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Rare Disease Endpoint Advancement Pilot Program Frequently Asked Questions

Q: What is the Rare Disease Endpoint Advancement (RDEA) pilot program?

A: The RDEA Pilot Program is a U.S. Food and Drug Administration pilot meeting program, which supports the goal of advancing and facilitating the development and timely approval of drugs and biological products for rare diseases, including rare diseases in children. Under the seventh iteration of the Prescription Drug User Fee Amendments (PDUFA) VII, FDA agreed to establish a pilot meeting program for the development of novel efficacy endpoints in rare disease drug development programs for sponsors with an active investigational new drug (IND) or pre-IND for the rare disease, or sponsors who do not yet have an active development program but have, or are initiating, a natural history study where the proposed endpoint is intended to be studied.

This program offers selected sponsors an opportunity for increased engagement with FDA experts from the Center for Drug Evaluation and Research and/or Center for Biologics Evaluation and Research to discuss novel efficacy endpoints intended to establish substantial evidence of effectiveness for a rare disease treatment. The pilot program period will run through September 30, 2027.

Q: Which members of the FDA are involved in interacting with the Sponsor as part of the RDEA Pilot Program?

A: Sponsors whose RDEA proposals are admitted into the RDEA pilot program will have the opportunity to interact with interdisciplinary FDA experts in endpoint development as well as the associated review division. The types of interdisciplinary experts will depend on the nature of the proposed novel endpoint.

Q: Is there a type of question that can be discussed during RDEA pilot program meetings that exceeds what a sponsor can discuss with the FDA review division during a formal IND meeting regarding endpoints?

A: Any sponsor whose RDEA proposal is admitted into the RDEA pilot program will have the opportunity for increased interaction with the FDA to discuss issues associated with their proposed rare disease novel endpoint. For each RDEA proposal that FDA admits into the pilot program, the agency will conduct an initial meeting and up to three follow-up meetings.

Q: What is the difference between the RDEA pilot program and Drug Development Tool (DDT) qualification programs?

A: Sponsors seeking a series of focused meetings to develop a novel endpoint for a rare disease(s) should consider the RDEA pilot program. RDEA includes a series of focused meetings to discuss novel efficacy endpoints for rare disease treatments and follows a different process than the DDT qualification process. The RDEA program does not result in qualification of an endpoint. The DDT program should be used by sponsors seeking qualification for DDTs such as clinical outcome assessments (COAs), biomarkers, or animal models for use under the Animal Rule.

DDTs are methods, materials, or measures that have the potential to facilitate drug development. To support DDT development efforts, FDA established qualification programs for animal models for use under the Animal Rule, biomarkers, and COAs. Qualification is a conclusion that within the stated context of use (COU), the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review.

As the agency stated in its November 2020 guidance, Qualification Process for Drug Development Tools Guidance for Industry and FDA Staff, seeking qualification for a specified COU is voluntary. DDTs that have not been qualified or that are qualified for a different COU may still be used in regulatory applications, when scientifically appropriate for a specific application, based on agreement with the appropriate review division or office. Upon agreement with the review division, such use of a DDT within a regulatory application, however, is not considered qualified under section 507 of the Federal Food, Drug, and Cosmetic Act.

Q: What types of sponsors can submit a proposal for the RDEA pilot meeting program?

A: For the purposes of the RDEA Pilot Program, consistent with 21 CFR 312.3, a sponsor is a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. Therefore, various types of sponsors can apply to participate in the pilot. However, an RDEA proposal must meet the program eligibility criteria as stated on the RDEA Program webpage and in the October 27, 2022, Federal Register notice announcing the program.

Q: When would FDA recommend interacting with the FDA through the RDEA pilot program instead of interacting with the FDA review division through the IND?

A: The RDEA pilot program is in addition to other interactions with the FDA review division through the IND submission process. Sponsors seeking a series of focused meetings to develop a novel endpoint for a rare disease(s) may consider submitting a proposal to the RDEA pilot program.

Q: When in the drug development program should the sponsor submit an RDEA pilot program proposal?

A: Sponsors should submit RDEA pilot program proposals as early as possible in the design of efficacy trials with active pre-INDs or INDs, or a natural history study for a rare disease drug treatment.

Q: When is FDA accepting proposals for the RDEA pilot program? When are the submission deadlines?

A: FDA will begin accepting proposals on a quarterly basis for admission into the RDEA Pilot Program on July 1, 2023. The quarterly deadlines for submitting RDEA proposals are March 31, June 30, September 30, and December 31. As the PDUFA VII period will end September 30, 2027, the last quarterly deadline for submitting an RDEA pilot proposal under PDUFA VII is June 30, 2027.

Q: How many proposals will be accepted into the RDEA program?

A: FDA will accept a maximum of one proposal for proposals submitted by September 30, 2023, the end of the fourth quarter of fiscal year 2023 (FY23). Between FY24 and FY27, FDA will accept up to one proposal per quarter with a maximum of three proposals per fiscal year.

Q: Can multiple INDs be referenced in an RDEA proposal to explicitly demonstrate and discuss the applicability of an approach across therapeutic areas?

A: To be considered for admission to the RDEA Pilot Program, an RDEA proposal must meet program eligibility criteria, including, generally, that the sponsor has an active pre-IND or IND for a rare disease. While it is possible that an RDEA proposal for a specific development program may have application to another development program, sponsors should reference one IND under which the proposed novel endpoint would be developed, and clearly explain how development of the novel endpoint would be applicable to other INDs.

Q: Where in the eCTD (which module) should the sponsor submit the RDEA proposal?

A: Please submit the RDEA program proposal request in eCTD module 1.6.1 Meeting request.

Q: Per the FDA’s RDEA Pilot Program Webpage, a proposal “should include a one to two page(s) executive summary and be no longer than 12 pages long.” Could the FDA clarify if the 12-page limit excludes the Title Page, Table of Contents, and Reference pages?

A: The RDEA proposal 12-page limit excludes the Executive Summary, Title Page, Table of Contents, and the Reference page.

Q: Will FDA give preference to certain rare disease novel efficacy endpoint proposals?

A: FDA will give preference to proposals that have the potential to impact drug development in rare disease more broadly, such as one that uses a novel approach to develop an efficacy endpoint or an endpoint that could potentially be relevant to other rare diseases. (Endpoints are measurements of what happens to people in a clinical trial.) FDA will also give preference to proposals that reflect a range of different types of endpoints. For surrogate endpoint proposals, FDA will give preference to those with novel approaches for collecting additional clinical data in the pre-market stage to advance the validation of these endpoints. (If a sponsor is proposing to develop a surrogate endpoint as part of a rare disease application, FDA encourages participation in a prior Type C Surrogate Endpoint meeting.)

Q: Will FDA publicly disclose that the agency has admitted a sponsor’s proposal into the RDEA pilot program?

A: No. If the sponsor chooses to publicly disclose that it has been admitted into the RDEA Pilot Program, FDA may reference the sponsor as a participant in discussions about the RDEA Pilot Program. FDA will share the overall number of RDEA Pilot Program proposals made and the number of proposals the agency selected for admission into the pilot program.

Q: What are the timelines associated with the RDEA Pilot Program?

A: FDA will notify the sponsor with a final selection decision no later than 60 days following the end of the fiscal year quarter during which the RDEA proposal is submitted. After a sponsor is admitted into the RDEA pilot program, each RDEA meeting will be scheduled within 45 days following FDA’s receipt of the sponsor’s meeting request and complete briefing document. Conduct of up to four RDEA meetings does not need to fall within a specified timeframe after a sponsor’s proposal is admitted into the RDEA pilot program.

Q: Does the sponsor have an opportunity to review and agree to any content to be disclosed? When in the process do public disclosures occur?

A: FDA and the sponsor will discuss and agree on the disclosure elements before the sponsor is admitted into the RDEA pilot program. If FDA and the sponsor are unable to reach agreement on elements for public disclosure, that proposal will no longer be considered for the RDEA pilot program, and the Agency will proceed with an alternate submission. Once the disclosure agreement is signed and the proposal is admitted to the RDEA Pilot Program, public disclosure of the information learned through the endpoint development program may occur in various fora such as guidance documents, public-facing website, or public workshops. When feasible, FDA will notify a sponsor in advance when the sponsor’s program is the planned focus of a public discussion.

Visit Rare Disease Endpoint Advancement Pilot Program for more information about the program.

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