In Japan, a research center network consisting of Kyoto University to provide clinical-grade induced Pluripotent Stem Cells (iPSC) and several major research centers to develop iPSC-based regenerative therapies was formed for the clinical application of iPSCs. This network is under the supervision of a newly formed funding agency, the Japan Agency for Medical Research and Development. In parallel, regulatory authorities of Japan, including the Ministry of Health, Labour and Welfare, and Pharmaceuticals and Medical Devices Agency, are trying to accelerate the development process of regenerative medicine products (RMPs) by several initiatives: 1) introduction of a conditional and time-limited approval scheme only applicable to RMPs under the revised Pharmaceuticals and Medical Devices Act, 2) expansion of a consultation program at the early stage of development, 3) establishment of guidelines to support efficient development and review and 4) enhancement of post-market safety measures such as introduction of patient registries and setting user requirements with cooperation from relevant academic societies and experts. Ultimately, the establishment of a global network among iPSC banks that derives clinical-grade iPSCs from human leukocyte antigens homozygous donors has been proposed. In order to share clinical-grade iPSCs globally and to facilitate global development of iPSC-based RMPs, it will be necessary to promote regulatory harmonization and to establish common standards related to iPSCs and differentiated cells based on scientific evidence.
Keywords: AMED, Japan Agency for Medical Research and Development; BLA, Biological License Approval; CFR, Code of Federal Regulations; CiRA, Center for iPS Cell Research and Application; DMF, Drug Master File; ESC, embryonic stem cell; FDA, Food and Drug Administration; FY, fiscal year; GAiT, Global Alliance for iPS Cell Therapies; GCTP, Good Gene, Cell, Cellular and Tissue-based Products Manufacturing Practice; GMP, good manufacturing practice; HLA, human leukocyte antigen; Haplobank; IBRI, Institution of Biomedical Research and Innovation; ICH, The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; IND, Investigational New Drug; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; IRB, Institutional Review Board; J-MACS, Japanese Registry for Mechanically Assisted Circulatory Support; JST, Japan Science and Technology Agency; Japan; LVAD, left ventricular assist device; METI, Ministry of Economy, Trade and Industry; MEXT, Ministry of Education, Culture, Sports, Science and Technology; MHLW, Ministry of Health, Labour and Welfare; NEDO, New Energy and Industrial Technology Development Organization; NIBIO, National Institute of Biomedical Innovation; NIHS, National Institute of Health Science; PAL, Pharmaceutical Affairs Law; PIC/S, The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme; PMD Act, Pharmaceuticals and Medical Devices Act; PMDA, Pharmaceuticals and Medical Devices Agency; Policy; R&D, research and development; RM Act, the Act on the Safety of Regenerative Medicine; RMP, regenerative medicine product; Regenerative medicine; Regulation; Riken CDB, Riken Center for Developmental Biology; U.S., United States; WHO, World Health Organization; iPS cells; iPSC, induced pluripotent stem cell.