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Frequently Asked Questions
Click on a category name below to display a list of questions. Can't find an answer to your question? Contact us at RMIP@nih.gov.
Q1. Why was the Regenerative Medicine Innovation Project launched?
Given the tremendous potential of regenerative medicine to enhance human health and treat disease, Congress included a provision in the 21st Century Cures Act — a law passed in December 2016 to accelerate medical discovery and innovation — to support a Regenerative Medicine Innovation Project (RMIP). The RMIP aims to accelerate the field by supporting clinical research on adult stem cells while promoting the highest standards for protecting patient safety during the conduct of research. The RMIP is one of four Innovation Projects authorized under the Act; the others are the Precision Medicine Initiative (“All of Us”), the Beau Biden Cancer Moonshot, and the BRAIN Initiative.
Q2. How much funding is available for the RMIP overall?
The 21st Century Cures Act authorizes $30 million (distributed over fiscal year (FY) 2017 through FY 2020) for the funding of clinical research to further the field of regenerative medicine (RM) using adult stem cells. Specifically, the Act authorizes $2 million in FY 2017, $10 million in each of FY 2018 and FY 2019, and $8 million in FY 2020. The availability of these funds is subject to Congressional appropriation.
To amplify the benefit of these funds, the Cures Act requires recipients to contribute at least an equal amount of non-Federal dollars or in-kind contributions of non-Federal origin.
Available funds/number of awards
Q3. A Funding Opportunity Announcement (FOA) was issued in August 2019 utilizing the UG3/UH3 cooperative agreement funding mechanism. How much money is available for this FOA and what type of research projects are being accepted?
NIH is only accepting applications that propose clinical trials and anticipates committing up to $3.2 million in total federal funds in FY 2020.
Q4. How many RMIP awards does NIH anticipate making under the August 2019 FOA?
NIH anticipates making up to 5 new awards in total for this FOA. Awards are expected to be made in May 2020.
Types of awards
Q5. What funding mechanism will these RMIP awards utilize?
Awards will utilize the following funding mechanism:
- Investigator-Initiated Clinical Trials (UG3/UH3 – Clinical Trial Required)
Q6. The RMIP FOAs issued in FY 2018 accepted preclinical research projects. Are preclinical research projects being accepted in FY 2020?
No. For FY 2020, only clinical trial applications are being solicited for the funding mechanism described above.
Requirement for matching funds
Q7. I understand that there is a matching requirement associated with these awards. What is the requirement, exactly?
As stipulated in the 21st Century Cures Act, RMIP grantees must make non-Federal contributions to their projects in “an amount not less than $1 for each $1 of Federal funds provided in the award.” In other words, grantee contributions must be at least equal in value to the Federal dollars provided under the RMIP award. Applicants must identify the source, type, and amount of contribution(s) proposed to meet the matching requirement and explain how the value of any “in-kind” contributions was determined (see Q10).
Q8. Which of the awarded Federal funds must be matched? Must we match the total award (direct and indirect costs) or just the direct costs awarded?
In keeping with the 21st Century Cures Act, NIH expects award recipients to match the total federally awarded amount (normally direct plus indirect costs, but see also Q11 below).
Q9. What kinds of contributions will satisfy the matching requirement?
Matching contributions may be monetary or “in-kind” (i.e., non-monetary contributions). Matching contributions may not be from Federal sources, however, or paid for with Federal dollars. They may be in the form of funding, or paid for by funds, from non-Federal sources such as private industry, foundations, and institutional funds (not derived from Federal grants or contracts).
Q10. What do you mean by “in-kind contributions”? What are some examples of acceptable in-kind contributions?
“In-kind” contributions are non-monetary contributions. Acceptable forms of in-kind contributions include personnel time and effort, facilities and administrative (i.e., indirect) costs, equipment, and real estate. Importantly, to be eligible, in-kind contributions must not have been obtained with support from any Federal agency.
Q11. What if we intend to forgo all reimbursement for our facilities and administrative (indirect) costs as a form of “in kind” contribution to the proposed RMIP project? Must we match what would have been the total award (direct and indirect costs), or just the direct cost amount actually awarded?
If the institution is forgoing all indirect cost reimbursement, and consequently the NIH award is only for direct costs, then the institution must match the direct cost amount (since the 21st Century Cures Act requires matching all federally awarded dollars).
Q12. May we use revenue generated by research-related activities, such as fees charged to research participants, to fulfill the matching requirement?
No. Such revenue is considered “program income.” Program income is not an allowable source of matching dollars. Program income is gross income earned by a recipient, a consortium participant, or a contractor under a grant that was directly generated by the grant-supported activity or earned as a result of the award. Program income includes, but is not limited to, income from fees for services performed; charges for the use or rental of real property, equipment or supplies acquired under the grant; the sale of commodities or items fabricated under an award; charges for research resources; registration fees for grant-supported conferences, and license fees and royalties on patents and copyrights.
Q13. May matching funds be obtained from a foreign government or entity?
The 21st Century Cures Act only specifies that matching funds must be non-Federal in origin. Other policies, laws and regulations, however, may impose restrictions or requirements for funds originating from a foreign source. Before relying on such sources of money, investigators should first discuss the scenario with the appropriate agency contact listed at the end of the FOA, who can consult in turn with appropriate entities, including legal counsel, about the acceptability of the source and the requirements that may apply.
Q14. When must the matching contributions be available? All at the outset of the project? By the end of the award period? In each year that the awarded funds are drawn?
Matching contributions must be available in each budget period in an amount at least equal to the amount of Federal dollars awarded for that period. Any matching contribution provided in excess of a given budget period’s obligation may be credited toward the following budget period’s matching obligation.
For applications to the UG3/UH3 FOA, there are two budget periods: UG3 (up to one year) and UH3 (up to four years). For applications to all other FOAs, there is a single budget period: the period of the award.
Types of eligible research projects
Q15. How is “regenerative medicine” defined for the purpose of the RMIP and its associated funding opportunities?
An aim of the 21st Century Cures Act is to accelerate the development of regenerative medicine therapies, which the Act describes as including “cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products…” RM research eligible for 21st Century Cures Act funding may encompass, for example, research on biologics (e.g., growth factors, cytokines) and biomaterials (e.g., extracellular matrix, scaffolds) that stimulate or support host adult stem cell growth, proliferation, differentiation, and function or otherwise directly act upon adult stems cells to support innate host healing mechanisms, treat disease, and/or restore function. RM research in this context is interpreted to include gene therapies that lead to a durable modification of adult stem cells.
Q16. Is basic research on stem cells eligible for these funds?
No. Basic research is a critically important component of regenerative medicine research and is funded by other NIH programs. The 21st Century Cures Act requires that the RMIP funds be used “to award grants and contracts for clinical research to further the field of regenerative medicine using adult stem cells, including autologous stem cells” (see Q17 below).
Q17. If only clinical research applications are eligible for funding under the RMIP, how is “clinical research” defined for this purpose?
Per the FOA, proposed projects will be considered clinical research if they involve: (1) human subjects and/or (2) material of human origin, such as cells, tissues, and specimens.
Q18. Is research using cells from previously approved human embryonic stem cell lines eligible for these funds?
No. The 21st Century Cures Act stipulates that these funds are to be used for regenerative medicine research using adult stem cells. For the purpose of research conducted with the RMIP funds, adult stem cells may not be derived from human embryonic or fetal sources.
Q19. May RMIP funds be used to support research with induced pluripotent stem cells (iPSCs)?
Research with human iPSCs is eligible for RMIP funding, provided the stem cells were not derived from embryonic or fetal cells.
Q20. Is research using human neonatal stem cells eligible for these funds?
Yes. Human neonatal stems cells (e.g., cells derived from foreskin) are considered adult stem cells for the purpose of this funding opportunity since they are not derived from fetal or embryonic sources.
Q21. Is research that aims to develop products that stimulate human host stem cell growth and function eligible for these awards?
Yes. Eligible projects encompass, for example, research on biologics (e.g., growth factors, cytokines) and biomaterials (e.g., extracellular matrix, scaffolds) that stimulate or support host (i.e., endogenous) adult stem cell growth, self-renewal, proliferation, differentiation, and function or otherwise directly act upon adult stems cells to support innate host healing mechanisms, treat disease, and/or restore function.
Q22. Is work involving only animal models with animal stem cells eligible for these funds?
No. Research using only animal models would only be eligible if it entailed the testing of adult stem cells of human origin in those models. Research using only animal models and animal stem cells is not eligible because it is not “clinical research” as described in the FOAs.
Q23. To be eligible for the RMIP clinical trial awards, must my project always involve a product that is under an authorized IND application or approved IDE application for administering the product to humans?
Not necessarily. Certain types of clinical trials eligible for RMIP funding may not legally require IND authorization or IDE approval. Furthermore, three of the four award mechanisms being utilized are for research that does not involve a clinical trial (and hence, in those cases, an IND or IDE application is not required); the mechanisms being used for preclinical research are focused on late-stage or IND/IDE enabling research. See also Q26 below.
Q24. If I am proposing a clinical trial requiring IND authorization or IDE approval, when must I obtain it?
IND authorization or IDE approval must be obtained prior to receipt of award, as originally scheduled (i.e., awards will be not delayed to allow extra time to obtain authorization/approval). An applicant who does not obtain necessary authorization/approval prior to the scheduled award date will be ineligible for award.
Q25. I see in the preclinical FOAs (U01, U44, UT2) that there is a requirement for the applicant to have been in dialogue with FDA regarding a future IND or IDE. What type of information do I need to submit in my application to document this?
Applicants should describe their interactions with FDA, including the dates of any pre-IND meetings and other communications.
Q26. I am using an autologous adult stem cell product that I believe is not subject to IND authorization or IDE approval. To submit a responsive application, what is required of me in terms of obtaining confirmation from FDA on this point?
If the protocol is judged by the applicant to not require an IND/IDE, the applicant should provide a written explanation accompanied by documentation from FDA. Applicants are encouraged to consult with FDA early on in the process for an authoritative opinion that their product is exempt from the IND/IDE requirements by submitting a request for designation (RFD) to obtain a formal FDA determination of their cell product (see instructions at https://www.fda.gov/RegulatoryInformation/Guidances/ucm126053.htm). Please note that if the protocol is exempt from the requirement to file an IND or IDE application, RMIP applicants are required to provide to NIH — prior to award — a copy of a formal designation letter from FDA.
Role of FDA
Q27. The Act directs NIH to award funding “…in coordination with FDA.” How will this coordination be achieved?
FDA is an essential partner and collaborator with NIH on the implementation of the RMIP. As such, FDA provides critical input on the state of regenerative medicine science, including the current knowledge gaps and technical, scientific, and operational challenges, especially with respect to regulatory science needs. NIH has worked with FDA on the development of the FOAs, including the design of the review criteria and process. FDA staff may participate as observers on the initial review panels assessing the scientific merits of the applications.
Regenerative Medicine Innovation Catalyst
Q28. What is the Regenerative Medicine Innovation Catalyst (RMIC)?
The RMIC is a resource that is being established and will be funded by NIH to catalyze the efficient development of safe and effective adult stem cell-based therapies and to further the field of regenerative medicine. The RMIC will offer services and resources to RMIP investigators to facilitate the conduct of their studies. Ultimately, the activities of the RMIC will also allow a deeper understanding of stem cell clinical products, in part by facilitating the correlation of cell characterization with clinical outcomes data. Toward these ends, it is anticipated that the RMIC will:
- Conduct in-depth and independent characterization of the source stem cell line and stem cell products being administered to research subjects (see Q30 and Q31)
- Offer support/assistance for development of clinical-grade product
- Offer regulatory support to assist investigators in understanding and addressing FDA regulatory requirements
- Provide storage and dissemination services for in-depth cell characterization results and clinical data
Operational details will be forthcoming regarding how RMIP awardees may avail themselves of the RMIC’s services. Applicants interested in obtaining regulatory support services and/or assistance with cGMP or phase-appropriate product development should consult with the relevant Scientific/Research contact listed in the FOAs as early as possible in the application process, as these services may have budgetary implications.
Q29. What must RMIP awardees provide to the RMIC as a condition of their award?
RMIP awardees will be expected to provide: (1) representative samples of the source stem cell line, (2) representative samples of the clinical-grade stem cell product, and when applicable (3) individual participant-level data emanating from an RMIP-funded clinical trial. Details about timeframes and procedures will be negotiated with individual recipients at the time of award.
Q30. Why am I expected to submit cell samples to the RMIC for characterization, and what types of analyses will be done? Will my intellectual property be protected in the process?
While our understanding of stem cell biology is progressing rapidly, it is nonetheless widely acknowledged that a critical challenge in the development of stem cell therapies is the need for a more complete characterization of the biological attributes of stem cell products. Such in-depth characterization would enable a fuller understanding of how clinical outcomes may be related to particular cell characteristics and may inform future product development and enhance reproducibility of subsequent studies. Towards these ends, RMIP grantees will be asked to submit representative samples from their source cells, as well as the clinical-grade cell products derived from them, to the RMIC for in-depth analysis of cell characteristics. The RMIC will conduct in-depth analyses of cell surface markers, -omics characteristics and other assays as appropriate. NIH recognizes that commercialization is important to developing products that will ultimately be made available to the public, and thus any proprietary information provided will be protected to the extent possible under the law.
Q31. What will be done with the cell characterization results? Will investigators be expected to modify their study protocols in response to these results? Will the assay results be shared broadly?
Investigators will receive the in-depth cell characterization results on the cell samples that they provide. However, the biologic and clinical significance of various cell characteristics for efficacy and safety may not be known for some time, since making that correlation will require additional data, study and analysis. Thus, the primary purpose of conducting the cell characterization studies is to inform future research activities and the field at large. In-depth cell characterization assay results are not intended to inform clinical decisions during the conduct of the clinical trial, nor are they intended to factor into the normative oversight requirements and processes (e.g., FDA, DSMB, IRB) for the source study. Investigators may nonetheless consider what the results indicate relative to their scientific approach and whether any changes are warranted. In general, cell characterization assay results will be made available to the broader research community via the RMIC one year following the end of award (for preclinical studies) or the primary completion date (for clinical trials).
Q32. Will the RMIC share my clinical trial data?
- The deidentified individual participant-level locked dataset will be shared via the RM Innovation Catalyst through controlled access as appropriate in compliance with applicable Federal laws, regulations, and policies according to the following schedule:
- Primary outcome data will be shared one year following the primary completion date.
- The full dataset will be shared two years following the primary completion date.
Q33. What are the regulatory support services being offered by the RMIC?
The RMIC will offer free of charge to all RMIP awardees technical and administrative services to assist them in understanding and addressing regulatory requirements. These include assistance with interpreting regulatory guidance documents during the IND application process and providing consultation regarding optimal preparation for FDA meetings. Such services may be provided through the Production Assistance for Cellular Therapies (PACT). PACT will not carry out required regulatory activities on behalf of the RMIP awardee such as filing an IND or IDE application and associated information or conducting other regulatory representational activities. PACT was established by NHLBI as an NIH-wide resource and has the requisite regulatory expertise to address all aspects of the translational process for the development of cellular therapeutics. Interested applicants should consult early in the application process with the relevant Scientific/Research contact listed in the FOAs to determine the suitability of these services for their product development process.
Q34. What kind of phase-appropriate manufacturing assistance may be provided to RMIP awardees?
RMIC may under certain circumstances provide assistance for the development of clinical-grade product through the Production Assistance for Cellular Therapies (PACT). PACT was established by NHLBI as an NIH-wide resource to provide clinical grade phase-appropriate cell product manufacturing assistance to investigators conducting in vivo and in vitro studies. NIH Institutes and Centers participating in the FOAs will determine the mechanism for support of assistance services in the development of clinical-grade cell product. Applicants are encouraged to consult early in the application process with the relevant Scientific/Research contact listed in the FOA for further information.
Q35. In preparing my application, must I budget for the costs of using the RMIC’s services?
Applicants interested in these services should consult with the appropriate NIH Scientific/Research Contact listed in the FOA as early as possible in the application process to determine the suitability of these services for their cell development process, the mechanism(s) available to fund these product development services, and whether applicants need to budget for them in their application.
Q36. Are non-RMIP awardees eligible for the RMIC services?
Not at this time. Initially, the RMIC will only be available to the RMIP awardees. In the future, the role of the RMIC relative to other regenerative medicine studies may evolve.
Q37. The RMIP FOAs state that cell samples must be submitted to the RMIC for characterization. My project involves a product intended to stimulate the growth of endogenous (i.e., host) stem cells, and does not involve the administration of stem cells per se to a human. Am I subject to this sample submission requirement?
Q38. How will funding decisions on these applications be made?
As with all grant applications submitted to NIH, RMIP applications will undergo two levels of peer review: an initial review of the proposal’s scientific and technical merits, and a second level of review by an advisory council regarding funding and research priorities. Initial peer review of RMIP applications will be conducted by a Special Emphasis Panel. Final funding decisions will be made by NIH leadership.
Q39. Where can I get more information about the RMIP funding opportunity?
Please visit https://www.nih.gov/rmi to find the FOAs, FAQs, and more. If you have questions about this initiative, you may also write to RMIP@nih.gov. Finally, you are strongly encouraged to discuss your application with the appropriate agency contact listed at the end of the FOA; early contact is important for developing a complete application and facilitating review.
This page last reviewed on August 21, 2019