FDA, Rare Diseases, Regulatory

FDA revises draft guidance on rare disease drug R&D

The FDA has updated a 2015 draft guidance on rare diseases, with new information gleaned since the original draft was released.

Among the revisions to the 24-page draft guidance, according to the FDA, are updates to the natural history studies section, the inclusion of issues for evaluating and validating biomarkers as surrogate endpoints, a discussion of additional flexibility on the non-clinical aspects of the evaluation of novel drug compounds, the addition of a section describing the evaluation of safety questions and added information on changes to drug substance or drug product manufacturing process with clarification on areas of additional flexibility.

Scott Gottlieb

“The revised draft guidance issued today discusses select issues commonly encountered in rare disease drug development. While similar issues often also come up for common diseases, they’re frequently more difficult to address in the context of a rare disease for which there’s often limited medical and scientific knowledge,” FDA Commissioner Scott Gottlieb said.

Many of the updates are in direct response to feedback that the FDA received on the first draft, Gottlieb said. For example, there’s an updated section describing the use of information about natural history as clinical comparators and additional information on the use of historical controls and early randomization.

In addition to the changes, the 10 sections of the guidance deal with natural history studies; disease pathophysiology, clinical manifestations and identification and use of biomarkers; nonclinical studies; efficacy endpoints; evidence of effectiveness and safety; pharmaceutical quality considerations; additional considerations (such as expedited and pediatric considerations); and interactions with the FDA.

The agency also plans to hold a public meeting to obtain new patient and caregiver perspectives on the impacts of rare diseases on daily life. The meeting will assess common experiences that may help the FDA and medical product developers further understand and advance the development of treatments for rare diseases, with the potential for enabling novel endpoints or trial designs that focus on commonalities across a variety of rare diseases.


First published here. Regulatory Focus is the flagship online publication of the Regulatory Affairs Professionals Society (RAPS), the largest global organization of and for those involved with the regulation of healthcare and related products, including medical devices, pharmaceuticals, biologics and nutritional products. Email news@raps.org for more information.


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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
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Atlas Venture Cambridge, MA

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