all of this advice can come from you know, regulatory experts that have real experience at the FDA doing so yeah. And lastly, helping the FDA understand your innovation is critically important, right? In my experience, oftentimes, stakeholders in FDA may speak two different languages, right communicating with FDA, and quote, unquote, FDA speak, for example, can really help the agency understand your innovation and the science behind your innovation, to help the agency make better informed decisions, and it can also streamline the process for you as well, and it can save, you know, time and money. Yeah, so that would be my advice for how to leverage regulatory expertise. Namanjay, did you have any tips on that as well? I agree

Speaker 3  37:14  
with that 100% and there was so much of that that I was going to say, and I think that that's great advice. There certainly can be some communication with Fauci through a letter, for instance, that there's a little bit of reading the tea leaves that can be useful. Just you know what was fully meant there, just making sure that you really understand. And having someone that was mentioned that has that experience can help with. Know, this is exactly what is being said, and this is, you know, an effective way to address it. I think also people should feel, you know, you can reach out to FDA, communicate with FDA. I think people sometimes feel nervous that they should only communicate when they think everything's tied up nicely in a bow, but actually having those conversations earlier on in planning phases can really be useful in streamlining a lot of you know, from an academic perspective, I think there's a lot of discovery that happens, and it's really exciting science, but it doesn't always readily translate to something that could become a product and really proceed through the regulatory process. So, the earlier that PIs or even maybe universities have people on call that can engage with their you know, investigators around the development phase, I think the earlier you can bring in that regulatory expertise, the better the chances are, just because you can really mold and shape your program and your strategy. And I think people often think you've got to be like, ready for clinical trials before you start talking to a regulatory consultant or, you know, talking to someone with expertise. But I say it's actually very early to help make sure that you're proceeding as efficiently as you can and have the best chance of making it

Speaker 2  38:57  
through. So if I might ask you a follow on question. So Bev touched on this new guidance that came online today. So the follow on question was, are there resources within the FDA that we can leverage? Clearly, there are. Do you want to add something more to what Bev alluded to?

Speaker 3  39:16  
So there's a lot of information, if you go to FDA website, and a lot of their guidance documents around many of these things, as far as crafting certain parts of applications, what they're looking for. And I was just brushing up the other day on one around cell based therapies and some of the testing done around manufacturing. So there are a lot of guidance documents that are on the FDA website that you can find, and you can find them by center or by topic, and use a search engine to find them, and they have a lot of detailed information. It's very useful in helping to bring you where you need to go. So I would say, engage with the FBA guidance documents. That helps a lot, too.

Unknown Speaker  39:57  
100% agree with naman Jay and I. I'm just adding to that, there's also small business and industry assistance as well, and they provide direct communication service. They have a phone number you can call. They have regulatory references and training resources online as well. So that can also be beneficial. In addition to the guidance is for industry that namanjay mentioned, I

Speaker 4  40:23  
think there's one more resource. And this is not something that is a blanket resource for all innovations, but there can be innovations that are in a sector that is somewhat controversial, publicly and at FDA as to how to regulate that. And in many instances, when that occurs, there may be an FDA advisory committee that is not focused on a specific product, but it's focused on a specific type of drug or biologic or device. And if that is potentially pertinent, those are very, very important meetings to follow, to download the transcript and to try and understand what was really being said here. And it's it's a little bit of the way of reading the tea leaves and understanding what is FDA concerned about? Why did they spend the resources to have this very costly public meeting? And I think that's not applicable to all innovations in new drugs, devices or biologics, but there are some that it's very important for.

Speaker 2  41:42  
Thank you. That's helpful. So let me switch tack a little bit. And if you read the newspaper or any online resources, there is a little bit of uncertainty that seems to be evident from the pharma industry perspective and regulation by the FDA. So, so what I asked Mike this question, how should we think about technology and product development outside of the US? Can ex us development facilitate the FDA regulatory pathway in the US?

Unknown Speaker  42:18  
Yeah, it's a great question. I know we've been focusing on the US and FDA and but of course, innovation is global. Markets are global, and different markets differently. So I think it is quite important for university, tech, transfer offices, inventors, entrepreneurs, to really contemplate technology and product development outside of the US, and that can be a very important consideration. So I think there are a few strategic drivers for ex us development to consider. You know that market pull exists abroad. Some innovations may address stronger unmet needs or regulatory incentives outside the US certain circumstances, many cases, development costs are lower early stage clinical development or others can be, maybe significantly cheaper in other places to to facilitate capital efficient development of a product to the market. You can have a faster time to data in certain circumstances. Countries with streamline pathways can enable earlier generation of proof of concept or clinical validation data in certain instances and and I think we're seeing this dramatically increasingly in the last two years. By the way, I'd say the rise of China as a critical market, both for accessing assets, but also for aspects of early clinical development in certain spaces. Then of course, there's the whole global commercial potential. Licensing or partnering abroad can help capture value, even if a US path is is uncertain or or delayed. So I think those are key strategic drivers. There's another element that I think is quite important, and it might segue to some comments from nemaji or Bev or Christina, which is you need to ask yourself, can ex US data help us regulatory pathways? And I would say the core answer that is yes, but with important caveats, the FDA may accept foreign clinical studies not conducted under an IND to support an IND or NDA submissions or bla submissions, if they're well designed, if they're performed by qualified investigators, if they're conducted under GCP standards, etc. And that can be important. Sometimes there are things where they're bridging studies that. Can be required for combination products or other things where ex us studies might require bridging studies in US populations. It's something to think about. And the device space, I know there's often consideration of obtaining a CE mark first. So for med tech and digital health, often explore the EU for earlier CE marking that may that can inform us submissions. So in considering this though, I do think there are important things for tech transfer offices to manage in terms of risk, which is IP enforcement and ownership, ex us development can raise issues in patent strategy. FTO enforcement capabilities you need to ensure international filings. I can't even count the number of times I've seen dramatic strategic errors in the global or nature or lack thereof, of of patent filings, for example. And of course, different jurisdictions, different markets operate differently. So there's you need to manage the risk of regulatory differences or divergences, and you typically want to ensure that x US data collection still aligns with any future FDA expectations, especially for things like pivotal data. So best practices there early FDA engagement in and around that topic to determine, for example, if foreign data will be acceptable, making sure you can have a structured global development strategy. You know, don't just think about the US. And then another important thing is partner vetting, which is using the right types of if it's CROs or partners or collaborators with a clear regulatory track records, and GCP compliance if you're going ex us. So I would say it just in conclusion there it can be a important strategic level lever for advancing technologies to commercialization, especially for de risking novel technologies. And if done right, it can accelerate value creation and even support the FDA path.

Speaker 2  47:13  
Oh, that is fascinating. The man, did you want to comment on that and actually have a follow on question for you? Mike mentioned something interesting, that even if you have ex vivo trials and things that let's, let's take a drug as an example, you can ask the FDA for guidance as to how best to do that. But how does the FDA look at it from the inside? I mean, is it a not tested here syndrome, or is it actually collaborative and supported?

Speaker 3  47:46  
So, yeah, so there's a lot there. There's a lot of interaction between FDA and other regulatory agencies. I mean, when I was there, I met with my counterparts all over the world at various times, review divisions have discussions and collaborations and things those nature. The Oncology Center of Excellence specifically has been very forward leaning in kind of global thinking, more globally about collaboration and how you do those things. So there is a lot of interaction. I do agree it is really important to, you know, think about the entire world, of course, for products, and to be sure, as part of that, that you are discussing with FDA, just so that you're developing in a way that you're not having to kind of do things so differently, different places, there are ways to coordinate much of it. As far as clinical trials, you can see there's guidance and other communications from FDA around that. I mean, there is a real interest in ensuring that clinical studies are representative of US population. So that's something to consider. But of course, we know that this is a global enterprise biomedicine. But one thing that came up that the term combination drug, I think, was used, and I had been while I was presenting, wanting to say something about it, and I forgot. I kept saying, What did I forget? So it's combination drug. What I wanted to say is use that as an example of why it's important to have FDA expertise involved early on. So if someone is developing or seeking develop a combination drug to treat something, and they're doing all their clinical or pre clinical studies in that combination, and then they're writing up their clinical plans combination. Actually, there's a regulation in the Code of Federal federal regulations that says that in most instances, and it gives some exceptions, but in most instances, you need to understand a combination drug, the components individually, and how safe they're individually. So you have to do studies with monotherapies. You might have to do a clinical study of the separate mono therapies, not just the combo. You don't want to go too far down the road without knowing things like that. So there's lots there's lots of nuance and just things to understand that will make things better for you, and that that might be different than what another. Regulatory agency in another part of the world might say or need so having discussions early and having that FDA expertise as close to as possible early on is really useful in ensuring you can move your program forward and get things to patients that might be really useful for them.

Speaker 4  50:16  
Now I'd love to ask you a quick question going back on the Oh, US versus us. One of the things that we see people struggling with right now is there's a law that's still an active law that called for diversity action plans. And this was not just sort of dei for diversity sake, but the notion was that you would target your clinical trial population based on what was representative in your target population, in terms of sex, Gender, race, ethnicity, and fundamental to that in the background was the notion that these studies and clinical trials would be representative of what the practice of medicine was in the US. Where do Where do you think we sort of stand on that today?

Speaker 3  51:22  
Yeah, well, I think that science is served when we understand the full range of potential biological response, or as close to full range as we can, and that you get that by, you know, thinking about the broadness of, you know, the population in the world. So it's important. It's really a scientific imperative for understanding biology. I think that right now, it's up to kind of, you know, people doing the development to think about how they can embed those principles to really be able to see if there's going to be some sort of toxicity related to some genetic variant that you might be more likely to see in a certain population, for example. So it really lies there. As far as where those plans might go, we just don't know. We know that obviously the guidance is not, you know, finalized, so it's hard to predict what's going to happen with it, but I think that the developers can think about, you know, from a scientific standpoint, how can they strengthen it? And that, embedding it, embedding those principles early on of thinking about the total population and representation and certainly can help, you know, make things stronger there. But as far as FDA, it's just we don't know where it's going to go. Thanks.

Unknown Speaker  52:40  
That's helpful. I just wanted to add one note that just will might seem like it deviates a little bit, but if we're talking about global testing, right, testing in other countries, we also have ISO standards, right? And FDA, you know, they participate on these ISO standards on behalf of the United States, and so does a good portion of the world, right? And so if you're doing your testing in another country to support FDA application, you can rely on ISO standards, and a lot of times that might be incorporated into the regulations anyway, and FDA has buy in and input on those ISO standards and their global consensus standards that might give more confidence into the way you approach testing. Thanks,

Speaker 2  53:28  
Christina, so I may have one more question for Bev and Amanda, but really I want to expand this to everybody. It's the two part question. So what steps should universities or their spin outs take to prepare before starting the regulatory process, when and how to start? And really, if there was one piece of valuable advice you would give to university to use for navigating the FDA approval process, what would that be? So I'm going to start with Mike, and then, as it's showing on the screen, work my way upwards to namanji. So Mike,

Unknown Speaker  54:03  
I would briefly say, involve regulatory consultants early, require licensees to present a credible regulatory strategy and diligence or milestones.

Unknown Speaker  54:14  
Okay? Christina,

Unknown Speaker  54:19  
yeah. I mean, my response is very similar to what no one Jay said earlier, and I think it's really helpful be proactive in your engagement with FDA, they want to help, and there's a, you know, there's a number of mechanisms to do that, but submitting a meeting package and get involved early. They really do want to help, and don't hesitate to meet with them, ask them questions like we plan to do X, how does this fulfill FDA requirements for y? And seek their feedback and advice before you spend extensive time and resources allocated that is, you know it's not fit for purpose or doesn't meet FDA requirements.

Unknown Speaker  55:01  
Beth. Anything to add to that?

Speaker 4  55:02  
Yeah, I think those are great comments. I think something very fundamental for your innovation is basically making getting two senses of judgment very early. One, is this a product that is, in fact, regulated by FDA, if it's a product that's intended to sort of augment healthy practices in everyday life, or to just simply to monitor the number of steps you're taking. That may not be regulated by FDA at all, but making a judgment and getting feedback, is this regulated and then trying to understand and make very good judgment, is this going to be regulated as a drug, as a device, or as a biologic? And I think those are very critical early steps

Unknown Speaker  56:00  
namanja, anything else to add to that,

Speaker 3  56:02  
I'm agreeing with all of it. I just reiterate having a go to person or a couple of people who have that FDA experience. There are many folks out there consulting on FDA. I think if you can, you know, bring one person who maybe was a reviewer, whatever it is, into your team that's great. Or just have someone that you can phone up anytime and really encouraging the scientists you know, the researchers doing the work to talk to those folks early, so that you always have the regulatory components in mind as you're doing even the early on experiments. You do not need to wait until you feel that we can go to the clinic with this potentially, the earlier the better.

Speaker 2  56:47  
Got it. With that note, I kind of gone through the chat, and I don't think there are any questions there that we have not already covered. So I'd like to really thank the panelists for their time and their expertise that they provided to our audience. Super helpful. And with that again, thank you so much.

Speaker 1  57:12  
On behalf of autumn, I would like to thank our panelists for the informative presentation today, and thank you again to our online sponsor, Marshall Gerstein, a recording of this webinar will be available for viewing in the autumn Learning Center within a week of this event, and is included in your registration. Please be sure to complete the webinar evaluation, which will open immediately when you sign off this session. And thank you to everyone for being a part of today's presentation. Have a great afternoon, everyone. Thank you.

Transcribed by https://otter.ai