Utilization of New Approach Methodologies (NAMs) in regulatory submissions for medicated cosmetics in Japan.

New Approach Methodologies (NAMs), such as in vitro assays, in silico models, and integrated approaches to testing and assessment, have gained increasing attention as alternatives to traditional animal testing in regulatory toxicology. This review provides a comprehensive overview of the current challenges and prospects of utilizing NAMs in regulatory submissions for medicated cosmetics in Japan. We analyzed safety data packages for medicated cosmetics approved in Japan between fiscal years 2020 and 2024. NAMs were used in 22 of 115 tests and in 10 of 25 products. The frequency of use of NAMs was high for tests in which methods were clarified in Japanese regulations, such as those for acute ocular mucosa irritation tests. Based on these results, we concluded that the issuance of regulations and collaboration among stakeholders are important factors in promoting the use of NAMs. Drawing on regulatory guidance, submission practices, and international harmonization trends, we discuss the incorporation of NAMs in safety assessments, the remaining gaps in regulatory acceptance, and practical considerations for applicants. This review will support regulators, industry and academic scientists, and other stakeholders in advancing scientifically robust and ethically responsible safety evaluation frameworks.