Abstract
Objective: Advances in comparability (biosimilarity) evaluation techniques and trends in regulations and approvals in Japan and abroad were examined.
Methods: The data was collected from the National Institute of Health Sciences (NIHS) Annual Report, the Pharmaceuticals and Medical Devices Agency (PMDA), and the NIHS Division of Biological Chemistry and Biologicals website. Advances in biosimilar evaluation techniques and trends in regulations and approvals in Japan and abroad were examined.
Results and Discussion: The European Medicines Agency(EMA) has continuously published quality guidelines (GLs), non-clinical and clinical study GLs, and product group-specific non-clinical and clinical GLs since 2005. In Japan, the guidelines to ensure the quality, safety and efficacy of biosimilar products (Pharmaceutical and Food Safety Bureau Notification, No. 0304007) was issued by the Ministry of Health, Labour and Welfare (MHLW). In the U.S., a law was passed in 2010 setting forth regulatory requirements for biosimilars, and in 2012, the FDA released a draft guidance. Comparability studies including bioassays are needed to demonstrate that a biosimilar product has no meaningful differences when compared with the reference product. In the comparability, N-linked glycan profiles, the antibody-dependent cellular cytotoxicity (ADCC) activity of antibody drugs, and FcγRⅢ, a binding activity, are often important. The NIHS is also conducting research on related evaluation methods. Among the most important biological characteristics of monoclonal antibodies (mAbs), it is necessary to compare the Fc-mediated functions that induce immune-cell activation. The evaluation methods for biosimilars have been being developed since 2013. A generic bioanalytical method was developed to quantify therapeutic IgG1 mAbs in mouse sera by combining an easy, sample preparation method with LC/MS using selected reaction monitoring. In Japan, 32 products including cytokines, erythropoietins, antibodies, etc. were approved and have been used to date.
