<b>「医療上の必要性の高い未承認薬・適応外薬検討会議｣において検討された適応外薬の申請形態</b>

Abstract

The Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs (the Committee) was launched in 2009 to address the issue of unapproved drugs or off-label uses of drugs that are approved in the other developed countries but not in Japan. The Committee evaluates whether a proposed drug or treatment meets high medical needs by reviewing the formal petitions submitted by patient advocacy groups, academic societies, and pharmaceutical companies. Based on the review of the Committee, the Ministry of Health, Labour and Welfare (MHLW) determines the mode of regulatory authorization process. Especially for unapproved use of an approved drug, the MHLW decides whether the use meets the criteria for “abbreviated application of publicly known but unapproved indication”. If applicable, the marketing authorization holder can submit a dossier for the abbreviated application, which includes existing data generated from clinical practice without additional clinical trial data. If the drug does not meet the criteria, new data from additional registered clinical trials are usually required. As of June 2014, the MHLW gave decisions on the mode of regulatory process for 174 petitions submitted to the Committee during the first and the second public recruitments for drug development. We reviewed these documents to determine which factors were associated with the decision of abbreviated application. Among 59 petitions received in the second recruitment providing detailed background and reasons necessitating the development, 21 petitions provided the data of domestic investigator-initiated prospective trials. Seventeen of the 21 petitions were determined to be valid for abbreviated application, indicating a strong association with the presence of domestic clinical trial data. On the other hand, regulatory approval in other developed countries, despite being a prerequisite for abbreviated application, was inversely associated with actual designation of the abbreviated application. The clinical data required for designation of the abbreviated application are not as well controlled as one derived from conventional clinical trial data, and consequently are expected to have a lower evidence level. The abbreviated application strategy should be cautiously employed while the issue of drug lag is being resolved gradually in Japan.