A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of allogeneic human induced pluripotent stem(-Like) 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 induced pluripotent stem cells (iPS cells) or iPS cell-like 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. 0907-5, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Allogeneic Human Induced Pluripotent Stem(-Like) Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from allogeneic human iPS cells (or iPS cell-like cells), in addition to similar points to consider that are described previously for allogeneic human stem cell-based products. Major additional points include 1) possible existence of allogeneic human iPS cell-like cells that are different from iPS cells in specific biological features; 2) the use of allogeneic human iPS(-like) cells as appropriate starting materials for regenerative medicine, where necessary and significant; 3) establishment of an allogeneic human iPS(-like) cell line and its characterization; 4) establishment of well-characterized stable cell banks and relevant intermediate cell products, if necessary; 5) concerns about the presence of undifferentiated cells in final products; such cells may cause ectopic tissue formation and/or tumorigenesis; and 6) concerns about undesirable immunological reactions that may be caused by the final products. 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.