Further improvement of the national testing process and international harmonization of regulatory requirements

Although the national test process in Japan has been slightly improved for some products, there are still some parts that are not consistent with the international standards. For example, abnormal toxicity test may be required as a test item which has already been abolished in Europe and the US. In addition, monographs of the Minimum Requirements for Biological Products (MRBP) require Japan-specific general test methods including many animal studies. In the process of pre-approval testing for new vaccine application, enactment of MRBP monographs, preparation of the SLP template and submission of samples for the national test, multiple organizations are involved and the coordination among these multiple organizations is a burden on companies. In addition, the authority which is responsible for national testing is different from that for file reviewing, resulting in duplicated review process. However, the division of roles between the regulatory authority and the testing institution is unclear. Additionally, attendance of prefectural officer at the domestic manufacturing site is necessary during sampling of the test samples, making it substantially impossible to conduct sampling at the overseas manufacturing sites. Therefore, the lead time to supply imported vaccines cannot be shortened. Furthermore, when national testing performed by using only SLP, sampling of test samples is performed in accordance with the regulations. This is a waste of resources and products. Listing in MRBP is immediately required when a new vaccine is approved in Japan. If similar products are listed in MRBP, the new product will need to be in compliance with the respective monograph despite differences in product characteristics. It is practically impossible to introduce vaccines that has been widely used for a long time in Europe, etc. as the information on raw materials included in the master cell bank and/or master seed may not meet the criteria required by standard for biological ingredient (SBI).


  • Optimize collaboration of PMDA and MHLW which are responsible for file review, and National Institute of Infectious Diseases (NIID) and prefectural offices which are responsible for national testing
  • Revision of the sampling method for national testing which enables companies to conduct sampling process at overseas manufacturing sites.
  • Rationalization of national testing processes including reviewing documents only or reducing the number of test lots by utilizing SLP
  • Discontinuation of immediate listing of new vaccines on MRBP.
  • Harmonization of Japanese requirements with international standards, including discontinuation of abnormal toxicity testing, replacement of in vivo testing with in vitro testing, and interchangeability of WHO and European pharmacopoeia general testing methods.
  • Reconsideration of SBI application for bio-derived materials contained in the master cell bank and/or master seed in the vaccine products approved in EU countries.