For new medical devices and pharmaceuticals for which there are no equivalent products already approved in Japan, clinical trials are required. This rule also applies to previously approved products to which improvements or modifications are made which could potentially improve the efficacy or expand the scope of the product. Clinical trials must be conducted under strict Good Clinical Practice (GCP) standards, and must be followed by standard Post Marketing Assessment (PMA) reporting and a follow-up program. As a general guideline, a typical clinical trial requires a minimum of two clinical trial sites with at least 30 test subjects at each location, but this is subject to the interpretation of the examiner, who often vaguely states “enough trials should be conducted to ensure the safety and efficacy of the product.”
With respect to medical devices, until relatively recently foreign clinical data was not acceptable in Japan at all. This changed in 1986, when the U.S. and Japan negotiated and signed what is commonly referred to as the “MOSS” (Market-Oriented, Sector-Selective) agreement. Before the MOSS, MHLW required that all clinical testing of medical devices (and pharmaceuticals) be done in Japan on Japanese subjects. For foreign firms, this requirement meant costly duplication of clinical trials and delayed the introduction of new products into the Japanese market.
After the MOSS agreement was signed, foreign clinical test data was officially accepted in Japan, except when immunological and ethnic differences between Japanese and non-Japanese subjects made local trials necessary. Since then, the percentage of foreign clinical test data found to be acceptable has increased gradually each year, but still less than 20% of those who apply are accepted. Although scientific reasons for requiring local testing can be justified, there are instances where non-scientific motives are believed to play a role, possibly in order to provide domestic manufacturers an opportunity to “catch-up.” Although very difficult to prove, it is believed that such practices, while rare, do sometimes occur in the medical device industry.
Given the MHLW’s power, it is often pointless to argue with such a situation. A better strategy is to include Japanese patients in your clinical trials from the beginning. An even better approach would be to define what the Japanese GCP requirements are for the clinical trials to be conducted and to obtain a preliminary ruling that the planned clinical trial test protocols are acceptable. The safest option, of course, would be to conduct a limited number of clinical trials in Japan. With the Japanese medical community involved, the MHLW would be hard-pressed to ignore such clinical test data.