Japan Drug Clinical Trial Update

Successful clinical trials in Japan are key to drug registration. There have been several regulations and guidelines for Japanese clinical trials over the years. Japan’s clinical trial regulations are regulated by the MHLW and outlined in the PMD Act as well as in several other regulations. In 1997, the MHLW issued the – Ordinance on Standards of Implementation of Clinical Studies on Drugs. The PMDA, under the MHLW, is responsible for Japanese GCP standards. Two other important clinical trial regulations include – 1. The Clinical Trials Act for Interventional Research in 2018 and 2. the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in 2021.

Japanese clinical trials are required for new chemical and biological drugs. Foreign drug manufacturers without offices in Japan must choose a Japanese CRO to do the clinical trial and act as their local Japanese ICC. The final responsibility for the clinical trial is still with the overseas Sponsor. As in other global markets, the Investigator must be well respected and qualified to select the patients for the trial.

Some recent updates to Japanese clinical trials are below. First, the MHLW mentioned that Phase 1 studies may not be needed for late-stage global studies, especially for drugs in high demand. Second,  the MHLW is now willing to accept informed consent forms online (eConsent) instead of original paper documents with authentic signatures and stamps. Finally, while real-world evidence can still not be used exclusively for drug approval in Japan, it is now more prevalent for post-market surveillance, observational studies, etc.

Determining the best clinical trial path in Japan can be complicated especially for new drug products. To do this, normally a PMDA consultation is needed. There are several different types of PMDA consultations including pre-Phase 1,2 and 3, pre-NDA, post-marketing surveillance, etc. With respect to a PMDA consultation session for a clinical trial, the PMDA will determine whether the clinical trial the Applicant wants to proceed with will ensure the safety of the patients and the ethical and scientific requirements. To attend a PMDA consultation session you normally need to prepare a detailed information packet (about 50-75 pages) which will vary depending on the type of PMDA consultation session you want to have. Some information packet materials include a briefing document, non-clinical data, a clinical development plan, IB, protocol, informed consent information, etc.

Today, foreign drug companies that want to accelerate their Japanese clinical trials should do a multi-regional clinical trial. By doing this, the drug manufacturer will experience faster, more efficient, and cheaper overall trial costs in Japan than a stand-alone Phase 3 study in Japan. The MHLW has put aside more money and reduced bureaucratic obstacles to encourage multi-regional studies including Japan. About half of the new trials in Japan are part of a multi-regional clinical study compared to about 13% eight years ago. Normally, if the global study is for 500 patients about 10% need to come from Japan – or about 50 patients in about 8- 10 Japanese sites.

In Japan, clinical trials consist of roughly 15% Phase 1 studies, 55% Phase 2 studies, and 30% Phase 3 studies. Experts have said that almost half of the Japanese population will be diagnosed with some cancer. In 2019, there was a new cancer genomic profiling program outlined in a new initiative called — the Cancer Genomic Medicine Plan. Today, about 33% of the clinical trials in Japan are for cancer, about 14% percent for CNS studies, and about 9% for gastro studies.

The future for clinical trials in Japan is bright. Today, the Japan drug lag problem has been reduced, and Japan drug registration only takes about half as long as it did 10 years ago. In addition, next year the MHLW’s budget will grow by double digits to help accelerate drug approvals.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)
Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.