Meeting Report: PMDA Public Workshop on Pharmacometrics at Japan
Shinichi Kijima, Yoshinori Ochiai, Akihiro Ishiguro · CPT Pharmacometrics & Systems Pharmacology · 2020
In recent drug development, applications of pharmacometrics and modeling and simulation (M&S) have become of increasing importance.A research group that consists of experts in academia, industry, and regulatory agency has been developing practical guidelines for pharmacometrics and M&S based on latest scientific findings.This paper outlines a public workshop to exchange opinions widely among stakeholders of draft guidelines on exposure-response analysis and physiologically-based pharmacokinetic model's analysis, which was held in Japan in July 2019.Recent drug developments have paid attention to quantitative modeling and simulation (M&S) as a tool to examine study designs or optimize the dosing regimen of a drug.In Japan, the increasing number of drug approval applications have recently used results with M&S approach as rationales for establishing the optimized dosing regimen and precautions in the new drug application (NDA) documents.According to a survey on M&S utilization in NDAs of 38 drugs with a new molecular entities submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) in fiscal year (FY) 2018, a population pharmacokinetic (PPK) analysis was studied in ~ 70% of NDAs, and a PPK/pharmacodynamic (PD) analysis or exposure-response (ER) analysis were studied in ~ 60% of NDAs (Figure 1).These data also indicate that assessments using empirical models, including PPK analysis, were increased yearly in Japan.In the 150 NDAs submitted between FY2014 and FY2016, 1 a physiologically-based pharmacokinetic (PBPK) model analysis was studied mainly to examine drug interactions in ~ 10% of NDAs.A notification "Clinical pharmacokinetics of drugs" 2 issued by the Ministry of Health, Labour, and Welfare (MHLW) in 2001 had showed basic concepts of application of PPK analysis to evaluate on clinical PKs.With respect to ER analysis and PBPK model analysis, no relevant guidelines have been issued in Japan.Such unavailability of the guidelines and the current situation of M&S utilization in drug developments in Japan have led to increased needs to develop new guidelines for M&S to facilitate appropriate application of M&S for regulatory purpose.The Japan Agency for Medical Research and Development (AMED) funded research group consisting of experts from academia, industry, and regulatory authority started activities in 2014 to develop guidelines for M&S.The AMED research group has engaged in preparing three guidelines for PPK and PPK/PD analyses, and ER