Process parameter development for the scaled generation of stem cell‐derived pancreatic endocrine cells

Abstract Diabetes is a debilitating disease characterized by high blood glucose levels. The global prevalence of this disease has been projected to reach 700 million adults by the year 2045. Type 1 diabetes represents about 10% of the reported cases of diabetes. Although islet transplantation can be a highly effective method to treat type 1 diabetes, its widespread application is limited by the paucity of cadaveric donor islets. The use of pluripotent stem cells as an unlimited cell source to generate insulin‐producing cells for implant is a promising alternative for treating diabetes. However, to be clinically relevant, it is necessary to manufacture these stem cell‐derived cells at sufficient scales. Significant advances have been made in differentiation protocols used to generate stem cell‐derived cells capable of reversing diabetes in animal models and for testing in clinical trials. We discuss the potential of both stem cell‐derived pancreatic progenitors and more matured insulin‐producing cells to treat diabetes. We discuss the need for rigorous bioprocess parameter optimization and identify some critical process parameters and strategies that may influence the critical quality attributes of the cells with the goal of facilitating scalable manufacturing of human pluripotent stem cell‐derived pancreatic endocrine cells