Fierce Pharma Sits Down With Catalent

Sponsored by: Catalent

As manufacturers continue to focus on growth, the strategies involved in scaling a pharmaceutical development program top the list of concerns. Jeremy Trochu, Vice President and General Manager of Pharmaceutical Development Services at Catalent, recently sat down with Fierce Life Sciences to detail the factors to consider when planning the scale-up of a development program.

In this interview with Fierce Life Sciences Head of Conference Programming Zohaib Sheikh, Trochu discussed potential problems that can arise during tech transfer, and what Catalent has done operationally to support projects as they scale up. He also outlines the advantages of working across a network of sites and discusses when and why a project would transfer from site to site.

Watch the full interview with Jeremy Trochu above. To learn more about Catalent’s integrated solution from development to commercialization click here.


Zohaib Sheikh:

Hi, everyone. My name is Zohaib Sheikh. I'm the head of programming for Fierce Life Sciences, and we're excited to have, on the line, Jeremie Trochu, Vice-President and General Manager of Pharmaceutical Development Services from Catalent. How are you today, Jeremie?

Jeremie Trochu:

I'm good. How are you? Thanks for having me.

Zohaib Sheikh:

Great. Yeah, of course. Glad to be speaking with you and chatting with you today. So let's jump right into things. So, what factors should be considered when planning for scale-up of your development program?

Jeremie Trochu:

Well, actually there's a lot of factors. This is a pretty daunting endeavor. But if you want to emphasize just a few ones, clearly you want to have a good sense of where your formulation's at, what equipment train and scale you're considering for the next space, depending on when you're doing that scale-up. I mean, [inaudible 00:01:01] to be informing a lot of decisions. So having a good sense of that, or being able to articulate some of the needs and challenges with the partner you'd select to help you do that scale-up, that'd be critical.

Jeremie Trochu:

Similarly, I think having a good understanding of the development history and making sure that people that worked on the very early steps, even preclinical, anything around execute compatibility, [inaudible 00:01:29] characterization... I mean, all those data points are going to help you define and design the right scale-up programming process. So what we tend to recommend is, as much as possible, connect with the individuals that were involved earlier in the development process, sometimes not doable, physical, because the molecule, the program has changed hands over the years. And if we've be able, in our case, to support that program... maybe one of the other sites was in the network... We'll make sure to bring up and involve those individuals, also, early, as part of the discussions.

Zohaib Sheikh:

Great. So what are potential problems that could arise during tech transfer?

Jeremie Trochu:

Well, again, numerous ones. I think you got to start with, conversely, to formulation. Often in the steps, you're going to think about, do I have the right formulation? Is there, I would say, optimization work to be done? Maybe some true reformulation? But in general, I think one of the main trends is going to be around the scale-up in terms of... You used to have, maybe, go first to human, a manual capsule-fill process, maybe 10,000 units. And now suddenly you're looking at, I mean, 100,000 in some form of automated fashion. So your scale-up and your planning to think about the equipment train... Again, is it a process that is robust enough to accommodate that? If there's going to be issues because you were on X equipment train and now you're going to a different one?

Jeremie Trochu:

So that is something that we see often as real hurdles. Same thing with the formulation. Is it going, again, be accommodated to the new scale and the new requirements that you're looking for in that process? Also, and not to be underestimated, the methods and all the analytical work and the [inaudible 00:03:27] method then needs to be developed. Often you're going to have some... I'll call it basic and just to get going to have a proof of concept. But now you need to have something that will ultimately need to be validated and so requires a little more work. And sometimes you need to go back to the drawing board.

Jeremie Trochu:

And then the last piece we're seeing more and more, if you think about the oncology products and indications that are out there in the pipelines, higher potency of the molecules and the programs you have to deal with. Therefore, containment requirements are also critical, and it's one thing to handle high-potency compounds in the GLP space, at small quantity. Then, when you get into the GMP space and making sure that you have the right strategy to contain it, sometime that has implication on the actual equipment you're going to use. And you're going to have to do a time-out and do an engineering design step on how you're going to have the right strategy to handle those compounds.

Jeremie Trochu:

So again, just outlined a few, but that's the fun of development. You will encounter a lot of challenges. It's about the planning and having a overarching and holistic vision of what all those different work streams that need to be put in place to have a successful scale-up.

Zohaib Sheikh:

So what steps has Catalent taken operationally to support projects as they scale-up?

Jeremie Trochu:

Well, as you know, we've been in the space for a while. So we've dealt with situations, challenges like that, for many years. But frankly, I think, historically, we would apply... Call it good project and program management, maybe a delicate way of coordinating brute force when you're trying to tech transfer a molecule, either from the outside or scale-up the molecule program from one early development site to one of our commercial-ready site. What we've learned, especially over the last three years, and we've had a more deliberate approach, is to really try to understand what are the gaps that are contributing to, again, those challenges. And what are the opportunities to reduce cycle time, compress those timelines, save API, [inaudible 00:05:40] this transition from one site to another?

Jeremie Trochu:

And so, we've tasked our teams, cross-functional from formulation [inaudible 00:05:47], engineering, manufacturing, EHS, procurement, to really start to harmonize a lot of those work streams. So it can be as simple as making sure that the excipients and the raw material you're sourcing are going to be the same from one site to another, because that's going to help a lot in your initial activities. You're going to have to organize your equipment trains, so making sure that you may have that particular piece of equipment for that particular capability at that clinical scale. And then it becomes even more phase-appropriate to get into phase 2, phase 3, and then ultimately can support commercial-supply quantities.

Jeremie Trochu:

Same thing in the lab. Sometimes you will have methods [inaudible 00:06:31] on UPLCs and some that are on HPLCs. But, if you don't have the mirroring equipment between your sites, you're going to lose a necessary common. So, a lot, simple, pragmatic, but that takes a lot of homework in the background, to harmonize some of the investment, but also harmonize, as I mentioned earlier, about [inaudible 00:06:51] strategies. So making sure that, when you're doing your early stage development, you have an eye towards planning when it's going to scale-up, when it's going to go transferring to another site. What should I start planning? And therefore, having that phase-appropriate, I would say, objective and guidance up front helps to also make sure that, okay, you don't forget that soon you're going to be at the next stage. And then, at some point, you're also going to be able to launch and supply commercially, which has other constraints.

Jeremie Trochu:

So we've put that in place, formally, over the two years. And we're very pleased to be in the process of rolling out that offering, [inaudible 00:07:34] called One Express Solution, which really is about having formalized those best practices and processes that have been harmonized with dedicated resource, dedicated program management. And very pleased to report that, in the last year alone, we've done over 12 transfers, such as a scale-up between our early development sites and our larger clinical sites and now, ultimately, commercial. So very excited about what we can offer to our clients.

Zohaib Sheikh:

Sounds great. Are there advantages to working across a network of sites?

Jeremie Trochu:

Yeah, absolutely. I'm a big believer that... I think you mentioned that earlier. Leveraging phase-appropriate expertise and skill sets from the network that we can offer different vendors out there is critical. The needs that a client will have for its program earlier, preclinical, to get to the clinic, is going to be very different than you've got to scale-up, industrialize your process and be ready for a clinical launch. And it does translate to how a site in a facility is going to operate. If you can be in that early state development focus, you're going to have more flexible processes. You're going to be able to probably move a little faster. When you go into a commercial site set-up, well, by definition, there's going to be a little more rigidity and an infrastructure that needs to be taken into consideration because you have to meet the right regulatory requirements and the quality standards to be able to successfully launch your product.

Jeremie Trochu:

So being able to offer best of both worlds is, I think, something that is critical. And again, based on the success we've had, we feel that our clients and clients out there do value that phase-appropriate approach, while, at the same time, making sure that there's seamless transition when their program moves from one site to another, with the coordinated program management and this set of organized processes and investment we've made over the last couple of years.

Zohaib Sheikh:

Great. Can you give us any examples of when and why a project would transfer from site to site?

Jeremie Trochu:

Again, different reasons. I can name a few. Definitely, when you're phase-based, so you get into the next phase, different clinical trial to consider. That can be a trigger for one client to think of maybe going to a different site and scaling up. That kind of thing... if the quantity is required, and again, that'll tie to your trial. But sometimes, just as part of the strategy, additional indication, different clinical trial strategy. Different geographical strategy may be a trigger.

Jeremie Trochu:

Often, also, and that's more challenging, is when you have a formulation issue. And you're running into problems or process developability issue, and you need to rethink on, okay, is that the right site that's going to help me take it to the next level? Is that the right process and equipment train that is going to support the scale-up of my program?

Jeremie Trochu:

So those are examples that will be the trigger points. But again, you tend to see really... I don't know if there's a perfect sweet spot, but it's going to be around that phase 2, phase 2b, which sometimes gets much blurred, now, with a lot of auxiliary pathways for development. But that's when you need to think about that commercial launch readiness, that robustness of your process. And this is when, again, we tend to recommend and accompany our existing clients in our early-development network to consider going to our larger-scale commercial supply sites. And all that's when we tend to see a lot of programs where clients say, "Hey, can you help me address this challenge and help me be ready for commercial launch?"

Zohaib Sheikh:

Great. Well, very great insights. And we appreciate you taking the time to speak with us today, Jeremie.

Jeremie Trochu:

Oh, thank you. Thank you for having me.