On January 26, 2019, FDA issued draft guidance on Rare Diseases: Common Issues in Drug Development. The FDA intends the guidance to help sponsors conduct more efficient and successful development programs for drug and biological products for rare diseases affecting fewer than 200,000 people in the United States. While they may be encountered in other drug development programs, the issues discussed in the guidance are often more difficult to address in the context of rare diseases due to limited medical and scientific knowledge, natural history data, and drug development experience.

This draft guidance revises and replaces the previously published draft guidance of the same name, issued in August 2015. The revised draft guidance updates the guidance’s natural history studies section. In this section the guidance provides both general principles to enhance the usefulness of natural history studies in rare disease drug development and a discussion of various types of natural history studies. The revised draft guidance also adds a safety section. The safety section notes that when reviewing a drug’s safety assessment and profile in the context of rare diseases, FDA considers the feasibility challenges posed by the limited number of patients with the disease. This section provides several approaches for augmenting the safety assessment for a drug in this context. In addition, the revised draft guidance adds an additional considerations section, which addresses participation of patients, caretakers, and advocates; expedited programs; and pediatric considerations.

Further, the guidance highlights the importance of the following elements in development programs for rare diseases: adequate description and understanding of the disease’s natural history, adequate understanding of the pathophysiology of the disease and the drug’s mechanism of action, nonclinical-pharmacotoxicology and human toxicology considerations to support the proposed clinical investigation(s), selection or development of outcome assessments and endpoints, evidence to establish safety and effectiveness, drug manufacturing considerations during drug development, participation of patients, caretakers, and advocates in development programs; and interactions with FDA. FDA notes that early consideration of these issues will allow sponsors to efficiently and effectively address them and have productive meetings with FDA.

Readers are encouraged to read the draft guidance, also available on FDA’s website.