cGMP-compliant large-scale manufacturing of human-induced pluripotent stem cells: current progress and challenges

Induced pluripotent stem cells (iPSCs), which can be applied to disease modeling, regenerative medicine, and cultivated meat, among other uses, have opened a new era in the biomedical field. To obtain sufficient high-quality cells for these applications, a current good manufacturing practice (cGMP)-compliant large-scale expansion is necessary. It indicates that the entire process for producing iPSCs should adhere to cGMP regulations, encompassing both upstream steps, such as raw material collection, reprogramming, and large-scale expansion, as well as downstream steps, including harvesting, concentrating, and cryopreserving the cells. Importantly, well-established critical quality attributes are mandatory to ensure the quality of the produced cells. For decades, huge efforts have been made to initiate and develop each step of the process. However, there are still limitations and obstacles that slow down the progress of the cGMP large-scale production of iPSC. Therefore, in this review, we summarize the accomplishments and challenges of current technologies involved in making applicable and clinical iPSCs. Throughout this, future directions and solutions can be suggested for the production of large-scale, high-quality iPSCs.