The future of cell therapy: scaling production for global reach

The cell therapy field is experiencing a period of rapid growth and innovation, with new treatments for previously intractable diseases emerging regularly. This expansion presents significant opportunities for Contract Development and Manufacturing Organisations (CDMOs) that can navigate the complexities of cell-based medicine production. To gain insight into this dynamic landscape, we spoke with Andy Lewin, Chief Commercial Officer for PluriCDMO – a leading CDMO specialising in cell therapy development and commercialisation.

A comprehensive approach to cell therapy development

PluriCDMO brings over two decades of experience to the table, offering a comprehensive suite of services designed to accelerate the development and commercialisation of high-quality cell therapy products. “At PluriCDMO we have over 20 years’ experience in developing and manufacturing cell therapies, and that experience and knowledge informs everything we do for our customers,” Lewin explained. Their services span the entire process, from process and analytical method development, including process and assay validation, to early-stage clinical manufacture in clean rooms, Phase II and Phase III clinical trial manufacture, and commercial supply. They also provide drug product and drug substance manufacture, QC and QA support, and a sophisticated shipping and distribution service, enabling them to support multi-centre clinical trials or commercial supply worldwide. Importantly, PluriCDMO adheres to international regulatory standards, meeting the requirements of agencies like the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and Pharmaceuticals and Medical Devices Agency (PMDA).

A key differentiator for PluriCDMO is their proprietary, scalable manufacturing platform. With over 140 active and granted patents, this platform can efficiently culture a variety of adherent cell types, including placental cells, mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), CAR-T cells, HEK293 cells for viral vector production, Chinese hamster ovary (CHO) cells, exosomes, and other plant and animal cells. “Operating in perfusion culture, the system also is ideally suited for harvesting extracellular vesicles (EVs) and secretome,” Lewin added. Pluri’s strategic focus has been on developing closed system platforms scalable from bench-top operation to large-scale, automated, commercial GMP production. “We offer proven, reliable processes, with low batch to batch variability, that have been operated in GMP with the approval of major regulatory agencies,” explained Lewin.

Capitalising on opportunities in cell therapy

Lewin sees significant opportunities for CDMOs in advancing complex, cell-based medicines. He highlighted the approval of several strikingly effective cell therapies for previously challenging diseases, such as CAR-T therapies for hematologic cancers (e.g., tisagenlecleucel (Kymriah^®), idecabtagene vicleucel (Abecma®), and lisocabtagene maraleucel (Breyanzi^®) or exagamglogene autotemcel (Casgevy^®) for sickle cell disease and beta thallasemia, to name a few, as a catalyst for the field’s expansion. While current approved products often target diseases with relatively low prevalence and high cost, requiring small-scale manufacturing, Lewin anticipates a shift. “I’m confident that in the coming years we will see products for the treatment of much larger indications and at much lower cost, with consequently very different manufacturing requirements,” he predicted. He highlighted CAR-T therapies as an example, where the development of cell-based allogeneic therapies could address larger patient populations at lower costs. He also foresees an expansion in the range of disease targets for such therapies, from blood cancers to solid tumours, autoimmune conditions and fibrotic diseases.

PluriCDMO is particularly well-positioned to support the development of therapies for larger markets, especially allogeneic products. “Not only do we offer a unique, scalable production system with the capability to produce tens of billions of cells from a relatively small footprint, but we have invested significant resources and expertise in cryopreservation, storage, shipping and recovery of living cells, so that we can support international shipping and distribution of cell-based products and ensure that product quality and efficacy is assured no matter the destination,” Lewin explained.

Navigating the challenges of scale-up

Scaling up from early-stage clinical studies to late-stage development presents a significant hurdle for cell therapies. Lewin emphasised the stark contrast between early-stage and later-stage manufacturing. Early-stage manufacturing typically involves laboratory-scale equipment, significant manual intervention, and the production of a small number of doses for a single clinical site. In contrast, Phase III and commercial-scale manufacturing demand closed, automated processes with minimal manual intervention. “Processes and assays should be operator-independent and validated as such, and if it’s an allogeneic product then the scale of production might need to be very much larger and use appropriately industrial-scale equipment,” he said. Furthermore, the need to ship products globally introduces complexities related to product stability, storage and transport.

Lewin stressed the importance of “beginning with the end in mind.” He argued that addressing scale-up challenges early, even at the early clinical stage, can be beneficial. “Process change is costly, and process change at a late stage in a rush is very costly,” he admitted. For biopharmaceutical companies that have already invested significant resources in late-stage development, PluriCDMO aims to facilitate a smooth transition to commercialisation. “Our goal is to get these companies to the finish line and into commercialisation, hence, we comprehensively plan out how to create the product and what will be required across the supply chain to bring that product to physicians and their patients wherever they might be. Yet, the most critical factor when scaling up is being able to see the big picture and break down the actionable steps needed to continually progress,” Lewin said.

Addressing the challenges of cell-based therapies

CDMOs face several challenges when supporting cell-based therapies, particularly regarding technology and expertise. Lewin acknowledged the diversity of products being developed as a significant, albeit welcome, challenge. “Cell therapy CDMOs need to be able to work with a variety of cell types, potentially a range of gene modifying technologies, autologous as well as allogeneic cell sources, and many other variables,” he explained. PluriCDMO addresses this diversity by focusing on adaptable technology platforms, such as its 3D platform. “Our approach has been to focus on adaptable and robust platforms that can meet the diverse manufacturing challenges that our customers face,” Lewin said.

He also highlighted the challenges faced by regulatory bodies in developing standards for this emerging field. PluriCDMO, as a pioneer in cell therapy development, is committed to working with international agencies and its customers to meet these evolving regulatory standards and ensure patient safety. “We truly see ourselves as a partner, one who brings significant experience and forethought to the clinical research and development process,” Lewin said.

Innovations on the horizon

PluriCDMO is actively working on innovations to further enhance its cell therapy manufacturing capabilities. A key focus is the continued development of its proprietary 3D platform. While initially developed for adherent cell growth, recent research has demonstrated its potential for expanding non-adherent cells, such as primary human T cells. “We are actively researching ways to improve the efficiency of culture for T cell populations with a view to supporting allogeneic CAR-T manufacture,” Lewin explained. PluriCDMO is also collaborating with partners to increase the scale of cell production and expand the range of cell types and products that can be manufactured on the platform. Lewin anticipates the platform’s future use in the manufacture of commercial plant and animal cell-derived products, as well as commercial exosomes and viral vectors. “I fully expect to see our 3D platform involved in the manufacture of commercial plant and animal cell-derived products, and also of commercial exosomes and viral vectors for many applications in the coming years,” he concluded.