Advancing Revolutionary Therapies

The Logistics of a Clinical Study Scale-up

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Scaling up from phase 1 to global phase II/III trials to beyond marketing approval has several implications on a sponsor’s commercial strategy. Hear from Rachel Smith, Portfolio Director for Veristat, as she uses our recent work with a biotech company to illustrate the importance of a comprehensive shipping and traceability strategy, tight management of the patient journey, and adoption of a well-conceived protocol and process documentation to support the commercialization strategy.

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Bringing a cell or gene therapy to market is an art here. Vera stat thought leaders, as they draw on their specialized expertise to offer insight on timely relevant clinical development topics. Welcome to,

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Uh, podcasts advancing revolutionary therapies. The podcast presented by the center for excellence for cell and gene therapies by barista. My name is Rachel Smith. I'm a portfolio director here at barista, working with our clients in and gene therapies, providing operational excellence from strategic consulting to clinical trials. And post-marketing commitments today. I'll be discussing the topic, how we manage the logistics of scale-up. You may have already listened to my previous podcast, common pitfalls to avoid when planning your gene therapy study, where I gave a high level view of common issues we've come across on gene therapy programs. One of the topics I touched on was logistics. And today we're going to delve into that in a bit more detail. The objective of this podcast is to talk about scaling up from your early phase to global phase three trials in preparation for commercialization frequently, we start our cell or gene therapy studies with proof of concept and safety evaluation in mind, but we don't consider at this early stage how the project is going to be commercialized. Post-market. Now this makes sense, right? We want to know that the product works and we want to know it's safe before we put the investment in. But when we're talking about advanced therapies, the number of studies within the development program can be much reduced. For example, you may have a program with just two or three studies before submitting a VLA to in the U S or MAA and other markets. And actually commercialization is a significant piece of the puzzle when planning your marketing submissions and should be demonstrated within your trials. Regulators want to know how the product will be managed within each region. If it's approved, in some cases, this can be relatively straightforward. An allogeneic cell therapy with a starting material from an established validated cell bank that can be cryopreserved shipped from a central manufacturing site, and simply infused into a patient is much easier to plan for than say an autologous gene therapy where freshly collected cells need to be shipped across country or even internationally for manufacture that must remain viable in transit. Today, I'm going to talk about the latter in the form of a case study, where we supported our client with this exact issue. We had a complex program where an academic center had developed an autologous ex vivo gene therapy and manufactured the product in early trials, an onsite GMP facility. The product was subsequently licensed by a biotech with the view to market the product in the U S and the EU. This would only be commercially viable if patient's cells could be collected by local transplant teams or approved centers globally and shipped to and manufactured at a central GMP facility with the finished product being returned for local administration to the patient in a consistent manner. So a phase three trial was needed to be able to test this process as well as supporting the CMC modules for the marketing suspicions and product labeling. None of the parties involved actually had experienced with scale up or commercialization. So this is where we stepped in very stats, expert team supported every aspect of the phase three strategy from planning to delivery. Our first step was to work with the sponsor and chosen sites to establish what the local processes were for south collection. In this case, we were allowance us with light started by bone harvest or by apheresis. So we needed to understand how that was done and the differences between the size. This allowed us to identify where routine clinical practice into later travel requirements, as well as highlighting any process gaps that we needed to fill and identifying the teams involved to actually be responsible for performing the cell collection and processing steps up until the point of handover to the courier. We then needed to support the setup of a global courier, selecting someone who was experienced in the shipment of transplant organs across the world as heparin stabilized harvest, the cells would need to be transported in the worst case from the U S west coast to mainland Europe within 48 hours to guarantee viability this required a truly tailored approach. As the flying itself is 12 hours. The cells were physically transported by a single person from the hospital on a commercial flight on the evening of the cell collection for personal delivery to the GMV P facility. The following morning, as you can imagine, the logistics of this were extremely complex and required expert planning from our teams here at FareStart, particularly when thinking about the bone marrow cell collection piece for this surgical slots had to be scheduled as late in the day as possible. So ourselves could be as fresh as possible, but with enough time to process the cells for transport on that evenings overnight flight, the courier had to be on site ready for the cells before the surgery could begin and to add complexity, local regulations meant that all routine surgeries have priority over research surgical slots and slots could be moved at the last minute, quite rightly in the event of emergency surgeries, we also had to be weather people. So we had to monitor weather events to ensure that the risk of flight cancellations was minimized. If a Stone's forecast surgical slot just had to be moved, it's not ethical to collect cells that may not reach the GMP facility on time from a patient, and then have to reharvest. Our team had to coordinate every single function from the Korea to the sponsor teams, to the manufacturing teams, surgical teams, lab teams, and everyone in between, right down to the minute in what was an orchestral feeds by comparison, the returnship men of the cryopreserved gene therapy product from Europe to the U S and actual patient treatment. It was a walk in the park, as anyone knows in our industry, if it's not written down, it didn't happen. So alongside identifying the strategy and logistical steps, very that supported the development of the accompanying process documentation, including checklists to ensure that everything was checked, checked, and triple checked each step of the way, the most critical of these documents was a vein to vein traceability protocol. And on my earlier podcast, I talked about the importance of tracing every single cell. The traceability protocol truly allowed us to track eight each cell from patient to Europe and back to patient again, as well as implementing integrity checks at each stage. So making sure that the product was undamaged temperature controlled and not tampered with on its way to the manufacturing center and on its way back. This traceability protocol also included the critical data that we needed to form the CMC product batch records at both collection and administration points. So for example, administration, we were capturing time of Thor, expiry time thought, product infusion start and stop times. And the volume infused as soon as a super critical data points. Ultimately, the processes and documentation we put in place was adopted by a client for all of that programs. And this fed into that overall commercial strategy to get more of these types of products to market with a global patient rage. Great for the patients, from my perspective, this is one of the most logistically challenging programs I've worked on in my career. The only thing that would have made it more complex is if the route of administration was something like brain surgery. Well, we've done that too. I'm hoping to discuss that feature podcast series. So keep an ear out, brought this podcast. I intended to give you a bit of a flavor of how truly complex moving from early phase to commercialization can be from an operation perspective. So that's without truly touching on the CMC strategy piece thermostat is managed clinical trials for the first gene therapy to be approved in the Western world. And as trailblazers, we continue to be actively involved at the cutting edge itself in gene field. We encourage you to listen to future episodes of this podcast. As we delve deeper into some of these issues and other important topics in the space. I hope that this has been valuable to you. Please reach out to our experts here and through the links available on the first site website. Should you have any questions? And we'll be back talking to you diary saying,

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