Objective: Among all the new drugs approved in Japan, the regulatory review time for some greatly exceeds the median each year. However, to our knowledge, no reports have detailed why the review times were prolonged in these instances. In this study, we examined new applications (NDAs) whose review times were more than twice as long as the median each year in order to pinpoint the cause of delayed approval. Methods:We analyzed 564 NDAs that were approved in Japan between 2005 and 2011.Results: Thirty-eight NDAs were found to have prolonged review times. Of the 38 NDAs, the most popular therapeutic categories were oncology drugs and vaccines, and 28 of the drugs had already been approved in foreign countries when approval was granted in Japan, some with lag times of more than 36 months. This observation suggests that prolonged regulatory review time further worsens lags in drug approval. "Problem related to clinical data" was cited as the most common reason for prolonged review time. For most of the NDAs categorized into this group, additional clinical trials were conducted during the same review time without NDA withdrawal because the clinical study design was inappropriate, a deficiency in the evidence of a dosage regimen was observed, or efficacy was not confirmed in a confirmatory study trial. Conclusion:Our analyses of these trial details indicate the importance of determining the optimal dosage regimen carefully and utilizing objective endpoints in clinical trials.Keywords: Regulatory review; Drug development; Clinical trial; Drug lag; New drug applications; Regulatory review times; Access gap ObjectiveIn Japan, approval of a new drug abroad that is not approved for use in Japan has become a major issue [1][2][3][4][5][6][7][8]. This problem has been termed drug lag, and its direct cause includes delays in the start of clinical development, the progress of clinical trials, and in the regulatory review. In order to minimize these delays, the Japanese regulatory authorities, the Ministry of Health, Labour and Welfare (MHLW), and the Pharmaceuticals and Medical Devices Agency (PMDA), have conducted several projects [9]. As a result, the PMDA has shortened the average review time to