Transcription: Development Challenges for Cell Therapy Products Expert Panel Discussion – Live Free Webcast

The following transcription is taken from The Windshire Group’s webcast Development Challenges for Cell Therapy Expert Panel Discussion”:

Terri Melvin: Welcome everyone to today’s Webinar, Development Challenges for Cell Therapy Products Expert Panel Discussion. I’m Terri Melvin, and I will be today’s moderator. We have with us today three expert panelists. Panelists will first tell us a little bit about themselves, then address some talking points in their particular areas of expertise. Then we will dive into your questions live. That’s my favorite part. I will now turn it over to our first panelist, Dr. James Blackwell.

James Blackwell, Ph.D., M.B.A.: Thanks Terri. Thanks to everyone in our audience for joining us. I’m president, principal consultant for The Windshire Group. Our hope today is to make a new industry, friends and acquaintances. We also intend to serve as an information resource for organizations by providing answers to some of your most pressing questions around this very important and timely topic. Please don’t ask any confidential information. We don’t market in it, and we’re not responsible for any of the advice or opinions that we offer today. So, after self-introductions, we will share a few of our personal thoughts about cell therapy and then we will get started with the questions. I will then close our expert panel webinar with some concluding thoughts.

Prior to becoming a consultant, I held several senior technical positions within the industry, in area of development and production manufacturing. I’ve been an industry consultant now for over 12 years, assisting with CMC aspects of quality products in all major classes including cell therapy, which has been a growing area for us, and throughout the product life cycle from very early development through commercial issues and problems. So, I’d like to now turn it over to Dr. Hanley for his brief self-introduction.

Patrick Hanley, Ph.D.: Hello, my name is Patrick Hanley. I’m an assistant professor and the director of the cellular therapy laboratory at Children’s National Health System at George Washington University in Washington DC.  I have an interest in cellular therapies, particularly antigen specific t-cells, whether they be virus specific t-cells, or tumor specific t-cells, as well as mesenchymal stromal cells, and I’ve been involved in translating these to probably 15 or more clinical trials over the last 10 years. I’m associated with a number of societies including the Foundation for the Accreditation of Cellular Therapy or FACT. I’m their vice chair on the education committee and I also serve on the accreditation committee. I’m also the co-chair of the  Gene Therapy Committee for the International Society for Cellular Therapy. I’m really committed training the next generation of cellular therapists because, for those of us in the field, who know, it’s quite challenging. Do you find staff at the moment who are trained and competent? So, we have a number of cell therapies that are exciting, but it’s hard to find stuff to make these. With that I’ll turn it over to the next speaker.

James Bauch, Ph.D.: Yes. My name is Dr. Jim Bell. I’m the principal consultant for Bio-analytics Consulting. I’m  a biochemist with46 years’ experience, 35 of which I’ve spent in biotechnology. My experience took me through “Big Pharma”, working for Shering Plough for 28 years, eventually purchased by Merck. My individual molecule experienced includes interferons, monoclonal antibodies, virus vectors as drugs,and also, now more currently, actually bacterial vectors, listeria monocytogenes as inactive drug agents. My specialties are clinical supply release testing, specifications setting, and analytical characterizations. I’m very interested  in talking to the group out there about cellular therapy.

James: We’d like to do introduction slides first. A couple points for myself. Cell therapy and personalized medicines face unique challenges. More so than traditional biologics in the past, and some of the sloppy industry quality, and business practices won’t be acceptable. A lot of this involves data integrity. Making sure that the chain of information from the patient to the production floor, back to the patient or hospital setting. Sometimes is maintained and that’s a real challenge. One of our clients is in phase one. They know the challenges we’ll face if they don’t deal with that problem and they’re already working on it. These products need to be right first time. That’s often not been the case with traditional biologics. Five percent scrap rates have been acceptable, but when that patient is relying on the delivery of that therapy, and it’s individual, they’re not going to be happy. You don’t want five percent of your patients not getting therapies on time.

Manufacturing facilities need to be designed for purpose, and there’s going to be some real challenges here over traditional manufacturing facilities. They’ll need to be flexible, scalable and efficient. The concept of  “what is a batch area clearance?”  needs to change to assist in this close system and should be used wherever possible. Again, good data integration and information of technologies is going to be key, and there are systems with technologies out there that even small companies can benefit from and really need to think strategically about that in terms of how the commercial product will be manufactured very early in development. With that, I’d like to turn it over to Patrick.

Patrick:  I wanted to give you an economic perspective since that’s where I’m coming from. It’s interesting because bone marrow transplant was really one of the first widespread cell therapies that’s been done throughout the world. It’s traditionally been done in centers of excellence. So, every single hospital does not have a bone marrow transplant program and I think that’s where cell therapies are going. I think we’ll find that car t cells are an example of this. So, “Big Pharma” now will only go to these centers of excellence that they have qualified to be suitable for their t-cells. The model of bone marrow transplant is a decentralized model, so, each bone marrow transplant center makes their own products that are released, they have their own quality system, and then they treat their own patients. This resulted in the formation of the Foundation for the Accreditation of Cellular Therapy as well as ABB, to help standardize these qualities and outcomes so that you didn’t have to go to an MD Anderson, or Mayo Clinic to get the best therapies. You know, there wasn’t such discrepancy  in outcomes, and I think that had tremendous results.  You’re seeing that now come to fruition in cell therapy as well. So now, approved in late stage biotech studies are done in a centralized model. So, you use almost exclusively centralized manufacturing.  Then that product is actually purchased back by the hospital to then infuse to the patient. So, in this case, the hospital serves as a supplier to the pharmaceutical company, but it also serves as a customer, which is a really interesting relationship. It’s a very complex process and has a lot of increased costs because of that shipment back and forth and also the qualification and things like that that are needed for that process, and so, the question I always ask is, is there a place for decentralized manufacturing, if we had robust bioreactor for systems that are closed and unreliable? You know, it would it be cheaper to manufacturer at the site rather than shipping products back and forth? Allogeneic cells may obviate the need for a decent trials manufacturing. So, right now, all these car t cell products are autologous, but there are companies that are testing them in early phase studies, that are testing allogeneic cells, and it will be interesting to see how these work, but this requires that we’re able to manufacturers at a much larger scale than we’re currently doing, because you can imagine the testing required for these cells is quite expensive and so you want to have as a little as few batches as possible.

Terri: Thank you panelists for your overviews and talking points. We’ll now open it up for your questions. Simply type your questions into the question box. Our goal today is to answer any and all questions. However, if we do run out of time, those of you in operating companies, we will answer your questions later on today. Now, for our first question: In your experience, what is the biggest challenge for you in translating therapies to the clinic? Patrick, maybe that one’s for you.

Patrick: Sure. So, I think there’s a number of challenges. I think as a director of a manufacturing facility, one of the challenges is trying to keep up with the demand and the pace of the clinical investigators. Oftentimes the second that, that IND is approved by the FDA, there are patients lined up out the door that the physicians want to treat and yet, you know, we’re just now implementing that protocol, finishing the validations, making sure that we have staff trained to make these cells and so, that lag can oftentimes be problematic, and we’ve taken steps to address that by, you know, ensuring that we have these implementation meetings where the physicians have to sign off that they attended these meetings and only now is it okay to enroll patients and things like that, but, you know, all of us want to make sure that we have products made for the patients, and that these patients have access to our novel clinical trials, but we want to do it in a safe way. So, that’s one of the hurdles. I think the other hurdle is just the popularity and the success of the cell therapies themselves. So, we have a limited manufacturing space and I think, I only know of one or two manufacturing facilities academic that do not have a queue of patients waiting to receive cells, and so, you know, there’s been a couple of ways to address this. There’s a few institutions who have built 30, 40,000-foot GMP facilities and these are the academic space costing upwards of $50 million dollars. Other groups choose to try and improve their process to close it, to automate it, but there’s no doubt that probably the single greatest challenge that we’re facing right now is meeting the demand of the cell therapy for the patients themselves.

James: Patrick, I have a follow-up question. What do you think you have learned in the academic setting and under such challenging conditions that could benefit people who do their own commercial manufacturing later?

Patrick: So, I think one of the things that I’ve learned is a lot of the tools are already there. You might be able to speak to this more James, but the biologic space in particular antibodies have gone through some of these growing pains already, and so a lot of these bio reactor systems that we’re using now the way, for example, have already been used to make antibodies and so, you know, just connecting with commercial entities who have this expense experience has helped us meet some of those demands and you know, the more we can automate, the more we can close these systems that the more scalable and the more patients we can accommodate. I don’t know if you, if you can maybe speak to the transition and the antibodies space and the challenges that were overcome there.

James: A lot of it dealt with the expression systems and then sort of standardizing on those and then a purification, after some time became, I would say fairly generic and you know, to develop those processes today, it’s really– Doesn’t take nearly as much effort is as a historically it took, and so, that came from process of understanding. So, I think integrating these technologies to understand how to work with different types of cells in a more generic sense is something that is just going to take time and experience.

Jim: I’d to throw in one particular issue that I’ve found to be a rather overarching problem for what I call highly personalized therapies, and that’s simply the cost effectiveness for any organization undertaking development of a drama that is truly highly personalized to an individual patient, and we’ve struggled with this. I shouldn’t say we. I should say the company that I’ve consulted with, and once or twice has struggled with this issue, and I think that this is more of a business question and a science question, but it’s in the forefront here because to effectively develop a consistent therapy, and make sure that it’s pure and stable and effective, for single or maybe even a small class patients, say orphan drug patients, is a challenge of itself because it drives up the cost of the individual therapy. Think about that.

Patrick: Jim, you’re absolutely right. I went to a prominent venture capitalist in the Boston area that just had the concept for a company that’s now up and running and public, and back then they were aware of that problem, and so even for that company was launched, they were thinking about that, and I can tell you is that that thinking is integrated into that company in terms of the science and engineering and their approach from day one. So, that’s an important point.

Jim: I’m not so sure. I don’t have a good answer for it. However, anyone venturing into the area and even attempting at the very basic clinical trials has to realize the cost effectiveness of what the treatment is.

Patrick: Well, I think the cost of goods is reflected in the cost of these novel therapies. If you take the car t cells, for example, Novartis says Cambria, with his price at $475,000, but if you look at the costs of manufacturing cells, depending on who was quoting it, I believe Carl June is quoted as low as $20,000 a dose. Others have claimed 80,000 to $100,000 a dose, but you’re still looking at a five-x multiplier there. So, you know, but the problem is not the return for their pharmaceutical companies, it’s just that that sticker shock of $500,000. You know, you’re looking at a onetime potentially curative treatment versus a therapy that could cost way more if it was given on a monthly basis, but I like to quote Bruce Levine here, you know, he equates the car t cells to a model t. If you were to buy a model t in the early 1900s, they cost would be prohibitively expensive, but if you were to buy a car, now, you know, almost every person in the US has a car or I’m not sure what the percentage is, but it’s not prohibitively expensive, and I think that’s the hope for cellular therapies as we develop new technologies, as we make better bio reactors, we get a better sense of what testing is required and is not required. I think these costs will come down, and I think the FDA is willing to work, you know, they just work with us. They just released six new guidance’s related to gene therapy, and some of these were dropping a lot of the testing that has been required in the past. So, I think we will see costs coming down. We just need to make sure that the therapies themselves are good enough and efficacious enough that insurance companies will be willing to pay the high cost until those costs drop.

Jim: Exactly. If you have something that cures a particular type of cancer, then you’ll have a better chance of moving this forward, but if it’s for less grievous medical problem, it’s very difficult.

Terri: Yeah, and Patrick, I’m glad you mentioned the new guidance’s for cell therapy because I have a GMP question here. In your experience, or James or Jim as well, are there any recurring GMP deficiencies you’ve noticed at facility’s performing cell therapy manufacturing? Are there any areas that are generally weak? Anybody?

James: I haven’t gone in and studied observations in a serious specific to gene therapies, but you know, if you look at it from a risk standpoint, certainly any area that’s going to receive scrutiny for sure, there’s going to be any kind of a septic operation or transfer at any opportunity for any kind of adventitious agent to get into the process. I mean, the FDA looks at risk from adventitious agents from their early history and it’s almost always invariably one of the first things they look at when they’re inspecting or looking at any process or filing. So, you know, anyone who has any concerns in those areas, you know, those are the first areas in terms of GMP compliance because they relate directly to patient risk, right? So, I think that’s how I’d answer that question. So, it wouldn’t surprise me if that’s where are most of any kind of, you know, inspection observations are made in terms of numbers because that’s the number one area that they’re almost invariably going to focus on and try to poke holes into it. I hope that helps.

Patrick: Yeah, I second that. Oh, go ahead? Go ahead, Jim.

Jim: I was just going to add one more thing. Throw this one out on the table. In addition to the adventitious agents when I’ve seen is that anytime we have a situation where you’re trying to manufacture therapies for multiple patients, but the therapies turn out to be very, very similar to one another. I mean, this is not like the difference between streptomycin and penicillin, right? So, these therapies are very, very, very similar. The problem is chain of control and making sure that as you move through the manufacturing process and the testing process, that these incredibly similar compounds that are now patient specific, that everything is maintained from a high level of GMP standard and there’s no mix ups because everything starts out with very similar technology and very similar identification numbers and so forth. So, this is something that I’ve seen as a touchy point in manufacturing facilities that are engaging in multiple products that are highly, highly similar.

Patrick: Yeah, you’re right. One of the challenges that you bring up is PHI. So, when you collect the apheresis products at a hospital in institution, there’s PHI associated with that, apheresis product. There’s also labeling that’s specific to the institution. So, there’s donation identification number, and then you send off that product to a pharmaceutical company and they’re going to put their own number on it. Some companies do not want identifying information on the product, and so then when you get that product back, you need to make sure that there’s a way to link the product to the patient, and we’ve had this problem before where, the CFA doesn’t match exactly the products because they put a suffix on it that designate it a lot, but we didn’t know that, and they also didn’t have the patient information on it and the clinical research associates are the ones who have the linker, not our manufacturing facility, and so, these are a lot of the challenges. I’m not sure that they’re, I mean they are deficiencies, but they haven’t been noted by FDA yet, but these are real challenges and the only way to work through them is to do mock shipments, to do dry runs and things like that, and these are real examples that are happening and it’s not just our program. I’ve heard horror stories from other programs as well where, but consecutive batches have been manufactured from the same institution and they make up some of the lot numbers.

Jim: Exactly.

James: Yeah. Thanks. That really gets it. Know my introductory comments about the importance of, you know, integrating data systems and data integrity in your quality system into all that. All right, thanks. Thanks. Terri next question.

Terri: Okay, great. I do have another question here. What is the appropriate COGs for cell therapy? Any thoughts on measuring COGs for these therapies?

James: I think this is more for you consultants. You guys make the big bucks. You said CRG? COG?

Jim: COG, cost of goods, right? Cost of goods.

James: I can tell you, you know, having looked at it at some of this in terms of facilities design, it’s again, going back, you’re not going to be able to produce these therapies for just nutritionals, sweet clearance for each sample or each product that you’re producing a large facility. So again, you know, developing the procedures and controls around what’s that controlled space for that sample, maintaining that data integrity. So, that you can have many samples, I’m being processed in the same production suite, is a clear driver towards driving those costs of goods down. So, again, automation is going to be very important in doing that and many of these processes will need to scale up in parallel. They won’t be able to scale based on volume. So again, integrating those kinds of designs into the facility design so that, you know, they’re modular, easily expandable and looking at equipment utilization and its downtime, up times and maintaining those schedules. It’s going to be a lot of operational integration, operational excellence activities and data integration to really drive those costs of goods down.

Patrick: Another huge contributes to the cost of goods is, an in therapy anyway. The viral vectors that are used for transduction per lot, I’d say this is not an exact number, but between 500,000 to a million dollars for each lot of vector that you’re manufacturing. So, not cheap, and I think where we’re going to drive down cost of goods is to use non-viral vector transduction methods which are not developed yet.

James: Interesting.

Terri: Well, I think that answered your question. I  have another question: What is the biggest challenge for you in moving towards commercialization? I think we touched on it, but can one of you elaborate?

James: I’ll launch that when — Another unique challenge to these therapies is, more or less fixing your process as early as you can, and really controlling and minimizing changes after that so that the inevitable regulatory questions, that would resolve are either easily handled or you don’t get. The best regulatory question is not that they get the question to begin with, right. So, because the, you know, the process is– Years ago for traditional biologics, that was the process was the product, then we moved away with that with increased our process understanding and science. Right now, for many of these processes, you know, the product is the process unfortunately, but in a science again, advances, you know, that will shift, but the current state is now is to try to minimize, you know, trying to get as much process understanding early and then try to fix the process as much as possible early in the process development cycle.

Jim: I’ll add one point here. Over the years, I’ve companies that I’ve worked with and for, one of the biggest hang ups has been finding biological essay that is usually expresses– It’s usually a surrogate for the end point application, and why do I say that because what we’re talking about here are therapies that are very hard to reach an end point. Reach an end point of what is successful. So, you fall back on surrogate biological essays that more simplistic and the problem is that they’re hard to maintain in the laboratory, even being more simplistic. They’re still hard to maintain in the laboratory setting, yet that particular essay has to somehow, you have to have a scientific connection to the eventual efficacy of the drug and over the years, it’s been almost the first thing that you have to pin down as you envision a program moving forward. Of course, that particular bio essay, will help you or will be the cornerstone of your purification scheme, and it will also be the cornerstone of your consistency testing batch to batch. So, I will add that as a, you know, biological essay problems.

James: Thank you Jim, because I had that as an afterthought, as that, in terms of fixing that process, if you make any changes, if you could come back and anchor it, did that kind of data that you just mentioned, then you’re at a much, much better position. So, it’s invaluable from that standpoint as well.

Patrick: I think it’s an interesting time to be in the field because cell therapy is, you know, living drug, right? So, it is in some ways harder to pin that biological function, but at the same time FDA seems to be amenable to a simple essay like Interferon Gamma Release as a potent CSA, and that’s what Novartis used for their camera approval, and if you look at the error bars on that interferon gamma, they censored what the scale was, but it seems to be a large, and so, it’s almost as if FDA has appreciated the fact that there is clinical endpoints here and they don’t want the potent CSA to get in the way. Now, you know, I’m not involved enough to know the intricacies of that, but it does seem that the agency will be willing to work with you, you know, if you have good data. Now, I will say, there are a number of mechanisms now to engage the agency early, whether that be the, our mat, a designation and the breakthrough designations and things like that. Which is good. I think that the agency is trying to partner with companies now to find therapies that work for these rare indications and cancer. So, you know, that is a good thing.

James: Patrick, that’s great advice. I’ve seen too many clients I think are too hesitant to reach out to right out through agency is out of, I think some sort of unfounded fears.

Patrick: Yeah. Now I can chime in for some of our challenges, and that scale, and one of the, James has mentioned, you know, closed systems and we’re not there, you know, we have these great therapies, they seem to be efficacious in early phase studies, but we’re making t cells in 24 of our plates. That’s probably not going to cut it. You know, and so we need to find ways to put these in close systems and make them more scalable to make them easier to make sure that they don’t take a month to make. So, these are the real challenges I face, and it’s going to take a lot of time and money and effort to change that, and I think it’ll be worth the effort, but that’s the challenge we have right now, and that’s true for almost every one of our therapies.

Terri: Thank you. I have another question here: What types of controls have you seen manufacturers put in place to prevent product mix ups?

James: Go ahead Patrick.

Patrick: So, we do identity testing as everyone does, but our identity testing is actually per donor. That’s one unique aspect of cell therapy and manufacturing where it is, you can tell whether the product, not visually, but if you do it, genetically, you can tell the difference between the products. So, at the end of our release, we make sure that the product of blood bloody came in is the same HLA type, for example as the product that we’re releasing and there’s no contaminating DNA or HLA molecules in that final product. So, to us that means at least it’s the same donor that work cryopreserving. So, that’s one way that we check it, in terms of preventing it, you know, the best facilities have enough space to dedicate one queen room per product. You know, we don’t have that luxury for phase one in our academic GMP facility, but you know, we have changed over procedures. We only work on one product at a time in that room. You know, we have systems for checks to people have to check the product and verify calculations and all that, you know, GMP that we all know about. So, those are our procedures. I think the biggest check that was that identity check at the end.

Jim: I would also add to that. In addition to identity, I would add that whenever possible, use disposable equipment, filling lines, tanks, whatever, during the manufacturing process and that will prevent cross contamination or at least to some degree.

Patrick: Yeah. I don’t know if any of the systems are actually not disposable in our field. I’m not sure

Jim: As it gets larger, and they get into larger compounding and filling operations, they will be a fork in the road and the decision will have to be made. It’s always more proven to use disposable surfaces whenever possible.

James: I think barcodes and those types of systems of people have used, uh, even in lab environments then integrating those with your data systems as one of the best ways and then in terms of the user interface around those systems. Again, integrating those systems so that operators and people are prompt that with data and information around what’s happening, so that mistakes are prevented from happening in his manufacturing execution systems.

Terri: Thank you. We have another question here: What is the greatest risk from a patient safety point of view?

James: I touched a little bit on this, previously, in many respects, it’s going to be, you know, the, in many cases is going to be a risk of adventitious agents thought that that’s the only risk certainly out there. So, whether that be viral, whether that be bacterial, you know, one of the challenges for some of these therapies is that the quality release testing, is it going to have time to do a traditional sterility test? And so, companies are looking at the faster systems to do rapid IDs. In some cases, there won’t be time to wait even for those results and the therapy will have to go to the patient, but at least they’ll get the results and then have her something that needs to be done prophylactically with antibiotics so that treating physician is aware of those results. Then, you know, that needs to be integrated also into the clinical and treatment protocols in terms of how that is handled.

Patrick: I think that the greatest risk is that the patient gets another patient’s product, and in that reality for most other drugs because they’re labeled differently, they come in different files, in different colors and things like that, but you know, when you’re looking at the product, you know, every single bag looks the exact same. The only differences is, is the patient’s name on the product, and you know, you think that that wouldn’t happen because of the name, but to me that’s, that’s the worst thing that could happen is that, that would cause even worse a cytokine release syndrome and things like that. So, to me that’s the biggest risk.

Jim: I agree.

James: Yeah.

Terri: Okay. I have another question here, and this could probably take the rest of the time, but we’ll try to answer this question. Where do you see manufacturing in five years or so?

James: I guess I should take the first stab of that, that I’ve been on a couple of times, you know, already in the call. It’s really integration of those data systems automation and enclosed systems and one of the things I, I’ve seen different that gives me a lot of optimism around this was that, you know, I was recently at the ISE conference in Canada in Toronto and I was actually shocked at the vendor representation at that conference. At this stage in the development of these therapies, you never, you didn’t see that with, with antibodies, and so, there’s a lot of innovation now I think companies are recognizing there’s a lot of opportunity here. So, I think the suppliers and vendors to the industry are going to be very innovative, and so, I think paying attention to what’s going out there and working with those suppliers and vendors and helping them advance their technologies and adapt their technologies here needs will drive the manufacturing systems so that these things are more automated, faster through puts, you know, less risk, lower costs of goods and you name it. So, I think the innovation cycles in some respects, a relatively speaking, will be much faster for these therapies than they were for antibodies.

Patrick: You know, we’ve talked about closed systems. I think that’s where we’re going to be. In the last month, I’ve already seen two new buy records system systems come out, one of them is actually been released, but I’m one from Torque, they’re the ones who make the Aisle 15 backpacks, I don’t think they like to call it backpack anymore, but they’ve come out with the slipstream, which I’m their VP of manufacturing calls a bread maker, and it’s basically an all in one system for making their t cells, antigen specific t cells, and another company I think is coming out with another type of bioreactor, so there’s clearly identified need from industry for these bioreactors, and I think in a few years, I’m going to turn this to 10 years as well, I think it going to go the route of bone marrow transplant. Bone marrow transplant, we went from giving, you know, entire bone marrow products to now, we’re selecting which parts of draft we want to give, and which parts we want to save, and which parts we wanted to plead, and give later, and things like that.

So, you know, I think in 10 years will be easily able to select cell populations and expand just those cell populations and expand just those cell populations and give them back. So, you can, you know, Juno has done some of this, so they’ve selected CD4 and CD8 and grown them independently and combine them later, so that they can dictate the ratio of their CD4 and CD8 to the car t cell final product, but it’s very costly. You’re talking about $25,000 for each cell selection, but I think that’s going to be easy. I think it’s going to be an all in one bioreactor in 10 years, and so you can make kind of, you know, design your own products kind of thing. So, I think, you know, we’re now seeing the cool things that we can do in cell and gene therapy and I think it’s just the start. I think we’re going to find out what works, then be able to fine tune those products.

Terri: Okay. I have another question here: Has a patient product mix up ever occurred that you’re aware of?

Patrick: You mean reaching the patient? I mean, I’ve known that– I know that a company has sent a mixed-up product before, but the quality group caught it and it was not at our facility. You know, it’s possible that it’s happened and, you know, there was no adverse events.  I’m not aware of it in my direct experience. It has probably happened though.

Jim: Why should this particular type of medication be any different than and others? I mean Nick has car. It’s inevitable, but how can we minimize them? I think that should really be the big question and what are the danger points in this particular field? Is it that the naming and the numeration on the particular drug is too similar patient the patient? If so, we have to figure out how to change that.

Patrick: Yep. Yeah. I wouldn’t be surprised if, you know, over the years that the new products that come from Novartis and kite and they come barcoded so that you can scan them. I’m not sure that there are coded right now.

Jim: Well, it also presumes that you put on the right barcode when you did the labeling. So, barcoding is better, but it’s not the end all, right?

James: Yeah, so that’s the big risk.

Patrick: Yeah, I agree is that the label matches the patient, but the cells in the bag don’t match the label.

Jim: Right, right.

Terri: I I have a follow-up question to that: So then, how does dosage form configuration impact patient care?

James: I’ll take the first stab of that, then I’ll use one recent project perhaps as a launching point, but there’s going to be various therapies, but depending on the therapy, a surprisingly amount of thought needs to be put into, especially the clinic setting, the product configurations and the impact of those configurations and how they’re going to be used in the clinical setting has to be thought about, because it ultimately comes down to ensuring that the proper dose is getting to the patient. So, you’re looking in some cases compatibility of materials, you’re looking at, you know, different types of syringes and hold up volumes and those things and then understanding what surgeons and treating physicians sometimes in the clinic, what’s available then and what they’re likely to use. So, part of it is thinking through that and understanding how you want your product to be used, and how and how to make that work in the clinical setting, and a lot of these therapies needs to be thought out and risk assessments performed.

Patrick: I’m not sure I really understood the question. Can one of the panelists, would paraphrase it for her?

Terri: Well, the question was just, how does dosage form configurations impact patient care?

Patrick: That’s what I mean. What do they mean by dosage form configuration?

James: I interpreted the question is the types of containers and dosages and things like that and how that’s presented, you know, to the, you know, caregivers and physicians and so forth.

Patrick: I see. Yeah. So, I guess one of the ways that impacts is, it dictates who can receive the product. You know, this, a lot of the products now are delivered crowd preserved, so you have to have the ability to store the crop preserved product, and then you also have the ability to thaw the crowd preserved product and a lot of the companies insist that it be infused within 30 minutes of buying. So, you know, their limitations there and automatically that limits it to these centers of excellence that I mentioned before.

Jim: Also mixing in whole time for the reconstituted product. I mean, their touchy points and there are things that you have to be aware of and have a handle on before you put it out there in the clinic.

James: Sure.

Terri: Excellent. Well, Dr. Blackwell, it looks like we’ve answered all the questions that have come in.  Dr. Blackwell, do you have any concluding thoughts and we can wrap this up to respect everyone’s time?

James: No, but I appreciate that Terri.  I guess I would start by asking our panelists, thanking them for their time and contributions. This has been very enjoyable. Just to ask them first if they had any concluding thoughts, then I’ll close out.

Patrick: Just I think that this is a really exciting time for us, but it’s still early days, and so I really look forward to seeing what the future has in store, but I think it’s really critical that we make sure that we are, we are around to see the future days and so, you know, we need to make sure that these car t cells are successful because there’s been a lot of investment in cell and gene therapy, and if we can’t see the back end of that, if we’re costing them, the price is too high, or it’s infeasible, then the first couple of programs that have been approved, if they’re not successful, it’s going to really bring down the whole ship. So, we need to make sure we figured that out.

James: Thanks. Jim?

Jim: I’ll add to that that the indications need to be chosen carefully, and I think you’ve already said that, but I’ll phrase it again. The whole field doesn’t move forward if you don’t have good surrogate essays to help you with purification and consistency, and it also doesn’t move forward, if you don’t choose the proper indications to evaluate the drug and the technology.

James: Alright. Thanks so much. Thanks everyone for attending. We hope you came away with some useful insights and a greater understanding of the challenges faced by this field. If anyone has any specific consulting needs on this or any other CMC quality regulatory supply chain or operational excellence topic, please reach out using our contact information on this slide. We love to hear from you. We look forward to sharing our expertise with you in the future. Thank you.

Terri: Thank you everyone. Bye. We’re concluding the webinar now.

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