A descriptive research: Exclusion from submitted clinical data package in the review process of new drug approval due to GCP violation in Japan

Introduction: In Japan, the PMDA conducted inspections based on GCP in the review process of the submission of NDAs or sNDAs. In this descriptive study, we examined in detail the contents of exclusion data from submitted clinical data package subjects in the results of GCP inspections in Japan for NDAs or sNDAs. Methods: For NDAs or sNDAs approved in Japan between January 2007 and December 2017, we gathered information about the PMDA's conclusion from review reports, concerning the results of the GCP on-site inspection. Results: For 1193 NDAs and sNDAs approved in Japan between 2007 and 2017, there were 37 cases in 33 applications of non-compliance with GCP, including 1 by the sponsor and 32 at the clinical trial site. Of the 32 applications at the clinical trial site, 9 cases were categorized as "General findings" and 28 as "Findings for individual subjects." Of the 9 "General findings" cases, problems related to the IRB were most common (44.4%), while faulty record keeping was the most common (60.7%, 95% confidence interval 42.6%-78.9%) problem in the 27 "Findings for individual subjects" cases. Violations of GCP were mostly found in 2007 and 2009, but few were found after 2013. Conclusion: In this study, we revealed that record keeping was the most common reason for exclusion from the analysis data of subjects in the results of GCP inspections. It is necessary to be careful in maintaining medical records, especially when conducting clinical trials without using electronic medical records.