Drugmakers Request Clarification of FDA Flexibility in Rare Disease Drug Development

Drugmakers want the FDA to provide more details and examples of how it would show regulatory flexibility to developers of drugs for rare diseases, saying recent draft guidance is unclear about what may or may not be appropriate.

The Aug. 13 guidance says the FDA may provide flexibility in applying regulatory standards, since certain aspects of drug development that are feasible for common diseases may not be for rare diseases. This flexibility would extend from the early phases of development to design of adequate and well-controlled clinical studies required to demonstrate safety and effectiveness.

In comments to the agency, PhRMA praises the flexible approach but asks for more specific recommendations on issues such as acceptability of single-arm and open-label studies.

PhRMA also suggests the guidance address challenges unique to pediatric rare diseases and provide examples of innovative development approaches that might be used. “It would be helpful if FDA could also provide guidance on additional challenges of developing drugs for rare diseases with an existing therapy,” the group adds, noting superiority clinical trials or naïve patient trials may not always be feasible.

The group was one of 17 to comment on the draft guidance.

Commenters also asked the FDA how sponsors may request pre-IND and other meetings described in the draft guidance. It would be helpful for the FDA to add a section explaining how sponsors may request these interactions, say PhRMA and the International Consortium for Innovation and Quality in Pharmaceutical Development.

PhRMA suggests the FDA outline a process for setting up early and frequent communication outside the standard FDA-sponsor meetings, including appropriate contacts within the agency’s review division and rare disease program.

BIO urges the FDA to give sponsors early and tailored guidance on the timing of planned natural history studies for specific rare diseases.

PhRMA asks that the collection of natural history data be clearly made optional. The group also requests examples of how natural history data could be used not only in the design and analysis of clinical trials but also for product review and approval. — Jonathon Shacat