Global Regulatory Pulse

PMDA Submission Strategy and CRO Limitations, Part 1

In Asian Market, Consulting, Regulatory by Akira Toyama

Although Ministry of Health, Labour, and Welfare (MHLW) ultimately approves medical devices in Japan, Pharmaceuticals and Medical Devices Agency (PMDA) handles all approval processes. PMDA is a Japanese governmental organization, similar in function to the Food and Drug Administration (FDA) in the United States or the European Medicines Agency in Europe.

PMDA handles the following tasks:

  • Drug and medical device testing based on scientific review of market authorization applications based on Japanese pharmaceutical law.
  • Advice in clinical trials or in the preparation of dossiers for the registration procedure NDA.
  • Inspection and conformity assessment of Good Clinical Practice (GCP), Good Laboratory Practice (GLP), and Good Post-Marketing Study Practice (GPSP).
  • Auditing of manufacturers to ensure they conform to Good Manufacturing Practice (GMP) and have a suitable Quality Management System (QMS).
  • Post-marketing drug safety: The collection, analysis, and distribution of data on the quality, efficacy, and safety data of medicines and medical devices.
  • Victim compensation: Payment of medical costs, lost wages, and pain and suffering for those who suffer injury or disability resulting from the use of medical products.

PMDA has a lot of procedures foreign manufacturers of medical devices are not familiar with. In order for any medical device companies to successfully obtain approval of their products, it is essential that they closely work with an organization such as contract research organizations (CROs) which are familiar with and knowledgeable about Japanese law, custom, market, and medical device industry/market. In a similar manner to dealing successfully with FDA, dealing with PMDA requires experience and specialized knowledge on procedures as well as understanding of Japanese culture. You can obtain this expertise from Japanese CROs, but because of the clinical and scientific nature of the transaction which occurs, solid preclinical, clinical, and scientific knowledge and expertise of the chosen organization are essential. In addition, because all communication occurs in Japanese, ability of the CRO to conduct work in English efficiently is very important. For instance, this becomes a critical issue especially when safety reporting of adverse events needs to be conducted. In addition, acquisition and verification of clinical test data and medical records of subjects is not straightforward because many Japanese clinical research associates (CRAs) are not bilingual, and some software utilized for clinical data acquisition and processing can only handle Japanese. In addition, many smaller medical institutions have not started using Electronic Data Capture (EDC), and manual processing of clinical data is required. If a sponsor would like to choose only sites which have the capability to use EDC, this often results in participation of large medical centers only. Furthermore, Key Opinion Leader (KOL) networks are very complex and delicate. If two KOLs do not get along with each other, sometimes these KOLs cannot be in a single clinical trial simultaneously. Therefore, ordinary tasks such as clinical monitoring can be a source of potentially serious problems for sponsors overseas. Relatively few Japanese CROs have medical device clinical trial experience; therefore, their KOL network with proper clinical experience is limited. This puts additional pressure to securing enough CRAs with enough medical device clinical trial experience. Based on these issues, it is very important to choose a CRO which can execute a medical device clinical trial effectively.

Read part 2 to learn more.

Authors:

Akira Toyama received an M.S. degree in Microbiology from Eastern Washington University. He received a Ph.D. in Molecular and Cellular Biology from University of Southern California, and completed an NIH postdoctoral fellowship in the field of Cardiology and Regenerative Medicine at University of Minnesota Lillehei Heart Institute. Since 2015, he has been at NAMSA and currently works as a Medical Research Manager with primary focus on clinical and consulting work in Japan’s medical device industry.