Regenerative Medicine Innovation Project (RMIP) Investigator-Initiated Clinical Trials (UG3/UH3 Clinical Trial Required) | RFA HL 22 014

Opportunity Information: Apply for RFA HL 22 014

The Regenerative Medicine Innovation Project (RMIP) Investigator-Initiated Clinical Trials (UG3/UH3, Clinical Trial Required) opportunity (RFA-HL-22-014) is an NIH cooperative agreement designed to move adult stem cell-based regenerative medicine interventions into human testing and to address practical, well-known roadblocks that slow the field. NIH Institutes and Centers participating in RMIP are coordinating with the U.S. Food and Drug Administration (FDA) to encourage applications that are both scientifically strong and operationally realistic, with an emphasis on producing credible safety and early efficacy evidence that can support the longer path toward approved therapies. This program was created in line with the 21st Century Cures Act, which set out a statutory push to accelerate regenerative medicine development while maintaining rigorous standards for clinical evidence and participant protections.

A central feature of the program is its two-stage (bi-phasic) structure using the UG3/UH3 mechanism. The UG3 phase functions as a milestone-driven planning and start-up period where teams finalize critical elements needed to responsibly launch a trial, such as clinical protocol readiness, site preparation, manufacturing and quality systems, and regulatory alignment. The UH3 phase is the later stage that supports full clinical trial execution once predefined milestones are met. Because this is a cooperative agreement rather than a standard grant, applicants should expect substantial NIH program involvement, including milestone negotiation, close progress monitoring, and active engagement intended to improve the probability that a complex, high-stakes clinical trial can be completed on time and with interpretable results.

The FOA targets Phase I and later clinical trials and is explicitly focused on adult stem cell-based regenerative medicine products. A key expectation is that proposed interventions are not purely exploratory concepts but have already gone through appropriate product development and preclinical testing and are demonstrably ready to advance into clinical trials. In practice, that means the application needs to show a clear scientific rationale for testing in humans, a credible risk-benefit justification, and evidence that the product and its manufacturing approach are mature enough to support clinical-grade administration. The program is especially interested in innovative projects that propose concrete solutions to recurring challenges in regenerative medicine development, such as consistent product characterization, scalable manufacturing under quality controls, clinically meaningful outcome selection, safety monitoring strategies tailored to cell-based interventions, and trial operations that can handle complex administration or follow-up needs.

Applications must meet the NIH definition of a clinical trial and align with the mission of at least one participating NIH Institute or Center. The FOA signals that NIH is looking for applications that go beyond the scientific hypothesis and demonstrate a full operational plan for actually running the trial. That includes project management and governance (how decisions are made, how issues are escalated, how data quality is ensured), participant recruitment and retention strategies (how eligible participants will be identified and enrolled, how the study will minimize dropout), well-defined performance milestones, and clear plans for trial conduct from start to finish. Applicants are also expected to plan for dissemination of results, which typically means timely reporting, publication plans, and appropriate sharing of findings so the broader field benefits even if results are negative or mixed.

Regulatory readiness is treated as non-negotiable. If the intervention requires FDA oversight, awardees must obtain an Investigational New Drug (IND) authorization or an Investigational Device Exemption (IDE) approval before the time of award (as applicable) in order to administer the product to humans. This effectively forces applicants to design their development pathway with FDA requirements in mind from the beginning, including chemistry, manufacturing, and controls (CMC) for cell products, release criteria, sterility and potency considerations, and safety monitoring and stopping rules that match the anticipated risks of the specific adult stem cell approach being tested.

The FOA also includes a notable expectation tied to scientific transparency and independent evaluation. Successful applicants proposing adult stem cells as the clinical intervention will be asked to make representative samples of both the source stem cell material and the clinical-grade stem cell-derived product available for in-depth and independent analyses. The intent is to strengthen confidence in product identity, quality, and reproducibility, and to help the broader regulatory and scientific community better understand how product attributes relate to clinical performance and safety.

Eligibility is broad across U.S.-based organizations and includes many types of government entities (state, county, city/township, special districts), public and private institutions of higher education, independent school districts, federally recognized tribal governments and other tribal organizations, public housing authorities/Indian housing authorities, and a wide range of nonprofit and for-profit entities (including small businesses, and for-profits other than small businesses). The FOA explicitly includes additional categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based and community-based organizations and eligible federal agencies. At the same time, it clearly restricts foreign involvement: non-domestic (non-U.S.) entities are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components (as NIH defines them) are not allowed.

From an administrative standpoint, the opportunity is listed as a discretionary program using the cooperative agreement funding instrument, with activity in health-related areas (CFDA numbers include 93.121, 93.350, 93.837, 93.846, 93.847, 93.853, 93.855, 93.866, 93.867). The sponsor agency is NIH, the FOA was created on 2021-07-13, and the original closing date was 2021-10-08. Overall, the program is aimed at teams that can demonstrate a realistic path from a well-developed adult stem cell product to a well-run, milestone-accountable clinical trial that produces rigorous evidence and advances the safety and effectiveness of regenerative medicine.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Regenerative Medicine Innovation Project (RMIP) Investigator-Initiated Clinical Trials (UG3/UH3 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.350, 93.837, 93.846, 93.847, 93.853, 93.855, 93.866, 93.867.
• This funding opportunity was created on 2021-07-13.
• Applicants must submit their applications by 2021-10-08. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA HL 22 014

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