Impact of “Guidance for Industry: Clinical Pharmacokinetic Studies of Pharmaceuticals” on New Drug Approvals of Central Nervous System Drugs in Japan

「Background」 A pharmacokinetic (PK) study, which is classified as one of the human pharmacology studies defined by the ICH-E8 guideline,1) has become a critical component of a complete clinical data package for new drug application (NDA).2) While the three preliminary studies, single-dose, multipledose and, food-effect studies have been conducted in healthy subjects, pharmacokinetics had been rarely evaluated in exploratory or confirmatory trials in patients.3) Thus, information on the relationship between PK and efficacy or safety has been historically insufficient in NDAs in Japan. In 2001, the Ministry of Health, Labour and Welfare (MHLW) of Japan introduced the “Guidance for Industry: Clinical PK Studies of Pharmaceuticals” (MHLW-PK guidance) as the first guidance for clinical PK studies in Japan.4) The guidance describes the scope and basic principles of clinical PK studies that are necessary to submit NDA in Japan. In this commentary, formal and reference data of central nervous system (CNS) drugs for NDAs in Japan are surveyed to evaluate the impact of MHLW-PK guidance.