Clinical Development and Approval Review of New Drugs in Japan
Taro Ishibashi (Senior Researcher, Pharmaceutical and Industrial Policy Research Institute)
Shunsuke Ono (Associate Professor, Department of Drug Evaluation Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo)
(No. 47: Published in October 2009)
The study examined the clinical development period (from the date of initial clinical trial plan submission to the date of application for approval), the review period (from the date of application for approval to the date of approval), and the combined development period (from the date of initial clinical trial plan submission to the date of approval) for new drugs approved in Japan from 2000 to 2008, and the factors related to the length of these periods.
The median clinical development period from 2000 to 2008 was 59.5 months (5.0 years) and 44.6 months (3.7 years) in 2008, reflecting the diversification of development strategies and their fluctuations and variations. The use of foreign clinical data as the basis for domestic applications for approval was increasing, contributing to the shortening of the period. The median review period over the nine-year period was 20.6 months (1.7 years), and 19.0 months (1.6 years) in 2008. Although the review period tended to shorten after the establishment of PMDA in April 2004, the process from the submission of responses to inquiries after the initial interview to expert consultation through additional inquiries, which accounts for approximately two-thirds of the review period, However, the process from the submission of responses to inquiries after the initial interview through additional inquiries to the expert consultation, which accounts for approximately two-thirds of the review period, did not show any reduction over time.
Regression analysis of the relationship between clinical development period, review period, and length of development period and factors related to approved items, applicant companies, clinical development, and approval review showed that the clinical development period was significantly shorter for items for which domestic clinical trials were conducted except for NMEs, items with approval conditions, and items with foreign clinical data as evaluation data. As for the review period, applications submitted after the establishment of PMDA and priority review items were significantly shorter. In addition, the review period was significantly shorter for items for which pre-application consultation was conducted, while the clinical development period was longer.
Although the applicant's evaluation of the PMDA has been improving, in order to achieve the FY2011 target set in response to the "Five-Year Strategy for the Creation of Innovative Drugs and Medical Devices," further reduction of the time required by both the administration and the applicant is necessary, including increasing the number of PMDA staff, introducing a pre-evaluation consultation system, and strengthening progress management of reviews. In addition, it is necessary to consider measures such as clarifying the standard review timeline, streamlining the inquiry process, and reviewing the Pharmaceutical Affairs and Food Sanitation Council.
Changes in clinical development time (initial clinical trial plan notification (CTPN) to NDA), review time (NDA to approval), and development time ( Changes in clinical development time (initial clinical trial plan notification (CTPN) to NDA), review time (NDA to approval), and development time ( initial CTPN to approval) of new drugs approved in Japan during 2000 - 2008 were evaluated.
Clinical development times were fluctuating, with a median of 59.5 months (5.0 years) during 2000 - 2008 and 44.6 months (3.7 years) in 2008. Use of foreign clinical data in Japanese NDAs was increasing and contributing to abridge clinical development times. Review times were on a decline since the establishment of PMDA in April 2004, with a median of 20.6 months (1.7 years) and 44.6 months (3.7 years) in 2008. No improvement, however, was observed in the time spent from the No improvement, however, was observed in the time spent from the submission of responses to the first set of queries after the Interview Meeting and subsequent queries to the Expert Meeting, which accounted for two- thirds of the review time. No improvement, however, was observed in the time spent from submission of responses to the first set of queries after the Interview Meeting and subsequent queries to the Expert Meeting, which accounted for two- to three-of-the review time.
Multiple regression analyses to estimate factors associated with the length of the three time periods suggested that clinical development times were Results also indicated that review times were significantly shorter in NDAs submitted to the Expert Meeting, which accounted for two thirds of the review time. Results also indicated that review times were significantly shorter in NDAs submitted to PMDA after April 2004 and drugs designated as priority reviews. Results also indicated that review times were significantly shorter in NDAs submitted to PMDA after April 2004 and drugs designated as priority reviews.
Nevertheless, measures such as standardized review timelines with Nevertheless, measures such as standardized review timelines with clear milestones, efficient query-and-response procedures, and re-examination of the role of the Pharmaceutical Affairs and Food Sanitation Council Nevertheless, measures such as standardized review timelines with clear milestones, efficient query-and-response procedures, and re-examination of the role of the Pharmaceutical Affairs and Food Sanitation Council should be considered, in addition to the ongoing increase in PMDA staff, implication of pre-NDA evaluation consultations, and strict time management, to further shorten the process time of the process. The PMDA will continue to work to further shorten the process time of both the regulatory agencies and applicants and achieve the target review time set for fiscal year 2011 in light of the 5-Year Strategy for the The PMDA is currently working on a 5-Year Strategy for the Creation of Innovative Pharmaceuticals and Medical Devices.