Foreign clinical trials

How does the MHLW of Japan treat foreign clinical trial data in its approval process ... 

Japan has adopted the ICH GCP guidelines for clinical trials since 1997. It upholds the Helsinki Declaration to ensure the rights, welfare, and privacy of subjects are protected in clinical trials. Japan accepts foreign clinical trials, but bridiging trials may need to be performed to take into consideration effects of ethnic factors. 

Uchida K. 1988. Acceptability of foreign clinical trial data in Japan . Drug Inf. J. 22 103-108. 

Facilitate the evaluation and acceptance of foreign clinical trial data by promoting common understanding of general principles and approaches, and also the definition of relevant terms. 

Foreign clinical trials with lovastatin began in April 1980 but were suspended just 5 months later because, according to a Merck spokesman, a similar compound had caused a toxic reaction in animals at another lab. Although it was not announced at the time, the similar compound was Sankyo s mevastatin, which had been quickly withdrawn after intestinal lymphomas were found in 50 percent of laboratory dogs undergoing tests with the drug. 

Foreign clinical results are acceptable except in areas where there are immunological and ethnic differences between Japanese and foreigners. The ethnic factors are divided into two components intrinsic factors such as racial factors and physiological differences and extrinsic factors, which include cultural and environmental issues. In these cases, the MHLW may require that some bridging comparative clinical trials be performed with dose ranging protocols. This will enable absorption, distribution, metabolism, and excretion studies to be carried out on Japanese individuals and provide better dosage and indication for the Japanese people. The MHLW also requires that application be accompanied by one year of real-time stability data and that sterility test results be included. 

Foreign drugs are required to have import registration. Foreign drug manufacturers and distributors file for examination and registration of their products with relevant data and documents. Clinical trials may need to be conducted based on evaluation by the Center for Drug Evaluation (CDE) (see Section 8.5). 

The bill would have permitted the FDA to dispense with the requirement that manufacturers turn over voluminous raw data from clinical trials. Manufacturers instead would have delivered condensed, tabulated, or summarized data—just as they do now in submissions to the FDA s foreign counterparts—and the agency would have retained authority to obtain additional material when needed. 

The majority of the proteins in clinical trials in August 1991 were monoclonal antibodies for treatment of sepsis or neoplasia (see Immunotherapeutic agents). Monoclonal antibodies are derived in most cases from mouse cell lines. This leads to the problem that the antibodies are recognized as foreign by the human immune system. Research efforts are directed toward humanizing antibodies so that these molecules can escape immune surveillance, for example, by the systematic replacement of murine-specific peptide sequences with human homologues while still maintaining the... 

In this section, a description and analysis of any additional information obtained by the applicant from any source, foreign or domestic, that is relevant to the evaluation of the efficacy and safety of the product should be included. It may include results of controlled or uncontrolled clinical trials of uses of the drug other than those claimed in the application, commercial marketing experience, and reports in the literature or otherwise obtained, other than those cited in the controlled trials and uncontrolled trials sections of the clinical data section. 

Adverse Events, Including Laboratory Abnormalities, from Sources Other Than Clinical Studies. All sources of adverse events other than clinical trials, including foreign marketing experience and epidemiologic studies, should be summarized. The procedures used to obtain this information should be described. 

Data from clinical studies in foreign countries are, in principle, acceptable in the USA, as long as the trial protocols comply with the US regulations and GCP standards. However, as in most countries, at least a part of the studies will have to be performed or repeated in the USA because, for example, the population may be different and the medicinal practices differ. Besides for these reasons, clinical trials are frequently conducted locally because the data tend to be more convincing. 

Acceptance of data on clinical trials or drugs conducted in foreign countries. 

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