The International Society for Cellular Therapy (ISCT) is a global society of clinicians, regulators, technologists, and industry partners with a shared mission to drive the translation of all cell and gene (CGT) therapies for the benefit of patients worldwide. The ISCT 2023 Annual Meeting took place in Paris, France from May 31 to June 3 2023. DDW’s Megan Thomas heard from attendees about key trends in the sector. First, the importance of cell collections. Next, attendees discuss the trend of allo vs auto. Then, new generation MSCs and the future regulatory changes. Finally, this article covers the CGT trends when it comes to redefining manufacturing.
Manufacturing processes are among the bottlenecks of CGT wider use. Standardisation, GMP processes and cost all need to be improved, says Carole Nicco, Chief Scientific Officer of BioSenic. She adds: “BioSenic is in the process of establishing partnerships and funding with companies in the Walloon region in order to take a multidisciplinary approach. Our partners are leading companies (Conveyxo, Exo Biologics, Livedrop, Genflow Biosciences, Orgenesis, Theracell Advanced Biotechnology, Cylix Group) for each step of the production of ATMPs, which will then be developed and clinically evaluated by BioSenic. Our goal is to bring these innovative treatments to patients as quickly as possible and we are doing everything we can to achieve this.”
The manufacturing of complex living medicines is extremely challenging and currently proving to be a bottleneck for our ability to meet patient demand, says Lindsey Clarke, VP Commercial at MicrofluidX. “Fortunately, innovation is happening rapidly across the sector to address a multitude of today’s manufacturing challenges, but we need better ways to adopt these improvements faster,” she adds.
Clarke thinks that data and digitisation are the keys to unlocking manufacturing. She said: “Yet, whilst we live in a digital era, we are yet to be fully empowered by the tools of it. But I do think we know what it is that we need – it’s deep biological understanding of the patient, product and process, right through from early R&D to long-term patient follow-up, in large datasets, with the ability to interrogate, learn and predict from them. And, if we find a way to do this, then not only can we bridge to manufacturing improvements faster, we will also be in a position to control for and adapt to the intrinsic biological variability of the cells in our therapies.”
Becky Cap, SVP, Business Development, Advanced Therapies at BioBridge Global, said: “When we talk about manufacturing, we tend to focus on the clean room time or the active processing time from a regulatory standpoint. That makes sense. From a business and operations standpoint – and impact to the patient – we really need to consider the time from patient identification material collection processing testing, and treatment – and all the logistics and transport costs associated. We are using our continuum of service from collection to delivery to rethink how manufacturing gets done in ways that increase patient access and reduce cost.”
ScaleReady’s Global Director of Commercial Operations, Josh Ludwig, weighed in: “Because cell therapy manufacturing today lacks industry-wide standardisation, process development for clinical scale-up often means laboriously adapting production to new equipment. It’s also a one-way ticket: optimising processes based on data gleaned in the clinic means either wasteful large-batch testing, or jumping backwards to small batches and redoing process development, the latter is almost impossible to get right. Either route is expensive, complex and time-consuming.”
He outlines how new approaches are focused on simplifying processes by leveraging technology that can be easily scaled from research-grade production to large-batch manufacturing. He concludes: “This allows for both rapid scale-up and critically scale-down (previously this was not possible), with maximum flexibility and cost efficiency.”
According to Ludek Sojka, CEO of SCTbio, the development of CGTs has vastly outpaced the ability of the sector to supply these therapies to patients, as well as for society to pay for them. He said: “The focus so far has therefore been on the ability to cure the disease, not the patient. Also, to reverse the spiraling costs of CGTs, there must be an entire redefinition on the production and delivery of therapies to enable wider patient access.”
He thinks that the simplest solution to redefine CGT manufacturing involves the experience and expertise of the CDMO and its teams. He continued: “Developing therapies at the cellular level still remains the most advanced field of medicine to date. Manufacturing safe, clinical-grade cell-based therapies and retrovirus vectors in one place takes experience. SCTbio has operated for more than a decade, producing over 2,000 cGMP batches of cell-based therapies. This experience has resulted in very low batch failure rates, which has a considerable reduction in the cost of production. This experience also involves technology transfers, for therapies across the clinical development stages and for developers based across global regions, from the US, through Europe and to China. SCTbio’s view is that experience, working with a range of therapies and different organisations, is important in enabling innovation alongside high success rates.”
He adds that one of the largest contributions to the high production costs of CGTs is the high skill and qualification levels required to manufacture these advanced therapies. He concluded: “SCTbio is based in Czechia, which provides access to highly skilled central European technicians with a number of competitive advantages. Furthermore, the ability of the staff at all levels in an organisation to communicate both ways with clients – asking the right questions and having the forethought to listen carefully to the answers – sounds simple but is critical in manufacturing.”
Natalia Elizalde, Chief Business Development Officer at ViveBiotech, commented: “As a GMP CDMO, VIVEbiotech are continually redefining lentiviral vector manufacturing though our Innovation and Bioprocess development departments. Our aim as a company is to optimise our well-established manufacturing platform to obtain the higher titre and the most pure lentiviral vector in compliance with FDA and EMA regulations. We focus our effort on both lentiviral vector tire and purity enhancement as these two factors have a direct impact on the functionality of the vectors both for ex vivo and in vivo use.”
As a company, ViveBiotech focuses on scalable, regulatory compliant and cost-effective lentiviral vectors and as such, are working on different aspects such as producer cell line and construct optimisation, transfection process adaptation, downstream process optimisation, and scale-up to commercial scale including automatic fill and finish – among others. Elizalde concluded: “By improving and streamlining manufacturing processes, developing more scalable platforms, implementing rigorous quality control measures, fostering collaboration, and ensuring internationally harmonised regulatory compliance we would be able to enhance efficiency, scalability, and quality assurance in lentiviral vector production. This would help meet the growing demands of viral vectors and alleviate the currently existing bottleneck, thus enabling more patients to have access to these curative therapies.”