Presentation PET drug manufacturing and imaging site qualification programs in Japan

脇, 厚生

In Japan, when new PET drugs manufactured in hospitals are applied to be approved by regulatory agency, not PET drug but the PET drug synthesizer is the target of approval as medical devices, and PET drug manufactured in hospitals is out of regulation by Pharmaceutical Affairs Law. PET drug manufacturing in hospitals is recognized simply as use of the medical device, not “drug manufacturing”, and no Good manufacturing Practice (GMP) is applied. This Japan-specific regulation might be very nice from the cost of view, because GMP always needs resources very much. However, from the viewpoint of quality of PET drugs, the appropriate rule of PET drug manufacturing in hospitals was considered necessary. Then, the guidance for PET drug manufacturing in hospitals has been established and published since 1981 from Japan Radioisotope Association, authorized by Japanese Society of Nuclear Medicine (JSNM), but, unfortunately, there have been lack of the thought of quality assurance and the site-qualification program in the guidance. In 2010, in order to harmonize PET drug regulations in Japan and those in US or Europe, JSNM published JSNM-GMP Guideline under collaboration with Ministry of Health Labor and Welfare and Pharmaceutical and Medical Device Agency (PMDA). To assure the compliance of each hospital, National Institute of Radiological Sciences has been appointed as an audit organization under the supervision of JSNM. Based on this JSNM-GMP site-qualification program, the first audit for the hospital has performed at August 22 and 23, 2012, and the hospital was approved as the first hospital under compliance with JSNM-GMP at Jan 25, 2013.The target of JSNM-GMP approval system was initially only clinical research without Investigational New Drug Application (IND), nor the approved PET drugs manufactured by the approved synthesizer. However, as PMDA seemed to recognize this system as a good solution to control the quality of PET drugs manufactured in hospitals, the certificate of compliance issued by JSNM has become essential when a newly approved PET drug synthesizer is installed and used for clinical practice from the timing of the approval of F-18-Florbetapir at 2014 in Japan. Recently, at the application of IND for a PET drug, JSNM-GMP was approved as the suitable regulatory guidance for PET drug manufacturing in the clinical trial with IND.As for the standardization of the image quality, JSNM has issued the standard PET imaging protocols for a number of PET scans including 11C-methionine PET for brain tumor, brain PET with FDG and amyloid agents, and whole-body FDG scan. As well as PET drug manufacturing, the site qualification program by the audit have started by the designated auditing organization, which examines the organizational structure, maintenance and calibration of devices, and the phantom data for specific PET scans on specific PET cameras. Ten of PET drug manufacturing facilities and 15 of PET imaging facilities have been qualified by JSNM, and several sites will apply this qualification program in this year. In here, I introduce mainly JSNM-GMP, the site audit method, good points and difficulties of this regulatory system.
Global standardization and regulatory approval of imaging products, initiated by QIBA (Quantitative Imaging Biomarker Alliance) and the professional societies

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