Reissue of RFA-FD-23-001- Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01 Clinical Trials Required)

The U.S. Food and Drug Administration (FDA), within the Department of Health and Human Services (HHS), administers the Office of Orphan Products Development (OOPD) to stimulate the development of medical products for rare diseases. This funding opportunity represents a reissue of a prior program designed to expand the number of approved treatments for rare conditions. Rare diseases are defined as those affecting fewer than 200,000 individuals in the United States, yet collectively impact millions of Americans. Despite this burden, only a small fraction of rare diseases currently have approved therapies. Through this initiative, FDA aims to accelerate development pipelines and improve clinical outcomes by supporting rigorous clinical trials. The purpose of this Notice of Funding Opportunity is to fund clinical trials evaluating the safety and/or efficacy of orphan products, including drugs, biologics, medical devices, and medical foods. These trials must support either a new indication or a change in labeling for existing products to address unmet medical needs. The program encourages studies across all phases of clinical development, including Phase 1 through Phase 3 trials. Emphasis is placed on generating high-quality data that can directly support regulatory approval or advancement toward approval. Funding is structured as a grant mechanism with a base annual cap of 650000 dollars for up to four years, with the possibility of additional funding up to 250000 dollars per year for innovative trial approaches, bringing the maximum annual total to 900000 dollars. The total project period cannot exceed four years, and continued funding beyond the first year is contingent upon performance, regulatory compliance, and availability of federal appropriations. Cost sharing or matching is not required. Funds must be used to support clinical trial execution, including study design, patient recruitment, data collection, and regulatory compliance activities. Eligibility for this program is broad and includes higher education institutions, nonprofit organizations, for-profit entities including small businesses, state and local governments, tribal governments, and foreign organizations. Applicants must demonstrate the ability to conduct clinical trials, including access to appropriate patient populations, infrastructure, and regulatory approvals such as IND or IDE status where applicable. The principal investigator must have the expertise and leadership capability to manage complex clinical research. The application process requires submission through Grants.gov and eRA Commons, with strict adherence to FDA-specific instructions that may differ from NIH guidelines. While a letter of intent is optional, it is encouraged to assist with review planning. Required application components include a detailed research strategy, clinical protocol, data management plan, patient engagement evidence, and letters of support confirming product availability and site readiness. Applications must comply fully with formatting and submission requirements or risk being rejected without review. Applications are evaluated through FDA’s objective review process based on scientific merit, study design quality, investigator capability, patient engagement, and potential impact on rare disease treatment development. Additional emphasis is placed on innovative trial designs such as adaptive or platform trials, and on the use of shared infrastructure and collaborative partnerships. The program also prioritizes studies that can significantly advance regulatory approval pathways. Key dates follow a recurring annual cycle. The funding opportunity was posted July 11, 2025, with application deadlines on October 21, 2025; October 20, 2026; and October 19, 2027. Optional letters of intent are due approximately one month prior to each deadline. Resubmission deadlines extend into 2027 and 2028, with the final close date of May 16, 2028. Awards are expected to begin as early as July 2026 following review cycles in early spring each year. Applicants are encouraged to engage early with FDA program staff for guidance on study design and regulatory alignment.

Engage FDA early for regulatory alignment; prioritize innovative trial designs such as adaptive or platform trials; demonstrate strong patient engagement and feasibility; ensure IND or IDE readiness before submission