Medical Devices in Japan: Standards and Guidelines for GCP and Clinical Trials

On the surface, Japanese GCP guidelines seem fairly standard and straightforward. Basic duties and requirements for the medical institution(s) at which trials are held, the physicians involved, the Institutional Review Board, and the Trial’s Sponsor are very similar, if not identical, to U.S. standards. Informed consent and other rights of the patients, record retention, and other routine issues are also addressed in a familiar manner.

Perhaps the biggest difference between the U.S. and Japanese systems is the role of the Chief Investigator. When Clinical Trials are conducted in Japan, the Chief Investigator is the physician responsible for supervising the entire course of the trial, including supervising any other physicians that may be involved. The Japanese Chief Investigator also has a role when clinical trials are conducted outside of Japan. Even if foreign clinical data has been accepted on a preliminary basis by the MHLW, the final hurdle is to get a Japanese doctor — the “Chief Investigator†— to sign off. Once such a doctor has issued a final opinion expressing compliance and efficacy of the product, that doctor becomes “responsible†for the clinical data. It must be stressed that only a Japanese doctor in Japan can fill the role of “Chief Investigator†— Japanese doctors practicing in the U.S. are not acceptable for this purpose.

The most important thing to understand with regard to Japanese clinical trials is that the regulations governing clinical trials and GCP standards remain open to interpretation — few things are set in stone. The exact number of test subjects and trial sites is subject to the interpretation of the examining officer of the MHLW and varies with product and examiner. Decisions on a company’s clinical trials can vary widely, depending on which MHLW examiner you speak to, his or her mood, and other subjective factors. Different examiners may “recommend†vastly different numbers of case studies for exactly the same product. Similarly, after giving a preliminary opinion, the same examiner may arrive at a completely different conclusion days later, and he or she may decide more studies are needed, even if no new information is presented. Most frustratingly, a company can never (or at least should never) say to a MHLW examiner, “but you said…last week,†because the examiner will likely respond: (1) “you must have misunderstood what I said;†or (2) “you didn’t explain it properly the last time;†or (3) “maybe we better review the entire issue from scratch…â€

In sum, it takes skill and diplomacy to work with the bureaucracy of the MHLW, and it can be incredibly difficult to get a MHLW official to commit to anything. Moreover, the MHLW does not produce official guidelines for clinical trials. If pressed, officials will point you in the direction of the Pharmaceutical Affairs Law (PAL) and related documents and rulings. However, these documents are generally only available (at least officially) in Japanese, never address the intricacies of a trial, and as with any legal document, everything in these documents is subject to interpretation — and the MHLW’s interpretation is the only one that really matters.