Transcription: Cell Therapy Expert Panel Discussion

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

Terri Melvin: Welcome everyone to today’s webinar Cell Therapy Expert Panel Discussion. I’m Terri Melvin and I will be today’s moderator. We have with us today four 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. I will now turn it over to our first panelist Dr. James Blackwell.

James Blackwell, PH.D., M.B.A.: Thanks Terri and thanks to everyone in our audience for joining us. I’m James Blackwell. President of The Windshire Group and our hope today is to make new industry friends and acquaintances and help organizations through some of their most pressing questions around this very important and timely topic. Just a couple of house rules before we get started. Please don’t ask anything that contains confidential information. We don’t want it. We don’t mark it in it. And for today’s webinar, we’re not offering any specific advice for anyone’s particular situation and we’re not responsible in any way for any use of our advice or opinions we express. After self-introductions, we will share a few of our personal thoughts about the topic and then we will get started with 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’s development and product companies. I’ve been an industry consultant for more than 12 years assisting with CMC technical aspects for products in all major therapeutic classes and at all stages of the product life cycle. More recently, due to the growth in this area we are doing significantly more work in cell therapy and personalized medicines. All of our panelists have significant experience working in these areas and work with The Windshire Group. I would like to now introduce Jason Carstens for his self-introduction.

Jason Carstens, Ph.D: Thank you James for inviting me to join the panel today. This is Jason Carstens. I have a background in chemical engineering and I’m currently a consultant with Cyatholon Bioscience out of Seattle Washington. I’ve worked in the industry now for over 20 years. First starting out in biological process development and manufacturing in a CMO and then transitioning over to the area of stem cells and T-cells for the last eight years.

Ronald Bordens, Ph.D.: My name is Ronald Bordens. I’ve worked for 35 years in biotechnology area. Currently a consultant for various companies including The Windshire Group. My background is focused in five key areas over my career. Analytical production of pharmaceuticals, management of vectors and delivery systems, selecting and identifying dosage forms as well as the quality control and release of some of these unique dosage forms. Thank you.

Deborah Miller, M.S.: This is Deborah Miller and thank you also for inviting me to the panel. I have over 30 years of experience in pharma, biotech, medical device, and a little bit of forensic testing. I’ve had roles both as directing operations and quality assurance. I kind of straddle both sides of that. For the last 12 years, I’ve been a full-time consultant and I’m currently a senior consultant with The Windshire Group. Let’s turn it back to Terri.

Terri: Thank you. Now we’ll go to our first points to consider slide with Dr. Blackwell.

James: A few of the key points I’d like to make today is that for cell therapy and personalized medicines. It will not be business as usual. Sloppy industry quality and business practices of the past won’t be acceptable. Products need to be right first time and on time. So, in order to accommodate this manufacturing facilities should be designed for purpose which means they should be flexible, scalable, efficient, use closed processing systems wherever possible, and you really need to look for integrating your data and information technologies to assure that we have chain of custody and appliance to our quality standards throughout the supply chain from patient to patient. So, location and size need to account for supply chain and patient delivery. This is often where you need to have conversations with your commercial team as well to understand the demand. A number of patients that are going to be serviced. So, depending on your business model and patient needs that can significantly impact the size and location of these facilities. I think the definition of batch processing and batch area clearance will need to change for economic reasons and I think the regulatory authorities recognize this. You won’t be able to do a single patient in a suite and then do a batch era clearance or bring the next patient sample in. For most of these therapies the economics simply won’t allow that. I think for a good model it’s Biogen’s Luterbach facility even though that’s very large scale in monoclonal antibody. I’ve seen three presentations on that project and in terms of how they’ve integrated data and they’re taking a view towards reducing costs as much as possible that is a model for how this industry will have to approach their production and patient needs. So, system and technologies exist to help even smaller companies start down this road. I encourage companies to start with paper records, make those paper records as simple as possible but with the end in mind in that at some point they will need to transition those to electronic batch records. But being able to integrate all these systems so that you release a batch based on the fact that you know what your deviations are early, and release based on exception. This will allow timely patient delivery. Thanks Terri.

Terri: Okay. Great. Now we’re going to go to Dr. Castens.

Jason: Thanks. So, the main purpose of this slide is really to remind people about the fundamental approach of building a quality focused manufacturing strategy and really thinking about the end goals. We’ve learned a lot over the last 30 years in the manufacture of proteins and more traditional biologics and one of these same concepts can be applied to the cell therapy industry much like what James was just saying. I think we need to not be sloppy and be very purposeful and how we approach manufacturing strategies. One of the places that first starts with is the Quality Target Product Profile (QTPP). Which is a very important tool so that the proctor team can come to consensus on what exactly is they’re trying to achieve with the product. I’ve seen all too often that a team will talk about these topics and think they have consensus and understanding but there’s nothing like really precisely documenting the facts and hypotheses and assumptions to really drive discussion and come to consensus. This is intended to be a living document. This should be revised on a regular basis as information is developed and as plans are progressed. From a manufacturing perspective, this really sets a critical foundation for identifying that the critical quality attributes of the product and both the short term and long-term manufacturing requirements. And in particular for cell therapy products, try and identify the mechanism of action so the product can be appropriately characterized, and potency and safety assays developed. I also consider cell therapy manufacturing really interesting and I consider it a manufacturing continuum that starts in the clinic with the sourcing of the starting tissue which are then of course transported to some GMP manufacturing facility where it’s processed and then brought back to the clinic for administration. Steps that occur outside of the walls of the manufacturing facility can be critical to process performance and product quality. The QTPP is where one can start to document that and understand what those steps are especially when it involves the clinical setting and that data interface with the clinical team. That can then lead to the control strategy which is also a living document that will grow and change with time and, really, when ideally should start that very early. Again, I’ve seen many times where at a company they get too busy and don’t take the time to document these elements and really put together a plan. And by documenting your process concern is an excellent communication tool to make sure the team has visibility into the process. So, each functional area has input to do their job effectively and really understand what the critical process parameters are and prioritize where resources should be best spent. So, in somewhere I think this is a very valuable tool to really do your strategic planning and keep some of the critical parameters in mind, so you can look think toward the end which is your main goal of a regulatory submission.

Terri: Thank you Dr. Carstens. Now we’ll go to Dr. Bordens.

Ronald: I just heard several important topics that have come up over many years, but I think more so in the last few years in dealing with these personalized strategies for delivering either a drug or a set of antigens. And a lot of times in the characterization and bio-potency testing, we see a lot of difficulty of companies trying to figure out what’s characterization, what’s potency, sometimes potency is mixed up with the infectivity of the vector and that leads to the GMP production of cells and the delivery vectors which most of my experience has been in delivery vectors either microbial or viral. A little less on the delivery using transformed cells or hybridized cells. But the concept is the same and the producing the cell line, storing it properly, having enough of the material for multiple doses, all of those things really lead to a great deal of effort within the companies. And from some of my experience, I think that the younger companies have not really thought about it carefully enough and haven’t been able to bring to the table the necessary experience for doing that. Their experience sometimes is more weighted to the research side or the development side but less to the practical side of what do you do with this once you have identified your target drug? So, in managing the personalized cells and vector supplies that really becomes sort of in the eyes the beholder or what is going to be the storage conditions? Are those storage conditions going to be suitable for shipping? Developing those conditions with the appropriate stability studies. Consent sometimes be a very challenging thing. For example, in microbial if your bug doesn’t grow long enough, your stability in free stores can be reduced. And in the effort to try to finish things as quickly as possible, a lot of times the correct studies aren’t done by the people involved in trying to establish the storage conditions. And then that leads to the dosage form and how the patient gets the drug. More recently, some of the things that I’ve been looking at is delivering by IV bag. How much does the patient get in the infusion process? How is it delivered? For example, a nurse might inject the drug into an IV bag in a hospital setting but what are they usually putting in there. They’re putting in an antibiotic or something that’s relatively state safe. But if you’re putting something in like an attenuated bacteria what kind of safety precautions do you have to take during that injection process to protect the nurse and the staffs that are going to be delivering those drugs? Or do you have that part done in the pharmacy? So, some decisions about how the drug is delivered is impacted by the dosage form and what your requirements are going to be to get this drug to the patient? Producing the drug at stability is important – batch size, your quality systems. When you look at batch size, sometimes these things were made you know once and the patient may get you know three or four courses. They don’t have to have a large batch size or the ability to make it again. In terms of making the batch, how is the active part of the drug going to be characterized? What’s the potency of it? Is it an antigen presentation drug? Is it a direct peptide dosing? Each one of those presents a different set of difficulties in establishing the batch size stability and the quality systems to monitor all that.

Terri: Thank you. And now we’ll go to Deborah Miller.

Deborah: As you addressed the challenges that the panelist has set before you, you may have picked up that the requirement for documentation is going to expand very rapidly if you haven’t already experienced that. You want to consider controlling the information and communication now for efficiency. But as you grow, if you establish your system simply and have a good framework, you can work towards compliance and keeping in line with Dr. Blackwell’s right time, first time. If you set it up right now and you standardize it, you will be able to follow that road to keeping it simple. Some of the things to consider, with all of the electronic means available to us including email. How do we standardize our file naming protocol so that everyone understands it the same way? And how do we control those files as we route drafts around and have reviews and control which is the most current record with the most current reviews? Most of us now are depending on some sort of an email process or a messaging process to communicate vital information. Yet sometimes we don’t think about the subject line or jumping on one email with another subject halfway through which is really a resource waste for people trying to sort out what information is important and what they need to react to. If we put these processes and control early and not have a lot of rules but just kind of guide people to standardize their communication, it’ll be a lot easier to wade through it and to convert it as you work towards your compliance documents. And let’s not forget about documenting training. Early on, we typically don’t think of documenting training. But again, if you can set up just simple processes where people have read and understood or had a familiarization session on key critical training, you can use that as a platform to move on and work towards your training records in the training system when you’re ready to develop that. So, all of these documentation issues work towards your ‘right time, first time’ and saving your resources by not going back and rehashing all of your communications and trying to find things that you can’t find. Back to Terri.

Terri: Thank you to all the panelists for your overview. Let’s get to the exciting part now. We are open for questions. So, 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 and we don’t answer your question live for those that developing and product companies we will answer your questions after the webinar concludes Okay, let’s see if we have any questions. I do have one question to start us off. How does dosage form configurations impact patient care? I think Dr. Bordens touched upon that earlier. Ron, do you want to take that one?

Ronald: Yeah. I think that I touched on it in the introduction. There’s a number of different pitfalls that we stepped into along the way. Sometimes we try to be too sophisticated. So, for example, instead of putting our dosage form in a vial, let’s say 10 ml vial, producing it and making it a simple formulation, we’re very quick to try to build some sort of patient friendly injection device or something that might be a very, very complex to bring to market with a lot of moving parts. And that’s kind of nice for the patient population. So, we take a simple example like insulin. A delivery pen for insulin makes a lot of sense but it’s for a mature product that went through a lot of iterations of standard dosage form delivery. My preference is start off simple with straightforward dosage form. You can get it into your clinical studies. You can move it along. You can even take it right through phase three and ultimately get an approval with it and then post approvals start to think about what kind of more sophisticated or more patient friendly delivery systems you might want to use. We see examples of that. If you think about delivery of some of the monoclonals, they have a pen device for Enbrel but at certain point in the reimbursement schedule, to get reimbursed for it, the patient has to switch to an IV infusion, so they get paid through a Medicare system. So, not only do you have to have them dosage form for your project, but you have to think ahead of what your patient population is going to be and how you sort of evolve in that dosage form and come up with something that’s going to optimize the market for the greatest return.

Jason: Well, I was going to jump in to say that when it comes to cell therapies, one of the biggest questions that a company will generally come across the beginning is whether or not they want to deliver a fresh product or frozen products. Dendreon was one of the first companies that entered the cell therapy area and they went with a fresh product which has as its advantages and you don’t have to worry about how to preserve the cells but it also creates a number of disadvantages in terms of the logistics of manufacturing and time of delivery to the patients as well as to really assure yourself you can deliver and ship the product appropriately to make sure it arrives in a viable state. The other risks with fresh cells is you don’t necessarily have all the time you’d like to do all your safety and release testing. Whereas with frozen cells I think in general the consensus is that the industry is trying to move in that direction because it presents a number of advantages in terms of manufacturability and the timing, being able to complete your testing, but it does create other challenges associated with the recovery of the cells as well as something that really needs to be thought through like how is the product delivered to the clinical site stored at the clinical site it and administered in terms of power the cells. Is it at bedside?] is it done in a laboratory? And so, a range of things to consider at least with respect to fresh versus frozen.

James: This is James. You bring up a good example Jason. Dendreon, their cost of goods was so high that they went out of business. So, that’s an important aspect. And Ron pointed out making a later change in the process. Much more settled for these therapies than traditional biologics is that the effort and characterization work that needs to be done as much earlier in the process so that you reduce the need for making changes later. And if you do make changes, you have a better understanding of the impact of those changes.

Ronald: Yeah. Absolutely.

Terri: Okay. Great. Thank you! I think that answered your question. If it didn’t, please let me know. I have another question here. What are typical CQA’s for cell therapy? Which CQA’s are difficult to measure and which are difficult to control?

James: That’s a lot of questions. Ron, do you want to take that one or start that out?

Ronald: Yeah. I haven’t worked with the actual cell therapies, but I know in this selection of a portfolio of quality attribute testings, we find that in the development process a great deal of scatter. So, you know for example, for a bacterial vector, you have a number of different possibilities for an infectivity assay. Do you use fax? Do you use a plate method? Do you use a cell-based method to look for infectivity in a cell with a surrogate marker? All of those things are important. And then you’ll get to a certain point where you have three or four tests and you’ve collected data on different subsets of different tests and how do you select the one that you want. I think that makes the whole quality attribute testing whether it’s characterization or the quality release of the test difficult because you don’t have one synonymous database for all of the different tests. You have some from column A, some from column B, and then you decide based on a limited data set and you go into validation. So, the final selection becomes very very difficult to decide which test you’re going to put in because you really don’t have a great deal of data saying one is better than the other. I might add to that the difference between infectivity or the presentation cell. So, in your case of your cell therapies, let’s say you’re making a sensitized T cell. In that sensitized T cell is going to affect some downstream cell activation. How do you measure that downstream cell activation for potency? Because I’ve run into a lot of difficulty with that lately and picking a quality test for a presentation antigen that’s being presented by a t-cell and I haven’t come up with a great deal of good solutions for it.

James: This is James. I would think that understanding the mechanism of action is extremely important. Understanding how the therapy works within the patient and then working backwards from that to the cell attributes and characterization. We’re dealing with living organisms. So, those you know can be phenotypic, genotypic, physical, microbiological. Understanding and trying to reduce that down to the critical quality attributes is the challenge. But the more you understand that, the better you be able to control your process and you’ll be in a much better position to deliver effective drug candidates to the patient.

Jason: This is Jason. I would concur, and I think I would put potency at the top of my list, understanding the mechanisms of action. It’s related to that also, its maybe the identity as well. In the case of cell therapy products of t-cells for example, when we’re delivering these products, we may have a mix of cd8 cells, cd4 cells, memory cell, effector cells, a plethora of different phenotypes and subtypes that are in there and so really trying to understand what the actual active cell is? We can have bystander cells that we think are bystanders but are perhaps actually serving some sort of function. And then also related to the potency, maybe there’s a still a lack of understanding of exactly what potency means. Again, using t-cells as an example, it could be direct killing. It could be the way that cells would interact with other cells. It could be their growth and expansion potential, could be the cytokines they release. And so, really trying to hone in on methods of action and potency in my mind is one of the keys CQA’s that we definitely want to spend some time early on.

Ronald: And it seems like the argument that like you make your submissions to the different regulatory authorities and one of the top questions that they always come back to us with is what’s your potency assay? Right. We might have a lot of things that test the quality attribute and say, well, we have what we say we have. But they seem to want some sort of functional assay that reflects what you are doing and what you’re delivering to the patient that so to say that your drug is efficacious in the way that you want. And it doesn’t appear that you can take it and link it to a clinical outcome. You need something that’s laboratory based. That’s hard to do.

Terri: If you have a follow-up question, please type it in the question box. We do have another question. What are some of the biggest mistakes small companies commonly make in process development in your experience.

Jason: I think I’m happy to start out with that one as well. I think number one is the lack of planning that kind of goes back to the slide that I showed just really again kind of thinking with the end in mind and really putting together a good strategic plan. Specifically, one of the things I always tell people when I’ve been working with industry is that I transferred just dozens and dozens of processes between different sites and manufacturing facilities to scale-up. And universally with every process transfer, I always say you can expect problems in the raw materials and the analytical methods. With regards to the raw materials, I think it’s just something that’s kind of taken for granted. It may be not given all the attention that it should be. But I’ve seen numerous mistakes, small mistakes, that can pop up and be very important mistakes. Just using a different version of a raw material, having a recipe that’s not quite the same, and you have a different order of addition, maybe doesn’t quite scaled the same way. So, really paying attention to the raw materials and making sure that they’re really under control. Development, manufacturing using the same version of materials. And then in the analytics, it’s just so key in being able to really characterize your product and really convince yourself that as you make process changes and develop a process that you’re developing, you know the right product and you could monitor process changes. And so, really spend time to make sure you understand your analytics that it’s qualified appropriately or validated appropriately.

Deborah: I would add on to that. You have to develop your own user requirement specifications for your equipment and your raw materials. You cannot rely on your vendors or your suppliers to tell you what you need. You have to figure that out for yourself and define it before you go out and start purchasing things. For instance, there are different types of refrigerators and freezers depending on the range that you need to control. Some of them are managed with a control dial that is not very specific and some of them the kind of a freezer that you want for your stability studies, for instance, will have very important controls and integrated with the condenser to make sure that you can qualify it and control it within the tight range that you need. But your supplier is not going to know what you need. You have to define your specifications in advance before you start putting money down for resources.

James: I guess mine is a non-technical answer. It’s trying to do too much with too little. And there’s I would say the only anecdote to that is you know bringing help, targeted help, the right help at the right time can really save you ultimately a lot of time and money in the long run.

Terri: I have another question. We are thinking about building our own manufacturing facility. Where do we start? What kind of things should we be thinking about?

James: I’ll start with that one. It’s what I said at the beginning, starting with the end in mind. Understanding what ultimately how this is going to be commercialized? So, to extent you bring that thinking forward and start to thinking about it now and incorporating that into your processes as you develop. That’ll help standardize what you’re doing and reduce any kind of tech transfer or technical issues that may come up later. I use the example of moving to electronic batch records sooner as opposed to later. The technologies have advanced now so that this isn’t nearly as onerous as it used to be in the past. I also think that starting the conceptual design process early is very beneficial and in doing that also thinking about the integration of these information technologies which can actually influence the design of the facility and that helps with your business model planning as well. So, understanding the cost and economics of those feeds back into the commercial thinking for the company as well.

Jason: I can jump in as well next. I think this was a great question and a great topic. We could actually spend like four hours on a webinar talking about this particular topic. For me, being an Excel junkie, one of the places that I always like to start is really building some sort of mathematical Excel model that describes your manufacturing process. So, you can really define your raw material requirement to yield, your processing times, your equipment requirements. Once, you have this model in place then you can start to look at and how it scales in terms of scale up or especially in a case of cell therapy scaling out. And then this will be key to really kind of starting that conceptual design your manufacturing facility and just at a really high-level sketching out how much square footage do you need, what are the resource requirements, laboratory requirements, clean rooms, space requirements, and this is then where you can have the information that you can then take to architects or contractors or real estate professionals that have experience in biotech manufacturing. So, you can at least make a high-level estimate of what type of capital investment and operating expenses you’re looking at. And that’s where you can then go back and really go back to the fundamental question of do you want to build your own manufacturing facility or not? I find the cell therapy because it’s such a new nascent field, the technology is really just changing so rapidly as suppliers, vendors come out with new processing technologies and work with the customers that I found it can be kind of challenging sometimes to actually put together your conceptual design because your process may be changing so fast. But I would agree with James. I think you really do need to start with that conceptual design so that you can start getting the economics worked out and make some decisions about whether or not you want to build or outsource. And of course, it also depends on the company and your product lifecycle and whether or not you really think you need to build a manufacturing facility to have the capacity or if you’re actually better served to go to a CMO and use their existing infrastructure and use that capital investment for something else such as reinvesting in your development or maybe other products or building your company until you can commit yourself that you really are at a position where you can support a manufacturing facility. It’s a large capital investment as well as a large operational expense as well that really needs to be thought through. So, again, this really a can be a very in-depth topic that one could spend time thinking through.

Deborah: I would also add to that, that you have to look at the community that you’re building to see what your people resources are? If there are university resources, if there’s a good mix of trained people or if you’re going to bring in college graduates and train them yourself, if you’re in location that people wanted to move to or if you have the right staff availability.

Jason: That’s actually a really good point. In fact, that reminds me of another point I wanted to add, which is, you actually have to look and see if there actually are facilities available. It kind of depends upon where in the country or the world you’re located, speaking for myself here in Seattle, it can be very difficult to find facilities that are suitable for building a manufacturing facility that already exists. If you want to spend even more on building our own facility, you can. But trying to lease or find an existing suitable biotech space can be very challenging in Seattle and on most of the west coast as well. I’m not quite sure the situation on the East Coast but I would imagine that certain areas such as around Boston are very similar. And so, just trying to identify a space could be very challenging to do that.

Terri: Thank you. We have follow-up question about what you just said Jason. So, if you do find a GMP manufacturer, should you just expect them to meet the pertinent requirements? And if you do, I would assume you would have to do an on-site audit, what would you look for if you were doing an on-site audit of a protein manufacturer?

James: I guess I’ll start without it. I would never expect anyone to deliver I want without me being intimately involved with and partnering with that organization. And it goes way beyond an audit. Obviously, before you make any decision, you should do an audit for making a final decision of going with any CMO.

Jason: Yeah. I would agree with James. It’s a long process that one has to go through working with the CMO. You certainly want to put together your RFP. And again, this kind of goes back to really having great documentation for what your process is. What your starting materials are. Where your critical parameters are. So that you can give this information to the CMO. So, they can do a very thorough assessment of your process and the facility fit. Because without saying I think that I mean it doesn’t go without saying, but you know every facility is different and so they may have these changes and tweaks and modifications to your process in order to make it fit into the CMO facility and fit into their work structure and workflow. So, these are discussions you really have to spend a lot of time going through and really considering and looking at all the different options that are out there so it’s not a simple process, but you definitely want to start with an audit and a thorough technical evaluation of the sketch.

Deborah: James touched on the fact that it’s a partnership and that’s exactly what you want. And following up that, you have to understand what your requirements are going to be compared to the other clients the CMO might have, because if you’re not a high-volume, you need to make sure that they’re going to give you the time that you need for the work that they’re going to do for you.

James: Jason touched on the maker by decision. And I think the decision outsource, you need to know the question you have to always ask is, are they going to be able to make a better-quality product then we can? There’s a saying that if you want something right, do it yourself. But the challenge of doing it right yourself is large and some organizations really underestimate the human resource aspect of this as well and the systems that they need to make it right. One model is use a CMO for development and commercialization with the idea that you’ll make your own manufacturing capacity later with advancing technologies in terms of closed systems and single-use systems. It’s made it easier for organizations to also bring the manufacturing in-house.

Jason: Yeah. I would agree with James. I think that’s actually one of the interesting things about cell therapy manufacturing as compared to proteins. In cell therapy, the capital investment for the equipment and the facilities is usually a little bit or maybe a lot less in some cases compared to a protein manufacturer. You don’t need these large stainless-steel bio reactors or the disposable fire records, chromatography columns and skins, so the scale of manufacturing can be smaller. Although you may have to do more processing lines in parallel. So, capital investment can be smaller. But again back to what James said, I agree that there’s also the human resource element as well in terms of finding skilled staff and then building up the quality systems is a large commitment in terms of just growing your QC staff, your QA organization, building the systems, equipment validation, facility validation, these are things that are not trivial and consume a lot of time to put in place. These are things that by going to a CMO, they’ve already ideally put these systems in place and say now you can just kind of leverage the existing infrastructure they have. So, again, you really have to kind of just think through the pros and cons of each strategy. I think you can go either way. I’ve seen companies here in Seattle using Seattle Genetics as an example. They’re a large successful company that has a commercial product. They’ve relied exclusively on CMO’s at this point in time. And I’ve also seen cases where we have very small companies that decide to build their own manufacturing facility, do their own processing and that solution works fine as well as they want to pursue that. But you just have to kind of understand what you’re getting into.

Ronald: If you’re a small company, I really don’t see a way without partnering with some aspect of what you’re doing. For example, if you’re doing patient specific antigens and you have to have sequencing done on tumor tissues and things like that, you need some sort of company that’s going to do that for you to build your own sequencing facility and having access to a database that’s going to do the comparisons to the normal tissue. It would be extremely expensive. So, I come from few projects that have been exclusively outsourced, more virtual than anything else. And you still run into the same problems. You’re going to run in-house except you save all the costs of building these facilities. So, I’m not in favor of spending the money on building it in-house. I’m more in favor of taking advantage and leveraging somebody else’s expenditures on it. Maybe because of your small company, your funding can be important and if you’re going to shoot a lot of cash on building out GMP suites and qualifying and getting inspected, it might be worth the aggravation bringing a CMO along even if you need two CMOs. One for the development of the process and one for the GMP manufacturing of the goods. I just think it’s easier.

Deborah: And a key document when you’re using a CMO is that quality agreement. There has to be detail and define and understand who is responsible for releasing the product and what builds up to that release of the product.

Ronald: Yeah. That’s really a good point. And its also what information do you kind of take home with you that you have possession of. You know I’ve seen some situations where I’m not happy in that a company gives you a C of A but they don’t give you the actual details of a sequence. I don’t like that. If I’m doing a DNA sequence, I want to see it. You know I don’t want them to assure me that it’s 100% homology with my predicted starting sequence. I really want that data so that it’s got to be upfront in your quality agreement that you’re going to get all this information or it’s where you can get it very fast if you need it.

James: Ron has touched on a couple things. We have a client right now who’s using a third party that does testing of the cell sample. They’re really the early stage and really struggling with the process that the sample is taken, it gets analyzed by third party, they generate data, that data is used to then form an instruction set for the manufacturing floor, that drives a personalized medicine, that personalized medicine then goes back and gets delivered to that patient. Imagine all that information that’s flying around there. They’re really struggling with that.

Ronald: Yes, and what’s the GMP impact on that. I don’t see like these sequencing companies some of them do have like CLIA certification. For that clinical side, you’re taking patient tumor, you’re sequencing it, that’s sort of a clinical test. So, it can’t just be the sequencing lab down the street. They have to have some qualification and certification to be able to do that for the patient specific DNA sequences that you need to make a plasmid or whatever you’re incorporating into your cell line or vector.

Deborah: That’s a good point. So, back to the user requirements, you have to have user requirements for your supplies and services and other vendors besides the CMO.

Jason: I guess one other point I would like to add is the control I think kind of maybe going down the same path of maybe saying they really consider a CMO as there may be a first solution to look at. But one of the flaws that sometimes see when you enter the CMO relationship, you can pass the information off to a CMO and let them run with it and if in reality the sponsor needs to be really actively involved in the work that takes place at the CMO in terms of having little regular project team meetings and maybe a person implant activities and you just can’t turn it over to CMO and let them just go with it. And you’ve not really taking a very active role in the work that’s being done much like the example that Ron gave. I think you also have to be sometimes insistent upon getting information back out of them as well. Having worked as a CMO myself for a number of years, I know that it’s a tough business and you have a lot of customers you’re trying to make happy and a lot of information. So, as a sponsor, you really need to be kind of that squeaky wheel to make sure that you get the information out that you’re looking for and that you really need in order to make sure you can move ahead effectively.

Deborah: Well, I would put in a plug that when you look to staff your quality assurance department, make sure that they understand that relationship with the CMO and are willing to, let’s say, bird-dog it.

Jason: And maybe get an element to it. You really have to view it as a partnership. And to really work through this with the CMO, everybody’s going to make mistakes. Both as the sponsor you’re going to make mistakes or the CMO is going to make mistakes. But really form that partnership in that trust and build a strong relationship up and work through issues as they arise, just be open and honest in the communication. That would be one of the most important things when working with a CMO.

Terri: I think we answered all the questions in the timely manner. So, we’re going to wrap it up here unless anyone else has anything to add. Nope. Okay. Well, thank you for all the great questions today. Thank you to panelists so much for your expert replies and the interaction. If you didn’t get your questions answered live or if you think of one later just let us know. And now I’m going to turn it over to Dr. Blackwell for some closing remarks.

James: Thanks Terri and thanks for everyone for joining us today. If anyone has any specific consulting needs on this or another topic, please know that we’re here to help and reach out to us at any time we’d love to hear from you. The Windshire Group looks forward to sharing our expertise with you in the future. Bye everyone!

Terri: Thank you everyone! Goodbye. Have a great day.

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