Computational fluid dynamics modeling, a novel, and effective approach for developing scalable cell therapy manufacturing processes.

Abstract

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor‐intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high‐quality iPSC derivatives under controlled conditions. The current scale‐up methods used in cell therapy processes are based on empirical, geometry‐dependent methods that do not accurately represent the hydrodynamics of 3D bioreactors. These methods require multiple iterations of scale‐up studies, resulting in increased development cost and time. Here we show a novel approach using computational fluid dynamics modeling to effectively scale‐up cell therapy manufacturing processes in 3D bioreactors. Using a GMP‐compatible iPSC line, we translated and scaled‐up a small‐scale cardiomyocyte differentiation process to a 3‐L computer‐controlled bioreactor in an efficient manner, showing comparability in both systems.