Learning From Experience: Navigating Cell & Gene Therapy Development Challenges with Productive CDMO Partnerships

To start with, please could you introduce yourself?

I’m Andy Lewin and I’m the Chief Commercial Officer at Pluri CDMO.

Can you discuss the key manufacturing challenges in cell and gene therapy development that you’ve encountered over your extensive career, and how these challenges have evolved?

I think in the manufacture of biopharmaceuticals always and forever you’ve got three big competing forces. One of them is cost, one of them is quality, and the other one is time.

I think everybody wants to get where they want to get to for as less money as possible, of course, and also, they want to make products that aren’t prohibitively expensive. So, economy of scale, cost of goods are vitally important, and you hear that every week at any conference on cell and gene therapy particularly, because right now, all of our products are rather expensive. So that’s something that’s a big challenge for us in cell and gene.

How are you enjoying this Q&A? Let us know your thoughts, here >>

Similarly, everyone wants to go as fast as possible, but you can’t because you need to make sure that you take care of quality. Again, in an emerging field like cell and gene, quality is probably technically one of the most difficult areas because you’ve got an enormous diversity of product types now.

Everybody’s to some extent feeling their way. What are the important considerations in the manufacture of whatever it is you’re making? It could be a CAR -T, it could be a cell therapy that’s just an unmodified stem cell, it could be an iPSC-based thing, it could be an exosome, or it could be whatever, and those are all very big challenges. I think everyone in the industry is troubled by those things and is putting their expertise into it.

I’m lucky, because my colleagues have some considerable experience in that. Pluri is a company that has been around for 20 years. We’ve put products into clinical trials around the world, we have experience in dealing with those issues, a scale of quality and of time as well, trying to go as fast as possible.

In your experience, how crucial is an early partnership with a CDMO in the success of advanced therapy products?

I think the key word there is ‘partnership’. Working with a CDMO, you’re looking at engaging with a team of people who are involved in clinical trials, who have perhaps manufactured the same type of product that you’re looking to manufacture, taking it into clinical trials and perhaps launching it onto the market. So, the partnership aspect is vital.

You’re enlarging your team as a company. So, the therapeutic inventing company, the innovative company, is getting a bigger team on board because it’s engaging with a CDMO.

Is that team engaged with what you’re trying to do? Are they bought into your goals? Are they really, truly part of your team? Or are they just transactional, arms-length people? I don’t think the answer is obvious. Of course, what you want is a tight, motivated team and a good partnership between the two organizations.

When one is outsourcing, one is basically spending money to get not just manufacturing capacity, but expertise, experience, and things that you haven’t already got in your own company.

How can proactive CDMO partners support developers in ‘planning for success’?

Planning for success, in my eyes, means beginning with the end in mind, thinking about where you actually want to end up, and probably, mostly, that isn’t just the next clinical trial. Most of the time, it’s what we’re doing here is we’re making a product that is going to cure people, and we want it to be on the market as quickly as possible, treating as many people as possible in all the jurisdictions we can.

That’s not just a commercial end for a product development path, but it’s also a sort of ethical and ideological end. That’s what we’re all in it for, and I think, therefore, when you’re engaging with manufacturing sensibly, you think about the longer term as well as the short term.

You think about the end game as well as the next challenge, and I think, again, what we can bring to the game at Pluri, is that we’ve manufactured very early-stage products, we’ve also manufactured Phase III, readiness for commercial products, and so we can bring some of that longer range perspective.

I think it’s very important to think about the endgame, because you may need to manufacture an awful lot of your product. For example, for Phase III in commercial, it seems an awful large amount compared to what you need now for the short-term Phase I, but it’s still going to happen if you win, if you get where you want to get to. So, you better start thinking about it soon and you better engage with the technology and with the facilities and with the people who can take you there.

What other qualities should developers look for in a CDMO to ensure a successful partnership throughout the cell and gene therapy development process?

In this space, it’s very, very helpful for CDMOs to be able to offer a broad range of services from process development, early analytical development, product development for preclinical and early phase clinical studies, and then to be able to take that forward into Phase II and Phase III and help with and support and know how to do things like process analytical validation, process characterization, because those are big chunks of work and they need expertise, they need regulatory understanding.

How does a motivated and dedicated team within a CDMO contribute to the overall success and story of a cell and gene therapy product? How do team dynamics play a crucial role?

I think it’s important. I think that where I’ve seen the most productive interactions between CDMO and client is when the team at the CDMO is heavily invested in the success of the product, and that happens quite often, actually. It certainly happens in our company, and it’s certainly happening in companies that I’ve worked in before, where there’s a genuine excitement and ownership from the CDMO team interacting with the customer team, forming one whole thing and saying, “let’s get this done and let’s make this work.”

That’s when things get really exciting, because you’re really combining the expertise of both groups and everyone’s trying to get the product over the line, and honestly, that’s an ideal, and it happens, and it’s nice, and I think it’s vital.

As developers enter clinical trials and early phases, what strategies and preparations do you recommend to ensure success in these critical stages of cell and gene therapy development?

I think, generally, coming back to what I said earlier, real deep engagement with your CDMO. At Pluri, we’ve been able to develop products, take them through clinical trials and in different jurisdictions, engage with different regulatory authorities, develop different assays, develop strategies for formulation, develop formulations, and we have a huge track record of experience and expertise.

If the clients that come to us and tap into that, benefit from it, they get a lot more than they paid for, frankly, in terms of wisdom and expertise and history and experience, that’s the key thing. Get in there, engage, benefit from your partner. Then you’re using everything that you’re paying for and everything that you’re working with.

Can you share insights into the evolving regulatory landscape for cell and gene therapies (or perhaps how an evolving landscape may present challenges for therapeutic developers), and offer advice on navigating regulatory challenges effectively?

We’re in an emerging field, so what we see is that regulatory authorities are genuinely challenged and they do their very best to understand what is coming at them from the new products that we’re developing in the cell and gene space.

There is an enormous variety. Even within Pluri, we can manufacture stem cells, iPSCs, CAR-Ts, exosomes…There’s an enormous amount of innovation in the space at the moment.

At the moment we’re in an environment where frankly, the regulators are being tremendously helpful, as much as they can be, to try and help area the stream forward and I think that’s to be welcomed, but that puts the responsibility of us all to try and manage things.

Fortunately, we’ve had some experience in dealing with regulators in America, in Europe, in Korea, in Japan, in Australia, and we’ve delivered clinical trial materials to all those locations, and that’s fantastic.

So, we’ve got that experience, and we continue to develop it as we go forward.

Looking ahead, what trends and advancements do you foresee in the field of cell and gene therapy development, and how should developers and CDMOs prepare to stay ahead of these developments?

I think scale is very important. I think scale is really critical, because I think scale is one of the keys, and a big key, to reducing costs of manufacturing.

In our lives, we know that the things that are manufactured at huge enormous industrial scale are the things that are cheap, and we also know that the things that are manufactured for us and us alone are very expensive.

What we face in this field is that autologous products that are manufactured for a patient are very expensive, and that’s important and they’re very effective, which is great, but we need to think about how we can develop products that are lower cost and they’re manufactured on a bigger scale.

That’s something that’s hugely important for our industry because otherwise we will never be able to get the levels of patient access that we really want, and we will always struggle with pricing and reimbursement, and all of all those lovely things that people talk about.

We in manufacturing have a role to play in helping out our customers reduce costs of these medicines, and the way we’re going to do that is by being able to offer scale-up solutions that are viable for autologous products, and also for allogeneic products in different ways. As technology developers we bear a responsibility, and as innovators in our field, which is manufacturing, we bear a responsibility.

At Pluri, we have our own proprietary platform for cell expansion and cell harvesting which allows us to produce stem cells and other cell types, adherent cells, at very high efficiency, and at lower cost. Other technologies we have had to develop because other things weren’t available, and so we’ve pioneered that and we’re proud of that.

I think the whole field has to do that kind of thing. I think that’s something that’s going to be the next several years of activity for all of us in manufacturing.

Finally, what gets you out of bed in the morning? Why cell and gene therapy?

The best thing in this role, in my career, has been being part of pharmaceutical product development where it’s been successful, and where we’ve got products on the market.

I’m lucky enough, now that I’m old enough and had a long enough career, I’m lucky enough to have seen that happen a couple or 3 times in my career, and that is enormously rewarding. I think that everyone in this field is similarly minded. Actually, I think it’s the big motivation.

The big motivation is to see product success and to see people getting the benefits of treatments that you’ve had something to do with, even if that part was pretty small. It’s an immensely rewarding experience and I hope to see it again.

This interview was produced in partnership with Pluri.