Human induced pluripotent stem cells (hiPSCs) are manufactured as advanced therapy medicinal products for tissue replacement applications. With this aim, the feasibility of hiPSC large-scale expansion in existing bioreactor systems under current good manufacturing practices (cGMP) has been tested. Yet, these attempts have lacked a paradigm shift in culture settings and technologies tailored to hiPSCs, which jeopardizes their clinical translation. The best approach for industrial scale-up of high-quality hiPSCs is to design their manufacturing process by following quality-by-design (QbD) principles: a scientific, risk-based framework for process design based on relating product and process attributes to product quality. In this review, we analyzed the hiPSC expansion manufacturing process implementing the QbD approach in the use of bioreactors, stressing the decisive role played by the cell quantity, quality and costs, drawing key QbD concepts directly from the guidelines of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

人类诱导多能干细胞 (hiPSC) 被制造为用于组织替代应用的先进治疗药物产品。为此，已经测试了在当前良好生产规范 (cGMP) 下在现有生物反应器系统中大规模扩展 hiPSC 的可行性。然而，这些尝试缺乏针对 hiPSCs 的文化设置和技术的范式转变，这危及了它们的临床转化。高质量 hiPSC 工业放大的最佳方法是按照质量源于设计 (QbD) 原则设计其制造过程：基于产品和过程属性与产品相关的科学、基于风险的过程设计框架质量。在这篇综述中，我们分析了在使用生物反应器时实施 QbD 方法的 hiPSC 扩展制造过程，