Comparison of Population Pharmacokinetics-Related Information in Drug Labeling Between Japan, the United States, and the European Union.

Quantitative decision making using the population pharmacokinetic (PPK) approach is useful not only in drug development but also in clinical practice. A previous study investigating the labeling of new active substances (NASs) approved between 2012 and 2015 in Japan and the United Sates reported a significant gap in the percentage of drug labeling providing PPK-related information between Japan (17.6%) and the United States (56.6%). However, whether the state of Japanese labeling has improved compared with the US and European Union (EU) labeling after a Japanese guideline on PPK analysis was released in 2019 has not been investigated yet. This study evaluated the labeling of 138 NASs approved in Japan, the United States, and the EU in or after 2019 and found that the percentage of NASs which provide PPK-related information in the drug labeling with an explicit statement that it was based on PPK analysis was 50.0%, 46.2%, and 76.9% in Japan, the United States, and the EU, respectively, indicating a remarkable improvement in Japan labeling. However, we also found that Japan labeling was still considerably behind the US/EU labeling in terms of application of quantitative decision making by the PPK approach. This is because the percentage of NASs with PPK-derived information used to support dosing recommendations in special populations was much lower in Japan labeling than in the US/EU labeling. While the PPK guideline played an important role in improving Japan's drug labeling, more utilization of PPK-derived information in quantitative decision making is required for healthcare professionals and patients in Japan.