History of the Discussion on Ethnic Difference at ICH

This paper describes the history of discussions on ethnic differences at the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use (ICH). The first part of this paper gives a short outline of the purpose, organization, history, decision making process of the ICH. The ICH process consists of five steps. Step 1: Consensus building by Expert Working Group (EWG); Step 2: Confirmation of six-party consensus; Step 3: Regulatory consultation and discussion; Step 4: Adoption of an ICH harmonized tripartite guideline and Step 5: Implementation. Ethnic factors in the acceptability of foreign clinical data ("Ethnic Difference") was one of the 14 topics on Efficacy. The author being one of the members of ICH-E5 EWG took part in the discussion of Ethnic Difference. The second part of this paper, describes the history of the discussion on this topic (from its inception to the finalization of the guideline) focusing on Step 2. A retrospective survey on individual pharmacokinetic data of around 80 drugs approved or under development in the 3 regions was conducted. In drafts 2 and 3, acceptance of phase 1 study only was discussed. But the proposal was opposed by industry members from US and EU. In drafts 4 and 5, the concept of "triage" was introduced and several algorithms were proposed, but finally a consensus could not be reached because the proposal was not so pragmatic. In drafts 7 and 8, the concept of "bridging study" was discussed to solve the problem of conducting phase II and III studies. Again, a consensus could not be reached. After the discussion of the "complete clinical data package" as proposed in drafts 9-12, the bridging study was once again discussed in drafts 13-19. Finally, draft 20 was confirmed and the discussion then moved to Step 3.