Large-scale expansion of pluripotent stem cells (PSC) in a robust, well-defined, and monitored process is essential for production of cell-based therapeutic products. The transition from laboratory-scale protocols to industrial-scale production is one of the first milestones to be achieved in order to use both human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) as the starting material for cellular products. The methods to be developed require adjustment of the culture platforms, optimization of culture parameters, and adaptation of downstream procedures. Optimization of expansion protocols and their scalability has become much easier with the design of bioreactor systems that enable continuous monitoring of culture parameters, continuous media change, and support software for automated control. This chapter highlights the common properties that are required for production of scalable, reproducible, homogeneous, and clinically suitable cell therapy products. We describe the available platforms for large-scale expansion of PSCs and parameters that should be considered when optimizing the expansion protocols in a scalable bioreactor. All the above are detailed in the light of the requirements and challenges of bringing a cell-based therapeutic product to the clinic and ultimately to the market. We discuss some considerations that should be taken into account, such as cost-effectiveness, good manufacturing practice, and regulatory guidelines. Graphical Abstract.
Keywords: Bioreactor; Cell therapy; Embryonic stem cells; Large scale; Pluripotent stem cells; Process development; Production.