Alexandra Haase, Arjang Ruhparwar, Ulrich Martin
The development of induced pluripotent stem cells (iPSCs) has transformed the field of regenerative medicine. However, to use iPSCs for therapeutic applications, iPSC-based products must be produced under Good Manufacturing Practice (GMP) conditions. This process involves reprogramming somatic cells, characterizing and banking iPSC lines, introducing therapeutic transgenes if necessary, and scaling up cell expansion and differentiation for clinical use. This review provides an overview of the relevant regulatory authorities and relevant regulations in the US, Europe, and Japan. It also discusses the current challenges and opportunities in producing GMP-compliant iPSCs. These challenges include the need for defined culture media, as well as developing all the required GMP-compliant processes, such as reprogramming, establishing iPSC clones, and manufacturing processes that lead to the final advanced therapy medicinal product (ATMP). For autologous products in particular, this can be complicated by cell line-specific variation of proliferation velocity and differentiation biases. The review also discusses attempts to develop automated closed systems. It emphasizes the importance of ensuring the sterility, identity, (epi)genetic integrity, and functionality of the final cell products to guarantee the safety and the efficacy of iPSC-based therapies. However, the need for reproducibility, rigorous quality control and safety requirements has resulted in high regulatory hurdles and extremely high costs, which often prevent the initiation of clinical trials. Overcoming these challenges will enable iPSCs to play an integral role in future medicine and offer new treatment options for various diseases.