International Conference on Harmonization: Is the bar being raised too high?

Getting a drug to market requires a complex series of evaluations and regulatory reviews to ensure that it meets quality, safety and efficacy standards. Approval of new drugs is done by national governments, which set standards. The United States, Japan, and the European Union have attempted to harmonize their standards through the creation of the International Conference on Harmonization (ICH), an initiative of drug regulatory authorities and research-based pharmaceutical industries. The goal of harmonization is to reduce drug development and regulatory review times. The ICH is tightening requirements beyond those stipulated by the World Health Organization (WHO). The quality, efficacy and safety requirements that constitute the ICH guidelines deal specifically with drug development in a wealthy market, where cost is not a major issue and where safety is defined as near-zero risk. For neglected diseases, cost is a major issue, and the risk-to-benefit ratio in terms of quality, efficacy and safety should be put into the perspective of the gross public health failure of having no treatment at all. These more stringent ICH guidelines raise costs and present barriers to drug development, particularly for small or medium-sized companies in developing countries. The risk is that the bar will be raised so high that only drugs developed in the industrialized world will be able to be marketed internationally. This will seriously hamper the development of R&D capacity in developing countries, which has been identified as a necessary component in the long-term solution to the R&D crisis. This potentially negative public health implication needs to be carefully weighed against the possible benefits of raising R&D requirements, which some have argued would be marginal and of little value to patients.7 Many questions remain unanswered on the implications of the ICH guidelines. An independent and thorough technical review of ICH guidelines should be undertaken by WHO. If ICH is to become a global standard, it must be reexamined to ensure that it meets the needs of both developing and developed countries.