New drug approval times and clinical evidence in Japan

Background: Although overall Japanese approval times declined after the establishment of a new review agency, they still vary significantly from one new drug application (NDA) to another. The causes of these variations have not been investigated quantitatively. Objective: To investigate associations between the approval times and properties of the NDAs such as the results and quality of clinical trials and to examine the Japanese NDA review system. Methods: For the NDAs approved between 1996 and 2003, the characteristics of NDAs including application and approval dates, review status, applicant characteristics, and clinical results were obtained from a survey and other public sources. Regulatory characteristics at different times including the number of NDAs in backlog were also estimated from several sources. Results: Approval times varied significantly across therapeutic categories, review teams, and before and after the new review agency. Use of consultation services and prior number of NDA submissions were negatively associated with the length of approval times. Merger and acquisition experience of the applicants, the amount of clinical data, and the number of NDAs in backlog in the review teams were associated with longer approval times. The way of efficacy establishment was not associated with the length of approval times, but safety profiles of products were associated with the time. Use of foreign clinical data was generally not associated with the length of approval times. Conclusions: Several characteristics of applicants, burdens on the reviewers, clinical data package, and regulatory mandates such as predefined time-line goals were associated with the outcome of the review process in Japan. (c) 2005 Elsevier Inc. All rights reserved.