The ex-vivo Cell and Gene Therapy medicine field has entered into a new era driven by the registration of the first autologous products namely Kymriah (Novartis, 2017, US), Yescarta (Kite/Gilead, 2017, US) and Strimvelis (GSK/Orchard, 2016, Europe). Despite this very promising context, cell-based processes are far from being mature from an industrial perspective. One proof is the frequent news of quality issues (Out-of-Specification) on cell therapy products. The industry overall has a driving need to develop “next-generation” autologous processes with the objective of improving manufacturability (process length, automation et. al.) and to become increasingly commercially competitive.
Following closely behind the recent success of autologous cellular therapies, allogeneic T-cell therapies are moving toward late-stage clinical trials and commercial registration with the promise of having these breakthrough therapies available for market launch. Consequently, a new race to market has begun among “allogeneic CAR-T pioneers” (e.g. Servier, Cellectis, Allogene, Crispr Therapeutics, Precision Bioscience et. al.).
Cell and Gene Therapy companies need to invest time, effort and funds to improve process manufacturability as it will be the key for long-term commercial success.
T-Cell-based products can be classified as non-traditional therapeutic products in the biotechnology industry and rely on complex and challenging process optimization and manufacturing. The most common traits of both allogeneic and autologous processes are:
High variability due to the nature of the starting material (e.g. variety of cell types, living biological organisms). Non-industrial equipment that is often only partially compatible with current GMP standards
Process scale with process volume ranging from a few millimeters to a few liters
Aseptic processing with no possibility to perform sterile filtration
Economy of scale that is especially challenging for autologous production processes
Contract development and manufacturing organizations need to play a critical role in the scale-up and industrialization of cellular therapies by providing customized tools and processes. The Manufacturing by Design approach for addressing the industrialization of cell therapies allows for optimal production conditions.