This guidance assists sponsors of drug and biological products intended to treat or prevent rare diseases in conducting more efficient and successful development programs through a discussion of selected issues commonly encountered in rare disease drug development. Although similar issues are encountered in other drug development programs, they are frequently more difficult to address in the context of a rare disease with which there is often little medical experience. These issues are also more acute with increasing rarity of the disorder. A rare disease is defined by the Orphan Drug Act of 1983 as a disorder or condition that affects less than 200,000 persons in the United States. Most rare diseases, however, affect far fewer persons.
This guidance addresses the following important aspects of drug development:
- Adequate description and understanding of the disease’s natural history
- Adequate understanding of the pathophysiology of the disease and the drug’s proposed mechanism of action
- Nonclinical pharmacotoxicology considerations to support the proposed clinical investigation or investigations
- Reliable endpoints and outcome assessment
- Standard of evidence to establish safety and effectiveness
- Drug manufacturing considerations during drug development
Early consideration of these issues allows sponsors to efficiently and adequately address them during the course of drug development, from early exploratory studies to confirmatory efficacy and safety studies, and to have productive meetings with FDA. These and other issues, as they apply to all drug development programs, are also considered in FDA and International Conference on Harmonisation (ICH) guidances.