A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of allogeneic human somatic stem cells.

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from allogeneic human somatic stem cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-3, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Allogeneic Human Somatic Stem Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper describes the background information and development of our study and the resulting guidance. For products derived from allogeneic somatic stem cells, major points to consider include 1) history, the source, and derivation of starting cells; 2) donor screening/testing and donor eligibility, especially in relation to the presence of adventitious agents, potential occurrence of donor-derived diseases, and immunocompatibility; 3) clinical records of a donor; 4) multipotency and self-replication ability of allogeneic human somatic stem cells; 5) cell banking; 6) potential presence of viruses in the final product; 7) extensive characterization of the cells at critical stage(s) of manufacture; 8) robustness of the manufacturing process; 9) quality consistency of the products such as the final products and critical intermediate(s) if any; and 10) robust application and function of the final products in a cell environment different from where the original cells were localized and were performing their natural endogenous function. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities.