The Regulatory Review of Radiotherapeutics: A Japanese Perspective

Abstract

In Japan, systems for the regulatory review of radiopharmaceuticals have lagged behind the rest of the world. Beginning around 2000, the regulatory review of radiopharmaceuticals required a rigorous and time-consuming process, which led to a decrease in the number of applications filed thereafter. As a result, Japan has relied on foreign imports for all its therapeutic—and, for that matter, diagnostic—radiopharmaceuticals. Indeed, all clinical trials during this period have focused on using Japanese subjects to evaluate imported radiopharmaceuticals that have been approved abroad. Historically, no major or international clinical trials had been conducted on Japan-made radiopharmaceuticals until 2018, and few preclinical studies been conducted as well. Therefore, significant knowledge gaps exist with respect to both the research and development (R&D) of radiopharmaceuticals and their regulatory review and approval. In Japan, the disposal of low levels of radioactive materials from laboratories and hospital rooms is regulated strictly by the Act on the Regulation of Radioisotopes (RI) and the Medical Care Act, which has resulted in several problems, including a shortage of Good Laboratory Practice (GLP) facilities. Recently, several new therapeutic agents for radiopharmaceutical therapy (RPT) have been developed. In 2018, for example, National Institutes for Quantum Science and Technology (QST) started a physician-led clinical trial of [⁶⁴Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([⁶⁴Cu]Cu(ATSM)), a Japan-made radiopharmaceutical. Two physician-led clinical trials of alpha-emitting radiotherapeutics have been started as well. In 2022, the Japanese government issued a National Action Plan to wean the country off radiopharmaceuticals from overseas, and progress in the regulation of radiopharmaceuticals is expected soon.