Japanese Regulators Increase Use of “Conditional Approvals” on Drugs

Amid discontent over Japan delay-ridden drug approval process, its regulatory authorities are making greater use of an instrument known as conditional approval. According to the Pharmaceutical Affairs Law, the Ministry of Health, Labor and Welfare (MHLW) can require the marketing authorization holder to conduct more safety and efficacy studies after the initial marketing of the product. If the marketing authorization holder does not comply with the conditions, the MHLW can revoke or amend the approval. One drug with conditional approval was Remicade (infliximab), approved for rheumatoid arthritis in Japan in 2003. After approval, Tanabe Seiyaku was required to conduct a long-term study of Remicade safety and efficacy for all patients taking it. During that study, the number of hospitals that could prescribe Remicade was limited. The results were accepted by the MHLW in 2005.

On July 20th, 2006, Mikio Sasai, a researcher for the Japan Pharmaceutical Manufacturers Association (JPMA), presented an overview of the MHLW use of conditional approvals over the 141 new drug approvals issued from 2000 to 2005. According to his research, the proportion of conditional approvals increased from 30% in the 2000-2002 period to 50% in 2003-2005. Over the entire period, some subcategories of drugs had more conditional approvals, such as orphan drugs (100%) and drugs using foreign clinical trials (50%). He also found that the average development period for drugs with conditional approvals was 63.1 months, or 16 months less than drugs without conditional approvals. At the same time, drugs with conditional approvals appeared to have higher total development costs.

Sasai commented that regulators seemed to commonly use conditional approvals as a tool to help shorten the long gap between approval in the US or Europe and approval in Japan. Often, they used post-approval clinical studies to help confirm that efficacies were similar between Japanese and non-Japanese test populations. Requiring tests on native subjects has long been a cause of delays in the Japanese approval process. The use of conditional approvals is likely to increase in coming years.