Facts and Issues of Submitting Applications (Public Knowledge-Based Applications) for Unapproved and Off-label Drugs With High Medical Needs in Japan.

Background: In Japan, to promote the development and application of unapproved and off-label drugs, a review pathway known as the "public knowledge-based application" was established in 1999. This pathway allows companies to submit applications without clinical trials if the drug has publicly known efficacy and safety and is deemed highly necessary for medical purposes. Objective: The aim of this study is to analyze information published on government websites and to clarify what the criteria for "public knowledge" or "medically necessary" that apply to "public knowledge-based application" that are not yet clear. Methods: We analyzed the correlation between the evidence presented in applications and the progression from the determination of high medical needs to regulatory approval for unapproved and off-label drugs requested for development by patient groups and academic societies in Japan between August 2013 and March 2022. Results: Of the 171 requests, 54 were judged to meet the criteria for medical necessity, and 25 of these were judged to meet the criteria for public knowledge-based application. Of the requests that did not meet the criteria for medical necessity, 90% involved existing domestic therapies. Seventy-two percent of requests meeting the public knowledge-based application criteria involved drugs with standard use in 6 Western countries. Conclusion: This study suggests that the availability of existing domestic therapies and the approval or standard use status of a drug in the 6 Western countries influence the judgment of the applicability of public knowledge-based applications.