The US Food and Drug Administration (FDA) has issued draft guidance, Rare Diseases:Common Issues in Drug Development, to assist sponsors of drug and biological products intended to treat or prevent rare diseases in conducting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. The draft guidance specifies that although similar issues are encountered in other drug-development programs, they are frequently more difficult to address in the context of a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.
The draft guidance addresses key aspects of drug development: drug manufacturing considerations during drug development; description and understanding of the disease’s natural history; 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; and standard of evidence to establish safety and effectiveness.
With respect to manufacturing, the FDA recommends in the draft guidance that sponsors consider the potential development of the manufacturing process in the entire drug-development program early, including which nonclinical and clinical studies are intended to be conducted with each change in the manufacturing process, and whether bridging studies will be needed. The draft guidance also says that sponsors should design adequate testing procedures early and implement them in a timely manner to mitigate delays. The guidance also specifies that changes in the manufacturing process should be implemented as early as feasible to decrease the potential for delay-causing drug differences or, if there are differences, to allow time to evaluate their effects. Given the wide variety of drugs, some of which are complex, the FDA advises sponsors to consult existing manufacturing guidances.
Drug development for orphan diseases has become an important part of new drug development. In 2014, 41% (17 of 41) of new molecular entities approved by the FDA's Center for Drug Evaluation and Research were for rare diseases.