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the Market-Oriented, Sector-Selective (MOSS) talks [2] were set up between government officials of both countries. Although progress has been made and the talks continue, many differences remain. Among these is the fact that Japan insists that drugs developed elsewhere undergo, on the one hand, repeat dose-range finding and pharmacokinetic studies in Japan and, on the other, a comparative drug study. These requirements are purportedly based on the possibility of genetic variation in drug handling between Japanese and non-Japanese patients. |
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There is, concededly, a trend in the United States and the European Union (EU) towards the evaluation of pharmaceuticals in an increasing number of subgroups [3]. Differences noted in the dose response or ADME (absorption, distribution, metabolism, excretion) data may well suggest that additional clinical investigations are necessary. However, where no differences are noted it is difficult to justify a repetition of the Phase III program within the confines of technical registration. |
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The MOSS initiative was spearheaded by representatives from the U.S. Department of Commerce, since the Japanese requirements were perceived as a barrier to free and fair trading. These representatives were not, however, equipped to debate the scientific aspects of these requirements. With the advent of the International Conference of Harmonization (ICH) [4,5] movement, it is hoped that this technical group could address such matters. |
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Within the ICH process there are five steps defined in the path to harmonization. Once selected for harmonization, the topic is worked on by the appropriate Expert Working Group (Step 1) and their deliberations are sent to the ICH Steering Committee (Step 2) who consult the participating regulatory bodies (Step 3) before submitting final recommendations to the three regulatory groups (Step 4) for incorporation into the regulations (Step 5) [6]. |
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As in most countries, the Japanese regulatory decision-making process is less transparent than that in the United States. However, this impediment to registration like those posed by the drug development process and regulatory requirements, will lessen as the United States, EU, and Japan increasingly harmonize drug approval. Although the major impetus to harmonization may be improved commercial access for global marketing, other benefits include earlier availability of new medicines and reduced sacrifice of animals for duplicate studies to satisfy national variations in regulatory protocols. Thus the Japanese requirements for drug approval, like those of other nations, appear to be passing a threshold of significant transition. |
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II. The Regulatory Process |
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The Japanese Pharmaceutical Affairs Law (PAL) covers pharmaceutical development for registration and matters pertaining to manufacturing, licensing, |
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