2020 Volume 55 Issue 2 Pages 169-178
Objective: To study the history of the Division of Biological Chemistry and Biologicals, National Institute of Health Sciences (NIHS) focusing on the 30-year history of developing quality evaluation methods for biopharmaceuticals and their international harmonization. Methods: Information on Division of Biological Chemistry and Biologicals reported in the Bulletin of the NIHS each year was analyzed. Approval information was obtained from the website of the Division of Biological Chemistry and Biologicals. The guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) were obtained from the website of the Pharmaceuticals and Medical Devices Agency (PMDA). Results and Discussion: Stage 1 (1989-1998) Twenty biopharmaceuticals were approved. The development of quality evaluation methods was as follows, e.g. the replacement of a recombinant human growth hormone and human insulin in vivo assay with a high-performance liquid chromatography (HPLC) assay. Structural analysis of the oligosaccharide chain of r-hEPO, especially using fluorophore-assisted carbohydrate electrophoresis (FACE) was performed. The ICH guidelines for the quality of biotechnological/biological products, Q5B and Q5C, were implemented. Joined the Inter-pharmacopoeial (EP, JP and USP) open conference on harmonization of biotechnology-derived product standards in 1993. Stage 2 (1999-2008) Thirtyfive biopharmaceuticals were approved. The development of quality evaluation methods such as mass spectrometric glycoform profiling of r-hEPO using LC/ESI-MS were performed. The ICH guidelines for quality, Q5A(R1), Q5D, Q6B and Q5E, were implemented. Stage 3 (2009-2018) Eighty-two biopharmaceuticals were approved. The development of quality evaluation methods, such as rapid evaluation for heterogeneities in monoclonal antibodies using LC/MS with a column-switching system. Harmonization with the ICH guidelines for Pharmaceutical Product Lifecycle Management (Q12) was implemented. Recent topics of research in the characterization and quality control of biopharmaceuticals in Japan, such as monoclonal antibodies, are also discussed.
