2019 Volume 9 Issue 2 Pages 95-102
The Project for the Promotion of Progressive Medicine, Medical Devices, and Regenerative Medicine by the Ministry of Health, Labour and Welfare was established in 2012. One of the projects that was adopted, “evaluation procedures for the efficacy and safety of pharmaceuticals that use pharmacogenomics,” conducted a non-clinical study and early-phase clinical trials on investigational drugs, and evaluated the effects of genetic polymorphisms of drug-metabolizing enzymes and transporters primarily involved in those trials. This work was conducted at the Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Tohoku University, in cooperation with the National Institute of Health Sciences and Pharmaceuticals and Medical Devices Agency. As a main achievement of this project, we compiled the current scientific information on genetic polymorphisms, which would be evaluated during these non-clinical studies and phase I clinical drug trials in Japanese subjects/patients, obtained through this project and scientific papers. This points to consider document focuses on the genetic polymorphisms of drug metabolizing enzymes (cytochrome P450 enzymes among others) and transporters with reported functional significance and allele frequencies of 1% or higher in the Japanese population, and outlines in vitro procedures for the evaluation of their functional effects on investigational drugs. This document also provides examples of genetic polymorphisms and somatic mutations of proteins involving drug efficacy or adverse drug reactions. We believe that this information will be helpful to accelerate future research and continued discussions on drug development using pharmacogenomic information (e. g., dose adjustment and avoidance of adverse reactions) in Japan and possibly other East Asian countries. In addition to introduce this document, related guidelines/guidances of ICH, EMA and FDA were outlined.
