Regarding the conduct of clinical studies to collect data to be submitted with approval applications for new drug manufacturing or import, the Pharmaceutical Affairs Law and the GCP (MHW Ordinance No.28, March 27, 1997) require that the MHLW be notified of the study protocol beforehand and provide various requirements to be met by the sponsor when requesting medical institutions to perform clinical studies.
Compared with the former GCP, the following points are conspicuous: a) the scope of the GCP has been extended to cover post-marketing clinical studies, b) the role and responsibilities of sponsors such as pharmaceutical companies have been clarified and strengthened, and c) medical institutions performing clinical studies are obliged to comply with the GCP.
When sponsors request clinical studies they must have obtained adequate data concerning the safety, efficacy and quality from previous nonclinical studies and other human studies which support as much as possible the objectives of the study, and the subject population, route of administration, dosage and ad-ministration, the time of exposure, and observations and evaluation items to be applied in the proposed study, as well as support for the ethical and scientific suitability of the study. All procedures must be specified in writing.
Sponsors must request the study sites to inform the subjects adequately about the contents of the clinical study and obtain their written informed consent to participate in the study. The sponsor must also take the necessary measures beforehand to provide compensation for any health impairment caused by the investigational product. The range of the GCP covers not only clinical studies on patients, but also Phase I studies on healthy volunteers, bio-equivalence studies on humans, studies on added indications for approved drugs and post-marketing clinical studies conducted after the drug goes on the market.
According to the new GCP, when a clinical study is requested, a contract for clinical trials can be concluded only when 30 days have passed from the initial notification of the study protocol is received by the Evaluation Center (at least 2 weeks for subsequent notifications).
The sponsor must report to the authorities any severe adverse reactions or infections which occur during the study, and the authorities may undertake on-site inspections concerning GCP compliance in the sponsor's facilities and the medical institution performing the study when problems arise during the study.
At the time of the clinical study protocol notification, a system by which OPSR (KIKO) reviews the contents of the initial notification at the request of the MHLW is now specified by law, and a "clinical trial consultation system" in which OPSR (KIKO) gives guidance and advice concerning study protocols has also been established
Quality Control
The requirements for manufacturing control and quality control methods in pharmaceutical plants (GMP software specifications) are specified in "Regulations for Manufacturing Control and Quality Control of Drugs and Quasi-Drugs" in the MHW Ordinance No. 16, March 12, 1999). The requirements for manufacturing control and quality control methods for drug substance should be referred to the Guidelines on GMP for Drug Substance (Notification No. 1200 dated November 2, 2001) which concretely specifies 20 requirements concerning manufacturing and control of drug substance, including quality control, buildings and facility, validation, as agreed in the ICH5 held in San Diego, California, USA in November 2000.