Development of drug-approval regulations for medical countermeasures against CBRN agents in Japan.

To develop approval regulations for drugs against chemical, biological, radiological, or nuclear (CBRN) agents in Japan, and to help inform arguments about the development of anti-CBRN agents, we analyzed documentation describing approval processes and data for drugs against CBRN agents. Sixteen countermeasure products against 10 CBRN agents have been approved in Japan. Approval schemes were grouped into 3 categories: application for off-label uses, expedited review for antiterrorism measures, and expedited review. Ten drug applications were designated "priority reviews," and the median review time was 4.4 months. No application relied exclusively on clinical trials to expose patients to CBRN threats. Clinical experience with drugs in victims of unexpected exposure was not necessarily important for approval. The United States is the most advanced country in terms of developing medical countermeasure products against CBRN agents. Japan has similarities with the US in approved products and application packages, but there were 3 unapproved products or indications that were approved under the Animal Rule in the US. The Animal Rule might encourage development of a novel product by providing efficacy evaluation in animal studies. The US also has regulations that do not exist in Japan that authorize administration of an investigational drug outside a clinical trial for patients. Introduction of the Animal Rule and expanded access of investigational drugs could contribute to development and approvals of novel countermeasure products and improve an emergency response in a crisis in Japan.