Navigating Cell & Gene Therapy: Accelerating Development and Innovation

Welcome back to the Grind, where Joe and Mike continue their exploration of Cell & Gene Therapy with expert Ray Kaczmarek.

In this episode, part 2 of our 4-part series, Ray provides perspective on navigating the development process, highlighting some key factors for success – robust science, integrous data and stage-appropriate systems and structure.

Learn strategies for selecting and working with manufacturing partners, the importance of defined technical roadmaps, and how to leverage early-phase data to ensure a competitive edge.

Stay tuned for part 3, where they will explore the business case for disciplined development, strong supply chains and robust partner agreements.

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• Email us at qualitygrind@medvacon.com

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Transcript

Ep 23 Navigating Cell & Gene Therapy: Accelerating Development and Innovation

Jessica Taylor: [00:00:00] This is the Quality Grind Podcast presented by Medvacon. Conversations that go beyond compliance. Sharing insights geared toward helping you navigate the everyday grind of regulated life science industries. Here are your hosts, Joe Toscano and Mike Kent.

Mike Kent: Well, we're off to a tremendous start in our conversation with Ray Kaczmarek around cell and gene therapy. To this point, we've focused on the people elements: characteristics of effective leadership, ways to strategize and evaluate what your team needs to be successful based on their performance, mindset, and where you are along your development path.

In part two, we'll dive into what that development process should look like, as well as strategies to both accelerate the journey and strengthen the case you're making for your [00:01:00] potential blockbuster new product. Here's a hint: it may involve ensuring those dreaded concepts of good documentation and highly integrous data. You know - good science!

So let's pick up the conversation with Ray as we begin our trek down the development path.

We get caught up in, there's a development process. A lot of people will talk about a development life cycle and mapping it out and, okay, you've got early development after research, and then you've got phase one, phase two, phase three, commercial and these expectations. 

What you're prescribing and really recommending is understand what your specific pathway looks like now, understanding it may change based on new information, new data, new things that happen, be open to understanding what that looks like and being [00:02:00] nimble to bob and weave around it. But there is no one map to get you from point A to point B.

Ray Kaczmarek: There's a, there's a template, right? Sure. And then I like to call it guidance. Guidance is a good template. I mean, but, it's guidance. Yes. Okay. See, so part of that is, scientific rationale is true scientific rationale. If science makes sense, science will prevail. It doesn't matter what people want to tell you, science will prevail.

Mike Kent: You just made a thousand PhDs really happy with, 

Joe Toscano: I thought it, 

was 2000... 

Mike Kent: 2 billion actually. 

Ray Kaczmarek: But it gets me back to the same thing as when you have a strategy of how you're doing something and the science is supporting what you're doing, it's very easy to explain because you can demonstrate it with science and data. It is, it's when you don't create the roadmap and understand where it is. 

So for me is if I can measure something and I can do it this way, and I know, [00:03:00] again, whether it's a platform or something like that, and I qualify it early, it makes it so much easier to do all my other work and it's gonna be much faster and much cleaner and much cheaper because now I'm not doing all these scale models and having to run three lots to show that this is there or do that I'm doing comparability protocols back to show that I'm actually comparative from one process to the other.

And again, this is where I think as I've seen more interactions like with the Food and Drug Administration where they're using more of the science, they're using more of the risk assessment, they're using more of that rationale.

So me as a CMC guy, understanding what that really looks like, yeah, I'm gonna drive people to do more science-based foundational pieces for testing and measuring earlier. Because the benefit for me in the Cell and Gene world is when I start getting to this backend and things can truly accelerate because I have great data, okay? I need that to allow me to make these changes very [00:04:00] quickly at the least amount of cost. But more importantly, I don't want to make four lots and three of them are going to, basically, they're gonna expire well before I could ever get them into a patient, right? And so that's all that money there is just wasted where I'd rather be able to make one good lot, test it, go to the Food and Drug Administration, then make those three lots and be able to use them in the patients that need it, right?

And so, it's a little different mindset in some ways. But that also means you have to have good data, you have to have science, and you have to think about your strategic pathway for how you're gonna file. And it may not be the same, but not every drug will be, and the need for it. 

And again, you may have accelerate approval, you may be an orphan indication. You could be rare. You could not have any of those and you could just be looking at a large market opportunity. But you look at it, I mean, it all started with with Car-Ts being different. [00:05:00] I'm treating one person with this dose, and it's a lot of money. But you know, if it works, that person gets cured of cancer or something. So, that's why, that's the wow side of it is, yeah, this stuff can really work. But we've also seen the same type of thing not work for everybody. So we don't quite know. But you know, that if there's a chance that somebody can cure cancer or they can be cancer free, you know, if it, if I could afford it, my, my family could afford it, I would take a shot. Absolutely. You can't put a, you can't put a value on somebody's time. 

So that's the way I look at it. And it's very difficult to understand how do you measure those things. But that's where I also believe that the industry, in my mind, is adapting to the fact that we've gotta have some flexibility because some of these things, really your body will naturally get rid of stuff. It'll chew up mRNA if it's free. It, there's [00:06:00] the safety profiles. You can get good safety profiles or you can see that there could be potential issues with oncogenes and other cancers and stuff can come out. We are seeing that and it's based on the types of technologies, delivery systems, how we're doing things and we're getting smarter.

But there were some early issues. There will be in this industry, because we don't know the human body, genomics, but it's there. 

Mike Kent: Understanding the science as we go has those risks.

Ray Kaczmarek: Yeah.

Joe Toscano: And, I think before, I like where it's going, but I want to kind of take a step back, and you said something critical before that is worth so repeating. And that is early stage, right, start the documentation process, systems, get the things in place that will make things accelerate quicker at later stages and be more cost effective.

Being a consulting company, I want to just put that on a big sign, do it early and get ahead of things. Because money's tight. You're, especially if you have a VC group that's coming in [00:07:00] and making an investment. And kind of a two part question I'm gonna come at you with here, but that's money well spent. Because what it'll save you down the road and the headaches and the time and the competitive advantage that it gives you is huge.

But what we find in dealing with a variety of executives and companies, especially those that are outside funded, so to speak, is they don't have an understanding of that. It's 'how quick can I develop it?', not understanding the implication that if it's not done correctly and documented well, right? And your systems are not put in place.

Yes. Money is, there's gonna be a lot spent early on in terms of investment, but do you have any idea of what it's gonna cost you later? There's no dollar figure that if you delay your launch and there is another competitive product out there and they've done it right. Coming in second place is never good in this industry...

Ray Kaczmarek: Yeah. 

Joe Toscano: ...unless you have a far superior product. So, how do you work with [00:08:00] leadership, the board and individuals that are saying, why do we want to spend more now versus addressing this later? Isn't this easy to address later? And we know it's not. 

Ray Kaczmarek: But there's two ways to answer the question. Only this question. There's one, only two, there's one. Well there's one, you convince them, and two, you just, you know, you create the budget and just do it. Right? But, the reality is this, right? As you start understanding, and some of the delivery systems and therapies just like potency assays, and some of those things that they get into now, It may take you a couple years to truly develop something that truly is what you need it to be, right? But some of these things will not take you that long. And if you're looking at it and you decided it's, it is helping your, it's, you can understand your platform because you know you've seen enough early data. The hardest part is do I want to spend a couple million dollars doing this type of stuff? And I really don't know if I'm gonna make it out of phase one with my safety studies. [00:09:00] Or am I really dosing it correctly in phase two? And then, you know, I get to the point where I want to figure out how to have things qualified and what I could have validated I do. But where do I spend that? 

And I think that's really gets back to how good is your science? And how good is the data coming out of your early phase studies, your non-human primate studies. The things coming in, are the things starting to match up when you start looking at your first safety studies, are you actually seeing other things coming out of that? That will start driving, in my mind, the discussion around what do you really want to try to get in place and how quickly. Because is there an accelerated pathway?

You know, a few years back there probably weren't a lot of companies asking that question. Is there an accelerated pathway to go, nowadays from here into now I'm gonna treat a patient and generate data as I go, right? Because there's not a lot of those patients and it's life-saving. Okay. 

You know what, the other thing to think about is a lot [00:10:00] of times small molecule, even vaccines, right. A lot of times they don't cure somebody. They either prevent or treat a symptom. A lot of either the cell side or the gene side is treating a disease, it's curing it, right? Your body, it becomes its own pharmacy and it eliminates the cancer. Or gives you something, a protein that you didn't have, that you didn't produce. And it's treating and it's actually curing the condition that you now have, right? 

So it, in my mind, that's what makes it super exciting. But us also makes it super scary of all the different things and variables. You can only control what you understand. And like I say, you have to embrace the 'reserve the right to get smarter', and always be looking at a piece. But early phase, there's really no right time, but there has to be a thought about gamble and understanding.

And I would look at it from this perspective. If I'm, if I [00:11:00] potentially have an offshoot of this technology into multiple different indications, the sooner I get that ability to qualify, test and understand, I just strengthen that entire bench. So if I'm looking at funding, if I'm looking at all these types of things, that actually becomes another advantage because I can look at my other pipeline things and know quickly whether I'm producing stuff for it well. And I'm saving costs in the secondary and tertiary program. So maybe I can start something if somebody will give me some additional funding to accelerate something within that. 

But I know a lot of people want to stay very focused these days. The last three years have been pretty brutal for a lot of people getting funding. But the reality is, as they can expand out, that does give you the ability to go quick. 

Joe Toscano: And, the reason I look at it that way, is, the people that are investing and spending money here, they have a pretty good idea that what they're purchasing or they're funding should be or else they [00:12:00] wouldn't be doing it. These are really smart people that have an eye for opportunities, and not only because of the business opportunity, because of the impact on health and people that it can have.

And that's where I go back to, if you believe in it that much, right? And you're spending the money to push it, acquire it, whatever the case may be in terms of moving it forward, that little bit of extra can propel you much further on that investment than what it would've if you were trying to save a little, if you know what I mean? 

Ray Kaczmarek: I don't want to be waiting for testing. In this industry, testing is key. It's not uncommon that submissions, your BLA has been delayed because you're waiting almost a year to get all your testing cleared. You know, we've seen that. We've seen that in approved drugs where things got delayed, but they were delayed because of testing, having to redo things, requalify, test different things, go through the OOS procedure because [00:13:00] the method wasn't... yeah... good. Those are the things that you, learn very quickly. The better off with your analytics you can be, early, the... obviously in my mind, it does shorten that time period. But again, it gives me the ability to do things on the Operations side because now I can do good comparability work. I've watched a, a group put some things together where they, where when they started doing some of the manufacturing, they created enough data in the manufacturing process to get rid of basically potency assays by using different methods on the floor because they did enough correlation to it. 

Wow. Okay. This is an early phase drug. This isn't an approved drug, but they've got history from the platform itself that's been used before in previous drugs. Okay, so as that platform developed, people took the time to do that and transfer over. The next products coming in on that platform will be able to do this, and the manufacturing of that is streamlined. So instead of waiting [00:14:00] four days for a potency assay, I know when I do my concentrations here because I have the equivalency to understand exactly what this test is telling me and why.

Joe & Mike: Right. 

Ray Kaczmarek: So, those are the things that, we're not there yet as an industry because we haven't grown up yet. But we are there as an industry because we've done this in other parts of industry. We just have not had the time and the money to do it on a platform that's had history in that regard, because not everything works the same every type of drug. But when you get it into a platform technology, they're gonna be very similar.

Mike Kent: It sounds like what you're prescribing is get as much out of that early work as you possibly can, understanding your risk and the platforms, what's available from a correlation standpoint. As a former bench chemist, I boil that down to my primary responsibility no matter what seat I'm on, on the bus. [00:15:00] Do good science. Good science means being rigorous about what I'm doing, understanding why I am doing it, not just doing it, and documenting the heck out of it. And using robust, scientifically sound methods to draw conclusions so that you can make well-informed decisions with a high degree of confidence that puts grease on those skids, yeah, if I got that. 

Ray Kaczmarek: I agree. Okay. I agree. And, one of these days, the whole cryo-preserving of people, is gonna be good. So then these earlier scientists that didn't write a lot of stuff... 

Joe Toscano: I thought we were there, already...

Ray Kaczmarek: Well, the guys that didn't write everything down, I want to just open that door and just turn them around. And I got this question, can you solve this problem for us? Well, to that, there's still a lot of, there's still a lot of that type of knowledge in, in industry across the board because of what we're talking about. 

But the reality is, the more effective you are at understanding the science and [00:16:00] documenting that rationale and being able to at least doing designs of experiments, not just I went to the lab and I did a mixing study, but actually just putting it into the notebook and just doing that. Now I can just generate a report from it later because it's been documented with good, at least good lab practices, and I did a mixing study on a product. Oh my God. I don't, I'm not in phase three manufacturing. I'm a guy going, hey, how long can I mix this for before I have product degradation issues? Or what's the temperature profile? You know, people forget about those little things. Those little things early on matter. And it doesn't take much to do, like you're saying. But if you just say, okay, we're gonna create these profiles. Just document them well. Then I create studies to go back and then I can increase that study and have a basis for understanding of what I want to do to make qualification. Yeah. And that's all people are asking for. 

There's a lot of ways to do that. And I'm not the most technical guy on that portion of it. I usually have people much smarter than [00:17:00] I am to be able to do that. But the reality is this is what they do well. And as we start thinking about how we accelerate industry, again, you're looking for those types of people that can train your junior leaders that are coming in and they're just gonna keep bringing your product up. So, we got opportunity. We've got a lot of opportunity in Cell & Gene. 

Joe Toscano: Absolutely. So, if a company has maybe not done the due diligence and they look like they have a promising product, what advice would you give, at the stage that they may be in, understanding every product's different, and things work a little differently. What are some of the things that they could start implementing now versus later when it's gonna be more cost prohibitive to go backwards. Yeah. What are some of the things they could, that if they're listening, they're like, oh my God, I don't know that we really have that as well documented or a process down. What are some of the things they could start doing now in order to start turning that around?

Ray Kaczmarek: Yeah. I think as I start looking at a technical roadmap, what I, what's the [00:18:00] characterization of my process and what is the things we would look at? 

I think it's important for the technical leaders and the regulatory leaders to actually talk, right? How am I gonna, what am I filing and how am I filing it? What does that really look like? And do I understand the product and its profiles and lines well enough to even know how to express the science, right? When they get together and the next thing you know, they start talking about what it is, and this person who is in Regulatory has been a virologist for 20 years and has a lot of experience with a lot of different things. Then starts to interact on how this will, you know, if it happens this way, it's much easier and the Clinic person says this, and the guy says, well, I can do that. Those are the first conversations, just creating this technical roadmap. 

And then within that, what are the key things we want to make sure we understand? And that's those studies, right? How does my product react? It doesn't take a lot to do, but it takes focus to do it, right, and put it [00:19:00] into a format that's usable later if I needed to do that. Or just create a simple protocol and just document what I'm going to do. And even if I don't have full acceptance criteria, I've documented a study and I have results of that study that I could use in the future as a basis of a qualification or a validation. Because at least I have data now and I could reference that.

So that's the type of stuff that I would say is just having a little foresight and saying, okay, what are the things we want to make sure we're generating as we go? I gotta ship samples. Well, okay, what things do I want to make sure I have today, right? When shipping the studies aren't, you know, you don't have to test all your products and do all this other stuff early. I got temp tails and all that other stuff. But when I start talking about the early design and what I have and what it is and what's going on, well, if I am shipping it from here to here and I'm having to do ID tests and everything else, why wouldn't I just run some stuff with it and write a study and determine if I'm having any sort of piece there, and I'm start generating [00:20:00] data on shipping. It's things like that is, can we or do we need to do that? Some of you don't have to do, eventually you will do it. And it's just, if you have it early on, because you're doing some of the work already, just put it in a format where you can write it as a report, put it into a study, put it into some sort of a protocol. 

And, again, creating the templates and asking the question of the roadmap is, do I have enough to get it from A, B and C? And then a lot of it is, if I'm gonna do some of the work, the additional qualification doesn't cost that much. If I'm already having a new product and I'm already having to test certain things and I'm always having to do a shipping thing early in my clinical stuff, the actual additional validation is not that much more. If you group that together and pack that on, a lot of times they'll just flip it from the other thing and test everything together if you needed to. 

Mike Kent: And then you've got at least a little bit of insight at the very worst of how to make that more formal study down the [00:21:00] line a little more honed in.

So as you talked about with other things earlier, you may do a little bit more upfront and earlier, but the benefits are you're not having to spend as much later on when you can allocate those funds elsewhere to accelerate. 

Ray Kaczmarek: And well, and sometimes it's not so much the expense, it's the time, right? If I've gotta do method feasibility and it takes me three months, four months to do all that and another three, four months to do validation because it's a cell-based assay or what have you, the earlier I can identify those things and the earlier I can do some of that work, and the earlier I can do that, it's less expensive in my mind. And earlier in phase it feels more expensive because I got less money. 

Joe Toscano: Right. 

Ray Kaczmarek: But when I'm losing time and it's been almost two years since I've manufactured my last clinical lot, and I've got a clinical trial that's ready to go and I'm trying to validate this method and I'm chasing that down, that's the money I'm losing because we couldn't, we didn't [00:22:00] think about it up here. And then how do I, how do I find a way to still do it cheaper?

And the other thing is you know, you've got partners, right? A lot of times these partners that you're working with, they understand your early phase, but they also understand that if I can partner with you and help you with costs, when you're in some of these levels, they be able to help you with costing. They may be able to help you with some of the sharing because they might be using some more junior people to do the feasibility and use it for training and stuff, as well. Okay. They may be doing those types of things to offset your costs because you're asking to do them little different order maybe or earlier. And it only benefits them because the better the method is that they're using and they know it's, they're there, it's validated, they're less worried about what's coming to them. And they're gonna be like, is this method right? What did you do wrong? Everybody's just scrutinizing everything about it. Well, it's now a qualified method. Okay. And I validated this and I've got this piece and I've got the matrix against it, and it's well within [00:23:00] this. Those are the things that help your partner.

So again, there's ways that I think partners help out companies if they're not doing all this work. If they've got their own labs, great. Because really it's materials that's driving, material and time drives the qualification. But if you use somebody else, then you're gonna be paying them for it. Yeah. 

But remember when you're expediting and validating a cell-based assay and you're trying to put it in front of four other clients, it's not cheap. Yeah. Okay. 

Mike Kent: And you can do an awful lot with a good, solid partner in parallel then to save time, which eventually puts you ahead. 

Ray Kaczmarek: And Analytics is always put on the side because it is a parallel path. If you don't pay attention to it, it becomes your critical path. It shouldn't really be on the critical path if you give it the attention and time early. But what you'll find, though, is a lot of times everybody [00:24:00] gets a case of how I manufacture it. It's gonna go in this reactor, it's gotta do this. If I'm not getting the results here. Well, if they're taking the time on the analytics to keep up, they go hand in hand. Like I say, the better my analytics are, the easier it is for me to do my analysis of my manufacturing steps, and accelerates my manufacturing. 

So, again, I know it's a little different thought than what some people say. It's not as, it's a little more variable in what I see and you know in the, especially on the gene side, it's a lot more variable, some of the test methods. But the reality is the value that comes out of it and understanding that for the product characterization as you go through and understanding how you are with looking your small scale model, comparing things back. It gives you that ability to have flex in design and scale. 

So again, I think it pays off in the end. Eventually maybe we'll do a paper and figure out what it actually, if it really does or doesn't. But, you know, [00:25:00] there's cost in time, there's cost in quality, there's cost in delays. And we start factoring that in. If you're minimizing the analytical doing that, then you're actually accelerating your manufacturing process because you're not waiting and you're not getting bad results out of analytical that you gotta go back and and validate. 

Mike Kent: It's not another thing you have to investigate if you see anomalies, because you know the method's sound.

Ray Kaczmarek: It's easy to say, difficult to do. You'll find that most things aren't very difficult to get through that process. And there will be two or three things. Companies will run pretty much even up to the BLA and still have things they're still trying to validate, because the methods are a little more complex and they're very unique to their product.

Again, we're gonna have samples. We're gonna look at that, we'll see how the science is going. There's a method that we have been using to allow us to understand that these should be somewhat comparable. But until I get this all [00:26:00] the way through, it's tough to get it across the finish line. But don't expect everything will be perfect in what we do. 

Joe Toscano: So, you've said the word a bunch of times and I think it's an important topic, right, and that's manufacturing. So, let's talk about manufacturing partners, right? Which you know they have to be selected early. They're gonna help you in regards to that process.

And as you know, one of the biggest issues in the industry, especially Cell and Gene Therapy, is picking that right partner to help you through it. 

<laughter>

Mike Kent: Here we go folks. Yeah, folks. Yeah, here we go. 

Joe Toscano: That's always a, a fun part. 

Ray Kaczmarek: Could go anywhere. 

Joe Toscano: Now listen, you know every product's gonna be different. The way to manufacture that process where that product's gonna be different, but kind of boiling it down as people are starting to get into this early phase and they're looking for that partnership and that group to work with that's so vitally important and can make or break the product depending on their capabilities. What are, from your perspective, [00:27:00] right, what are the things that people should be asking, looking for, you know, exploring, and we will talk about quality agreements secondarily, because that's another part of this, right?

Ray Kaczmarek: Have worked on a few of those. 

Joe Toscano: Yeah. So, before we even go there, what are some things that are helpful to people as they're trying to seek out a partner in this space, because that's such a critical component. 

Ray Kaczmarek: First you got to know what your product is, and what you have on your bench. Right? Okay. First you have to know who you are. And once you know who you are, the next question is, what exactly do you need? Okay. If you can get past those first two questions, you're 90% picking apart. And and a lot of times... 

Mike Kent: Sounds like dating advice to me. I thought we were talking cell and gene. I'm, I'm sorry.

Ray Kaczmarek: Life is, right? 

Mike Kent: It's the same. 

Ray Kaczmarek: I said everything in this industry's pretty much about the same. It's just got a little twist here and there. Right. right. 

But the reality is right, if you think about it is, you know, who am I and what do I have? And then who, what is it that I need? And then what [00:28:00] stages am I looking at? And then you are thrown another little thing that's there as it's around partnership and cost. And who can support what you need and timing that you need. 

But one of the big, big things is when you decide what you need, right, that's actually one of the most important steps. If you don't have certain technical expertise and you need your partner to have that expertise, you can't take a partner without it unless you're gonna go hire it. Okay? You have to make sure you understand that gap. 

All too often, somebody will go in and say, well, I expect this CDMO to have that person. Well, they may have one of them and they may able to work on that project, but you may not have that person dedicated to your program unless you paid to have that person dedicated to your program. Okay? You and six other people want that person working on your program, and they'll do the best to put them there. And they're not lying to you when they say, I got [00:29:00] somebody that will work on this and do that, and then maybe they're trying to hire a second or third one of them because of the types of contracts.

But really, do they have the technical expertise? Your partners need to have that expertise. And because not all gene or cell products are alike, right, and how they are, and some of them are sort of more combo these days than how they're doing this and delivering it. 

Yeah, and they're gonna get even more interesting as we think about it. You know, it does open for specialty. 

And the other thing when I look at that partner is I take a step back and then I say, okay, the next thing is, is how is that partner going to help me, not just from a learnings piece and being able to manufacture or even fill some of the spots until I can grow up to what I need to be. But it's also thinking about the next piece of are they gonna be here in two or three years when I need them to be. 

Mike Kent: Yes. Right. 

Ray Kaczmarek: And that's, [00:30:00] that's the thing when we start looking at some of the specialty groups, it's very difficult to understand how they're being funded, but they're, what's going into that and all that.

But technology's essential. And obviously don't want to build your entire manufacturing group and have to pay for their manufacturing group because you're the only client. And they, that's not a sustainable business model for them. But the reality is somebody's gotta pay for it. What are you really looking for?

So thinking about how those interactions are early on and really understanding that I think gets you at least to a short list of groups that you want to start having conversations with. It doesn't mean you can't take a small startup company because you can say, listen, um, I've got my cell line, I have this, I have that. I need somebody really just to manufacture this. And I need it so I can do it for IND-enabling stuff. So get whatever I need for this early piece. I can go to somebody who's brand [00:31:00] new, that might be the cheapest manufacturer for me. I just need to have enough understanding of the process, the information, whatever it is, and then make a decision whether I'll let them do phase one or not. And at that point, I gotta start thinking about the long term portion of my product. And are they gonna be able to grow up with you. 

Joe Toscano: Right. 

Ray Kaczmarek: It's not, you can go into a newer group and they'll grow with you a lot of times, especially if they've got a lot of different financial backing, or they're a company that's got multiple products and they're already showing the profitability, right? The reality is they'll probably be able to stay with you if you're forecasting and you're having those conversations and they've got a good foundation. 

But some of them, as we've seen, if we have a retraction in our industry, which we've had over the last couple years. I think you can look at Fierce Pharma as the readout of how many layoffs of the last two years are pretty much the same. Yeah. It's about the same number of companies, same number of large versus small, about the same number of people. The percentages are pretty [00:32:00] close. And you'd be thinking that you've got a big year with less money, more layoffs and all that. You think you're through it and you got another year just like it. 

Mike Kent: Not so much.

Ray Kaczmarek: So, what, what's this year going to bring to you? That's just gonna be between you and your investors and how you get there. But if you've got a drug product, money's there. But you're probably not gonna be able to do four or five. 

So that gets you back to what's your partner looking like? Because they're feeling that contraction as well, okay. How healthy are they? What's it look like? And then are they dedicated to the space that you're gonna be in? Because today they may say I want to be in gene therapy. And just like a few people that have been announced, and you can read it in the last, just in the last month, announced that they're getting out of gene therapy. There's just not enough work for them to make it profitable. Wow. So, you see that in, and that's what we have. 

So picking the partner for me first and foremost is knowing yourself and knowing what [00:33:00] you need. Is the partner gonna be able to give you what you need early on? Are they going to be a long-term strategic player? Are they just going to be somebody that's, you need to help you get through this space so I can get to the next funding round? So it is really where your company is, and having that. 

I'll also say, if you've got a good idea of what your company wants to be when it grows up at the end, I know I'm racing to do funding right now and just get them up, get my phase one clinical to raise more money to do that other piece, to make it for the next, to make it to the next. Yeah, but if you don't have an understanding of what you need to look like, picking a bad partner right now is only gonna get worse. 

Joe Toscano: And that's the biggest thing is, where we find a lot of people are challenged is they're not picking the right partner and then that just expedites the problems that are incurred. 

The other aspect of it is, even when picking the right partner, where we tend to see people fall short is not understanding it's still their responsibility. The other, they say, [00:34:00] oh hey, I can, there you go, thanks so much. 

Ray Kaczmarek: And we had, we had that conversation. We had that conversation in the office just today actually. - There you go. - Virtual office. And it was like, listen, if you're working with a partner, you can't expect them to be a technical expert on everything that you have. No, you just need to show them, this is how this was developed and this is, there's, here's your change control section.

And if you're not willing to have that conversation, then you're not respecting them as a partner. Because they're not making the leap because they don't know the science. And you're the sponsor, you're the owner. You just need to say this is how this actually works. Give them that piece. Give them the section. Have them make those changes because you ultimately are responsible for your process. They're gonna qualify what I give you, and they're gonna tell me where I've screwed things up. They're they're definitely gonna tell me that. 

Joe Toscano: And that's where they fall short, is I think companies [00:35:00] forget because they get a partner, and they say, oh, they could make it, right? They know exactly how to do it. Not understanding it's still your responsibility as the company, right? 

Ray Kaczmarek: We have to do the assessments and you have to make sure the clearance steps are there. We have all those types of things.

But I also need to arm that my partner with that type of an understanding. - Absolutely. - There's some things that, it just is what it is. As a therapeutic company, you're never gonna give everybody your secret sauces, because it's internal knowledge. But you know what, when I'm on a process, you need to give them what you're doing and why? Because if somebody knocks on the door in a commercial atmosphere, they're not asking whether I'm here. True. They're here. They're here to see you. Exactly. And what you know and what do you have. And then how good of oversight have I given them, what kind of information they have. Did they really understand the product well enough to manufacture it appropriately and know if there's actually a problem with it, right? So are we arming them with the right information? 

And that's, it's sort of hard to know early [00:36:00] on because you're, they're co-developing with you. So you, maybe you're assuming that they're learning your product, but if they're doing 15, 20 other clients, they're seeing a lot of different things. And maybe they're seeing things that help you, but they may have to see a lot of things that are irrelevant to what your product is. 

So that's where the conversation needs to be, is this is ours, this is how it's run, this is how we're doing it. And those decisions need to be made if you're gonna make those changes, in a somewhat of a joint manner. And I say somewhat. At the end of the day, you own the process and you own the product. And you're responsible for ensuring that the right types of things are being run. So you're going to, if you need to make a change to a process, then you need to make those changes. Because at the, if it's, if that's what's the difference between it failing and passing all the time, eventually it's gonna be called out in an evaluation and an audit because the data will be there. Right. If your partner isn't making that change and you're not looking to do that, that observation's on you. 

Joe Toscano: Right.[00:37:00] 

Ray Kaczmarek: Yeah. 

Mike Kent: Yeah. And that, oh, by the way, they're not going to, "Oh, our fault," as...

Ray Kaczmarek: No, they're not. 

Mike Kent: We refund your, we'll refund the purchase price. 

Ray Kaczmarek: They will hand you a bill for that for change. Because now there's a regulatory mandate to fix your process. So you have to think about it, because there's two ways to look at it. Oh, they screwed it up. They're not doing the annual product review sections and looking at how this process is running. Because that's some of the things you actually do contract for, that you expect them to be masters of that process and understand process variation.

But again, oversight. You know, if you see there's those types of things, are you actually addressing that? Yeah. They're gonna get a regulatory mandate to fix that and they're gonna charge you for it, because it's your product. And so that's them. You can head it off and do a cheap, or you can wait until it's being expedited. 

Mike Kent: We are at the halfway point of our visit with Ray Kaczmarek, having discussed the cell and gene therapy development process, [00:38:00] and considerations for selecting and working with a partner organization. 

Now, some key points from part two that stood out to me are having a solid understanding of what you're doing, why, and what enables you to be successful through your own development process is absolutely key. As Ray said, there's a template and guidance for this roadmap, but ultimately, we have to define it for our own program and then be wise enough to recognize and leverage the parallel opportunities that exist to create a significant competitive advantage and accelerate our timelines. 

We also discussed ways to determine if additional expertise or a full on partner is a good choice, and provided some points to consider for selecting and building a strong relationship with that partner.

In part three, we'll dive into the business case for disciplined development, [00:39:00] strong supply chains, and well-defined quality agreements that don't have to be a drudgery. Bottom line? It's about setting your organization up for success on all fronts. 

So join us for that and more as we continue our conversation with Ray Kaczmarek around Cell and Gene Therapy, next time, here on The Grind.

Joe Toscano: If Medvacon can help you and your organization, we're happy to do so. We specialize in the following areas: Quality and Compliance, Validation and Qualification Services, Project Management, Tech Transfers, General and Specialized Training Programs, Engineering Services, and Talent Acquisition. If you have general questions as well, feel free to give us a call at any time.

We can easily be reached at 833 633 8226 or via our website at www.medvacon.com. Thanks so much, and we look forward to speaking with you. 

Jessica Taylor: Thank you for listening to the Quality Grind Podcast presented by Medvacon. [00:40:00] To learn more or to hear additional episodes, visit us at www.medvacon.com.