BIO praised a Food and Drug Administration (FDA) initiative targeting more tailored, patient-centered, and predictable development of rare disease drugs, while recommending ways to make it happen, at an Oct. 28 public meeting.
The FDA’s Fit-for-Purpose Rare Disease Framework Initiative seeks to accommodate the unique challenges of developing and reviewing drugs for rare diseases.
Compared to other conditions, rare diseases have small patient populations, limited natural history data, and disease heterogeneity, and they pose challenges in generating conventional clinical evidence. Attracting investment for rare disease drug development can be difficult due to the constraints of small patient populations and certain regulatory challenges.
For all these reasons, 95% of rare disease patients still lack an approved treatment, though rare disease impacts over 30 million Americans, making efforts to ease drug development both welcome and urgently needed.
“We strongly support FDA’s effort today,” E’Lissa Flores, Senior Director, Science and Regulatory Affairs at the Biotechnology Innovation Organization (BIO), told the public meeting. “BIO sees this Framework as an opportunity to translate fit-for-purpose principles into consistent practice, with greater predictability, early alignment, patient input, and appropriate consideration of uncertainty, while maintaining scientific rigor and FDA standards.”
Led by FDA’s Rare Disease Innovation Hub—in partnership with the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and the Office of the Commissioner—the initiative was announced Oct. 14, and the public meeting was called as the first major step in its development.
“BIO’s members appreciate that FDA is seeking input before moving forward and welcome the opportunity to provide feedback through this public meeting and through written comments until Dec. 11,” Flores said.
FDA’s basic principles for the initiative
FDA said the following principles would be instrumental in developing the Fit-for-Purpose Rare Disease Framework Initiative:
- “Providing greater clarity, consistency, and predictability in regulatory decision-making through tailored guidance and transparent communication.”
- “Embedding the patient’s voice both early, and at clearly defined milestones, in the drug development and review process.”
- “Further leveraging external expertise to support customization of regulatory review.”
- “Building shared resources, robust training, and institutional knowledge on rare disease drug development and review.”
- “Applying risk-based approaches, particularly to chemistry, manufacturing, and controls review and pre-approval inspections.”
- “Championing the use of cutting-edge science, novel methods and innovative statistical approaches in rare disease drug development.”
BIO’s initial recommendations
In her comments at the public meeting, Flores highlighted some emerging themes for consideration when implementing the initiative:
- “BIO encourages FDA to apply fit-for-purpose evidentiary approaches that maintain scientific rigor while reflecting the realities of rare disease,” Flores said. To do this, FDA should consider all available evidence—such as natural history, biomarker, and real-world evidence—and apply it consistently across all FDA centers and review teams.
- The fit-for-purpose principles should extend to the Chemistry, Manufacturing and Controls (CMC) portion of an investigational new drug (IND) application, as this component is also different for rare diseases. “BIO supports risk-based approaches to the timing and generation of CMC evidence that recognize the realities of rare disease development while maintaining appropriate product-quality standards,” Flores said.
- The Framework presents an opportunity to move innovation into regulatory practice. FDA should seek to advance methods from pilots and workshops into routine regulatory use and for updating guidance.
- Early and ongoing FDA-sponsor alignment is essential, through early conversations about expectations that take place before an IND. “That includes early dialogue around endpoints, evidence-generation strategies, trial design, preclinical and CMC expectations, and acceptable uncertainty,” according to Flores.
- “Patient input should be embedded throughout the development lifecycle,” Flores emphasized. This means FDA should clarify when patient input should be provided, how it will be considered, “and how patient engagement, patient experience data, and patient preference information can appropriately inform regulatory decision-making.”
- Consistent implementation across review divisions and FDA centers is essential. “The Rare Disease Innovation Hub can help by integrating expertise across the Agency, sharing successful approaches and best practices, and facilitating external expertise to support reviewer education and ensure decisions reflect the latest science,” Flores said.
“BIO looks forward to continuing its engagement with the FDA to advance fit-for-purpose regulatory approaches that maintain scientific rigor while supporting the timely development of safe and effective treatments for patients with rare diseases,” Flores concluded. BIO plans to work closely with its members to submit detailed comments and key recommendations to docket in support of FDA’s development and implementation of the Framework.
FDA has issued a Request For Information on the initiative and is accepting written comments through the Federal Register until Dec. 11.
(Photo by David Richfield, Wikimedia Commons.)
