Human pluripotent stem cell‐derived products: Advances towards robust, scalable and cost‐effective manufacturing strategies

Abstract

The ability to develop cost-effective, scalable and robust bioprocesses for human pluripotent stem cells (hPSCs) will be key to their commercial success as cell therapies and tools for use in drug screening and disease modelling studies. This review outlines key process economic drivers for hPSCs and progress made on improving the economic and operational feasibility of hPSC bioprocesses. Factors influencing key cost metrics, namely capital investment and cost of goods, for hPSCs are discussed. Step efficiencies particularly for differentiation, media requirements and technology choice are amongst the key process economic drivers identified for hPSCs. Progress made to address these cost drivers in hPSC bioprocessing strategies is discussed. These include improving expansion and differentiation yields in planar and bioreactor technologies, the development of xeno-free media and microcarrier coatings, identification of optimal bioprocess operating conditions to control cell fate and the development of directed differentiation protocols that reduce reliance on expensive morphogens such as growth factors and small molecules. These approaches offer methods to further optimise hPSC bioprocessing in terms of its commercial feasibility.

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

“…Current technologies for pluripotent stem cell expansion hardly fulfil the demands of regulatory boards (Kurtz et al, 2014) and the needs of clinical use (Kamao et al, 2014), as they are associated with low cost-efficiency (Jenkins & Farid, 2015), lack stringent quality control, or do not meet good manufacturing practices (GMP) standards (Elseberg, Salzig, & Czermak, 2015). Therefore, the development of a standardized, scalable method for pluripotent stem cell expansion that is cost-effective and compatible with automation is of great interest.…”

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals

“…The need for evaluating chronic exposure (i.e., >3 weeks) to drugs will involve further optimization to ensure viability and sustainable functionality of cells in long‐term culture. For high‐throughput drug‐testing efforts, scalability of hPSC‐derived cells may require improved conditions, such as supportive extracellular matrices or automation in bioreactors [], for robustness of production.…”

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

“…For example, the economics of allogeneic expansion for pluripotent stem cells (iPSCs and ESCs) have been recently modeled and described both for the upstream [58] as well as for the subsequent downstream operations [59]. This is not yet clearly addressed in the case of autologous large-scale expansion, where most likely a generic solution does not exist and optimal solutions will be case specific, based on inherent cell or donor properties as well as practical limitations (e.g.…”