A Survey of Population Pharmacokinetic Study on New Drug Applications in Japan

The Ministry of Health Labour and Welfare(MHLW)of Japan issued the"Guidance for Industry : Clinical Pharmacokinetic Studies of Pharmaceuticals" (MHLW‑PK guidance)in 2001 which provided the scope and basic principles of clinical pharmacokinetic(PK)studies that are necessary to submit a new drug application(NDA) . This was the first Japanese guidance to state the utility of the population PK study. The aim of this study was to evaluate the effects of the MHLW‑PK guidance on population PK studies in Japanese NDAs. Three hundred four NDAs(including supplemental NDAs)approved from September 1999 to December 2006 in Japan were surveyed. Information on these NDAs was obtained from data summaries submitted by the NDA applicants which are publicly available on the Pharmaceuticals and Medical Devices Agency website. Population PK analyses were performed in 50 NDAs(16.4%) . Of these NDAs 31 NDAs (10.2%)included Japanese data. The implementation rate of population PK analyses including Japanese data before(1999‑2001)and after the guidance(2002‑2006)increased by more than threefold from 4.1%(5/122)before the guidance to 14.3%(26/182)after the guidance. By therapeutic area the number of population PK analyses was highest for antineoplastic and chemotherapeutic agents. The results of the population PK analyses were reflected in the labeling of 18 NDAs approximately 60% of which were approved in 2006. The MHLW‑PK guidance contributed to the progress of population PK studies in Japan.