Memorandum of Understanding
between the National Institutes of Health
and Center for Biologics Evaluation and Research
U.S. Food and Drug Administration regarding coordination
of and participation in the
21st Century Cures Regenerative Medicine Innovation Project
This MOU is for the implementation of Section 1001(b)(4)(D) of the 21st Century Cures Act1 (the Act). Given the potential of regenerative medicine (RM) to enhance human health and treat disease, the Act authorized funding to the NIH for the Regenerative Medicine Innovation Project (RMIP), which supports clinical research to further the field of RM using adult stem cells, including autologous cells, in the total amount of $30 million for FY 2017 through FY 2020, with $2 million authorized for FY 2017. The Act stipulates that the NIH, in coordination with the U.S. Food and Drug Administration (FDA), award funds contingent upon the recipient making available non-Federal contributions in an amount not less than $1 for each $1 of Federal funds provided in the award (i.e., a matching requirement).
Implementation of the RMIP
To utilize the FY17 RMIP funds, participating NIH Institutes and Centers (ICs), in coordination with the Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration (FDA), intend to publish twelve Funding Opportunity Announcements (FOAs) for competitive revisions2, consistent with the applicable legal and policy framework, that will support clinical research studies aimed at furthering the field of RM using adult stem cells.
The planned awards will be subject to the legal and policy obligations summarized in the NIH Grants Policy Statement and as otherwise specified in the Notice(s) of Award, and will support revision projects that utilize rigorous science and reproducible methods to establish proof of concept and a robust evidence base for clinical development. To advance the field of RM more broadly, applicants will be asked to propose solutions to widely recognized issues in the development of safe and effective RM interventions.
Areas of focus may include:
• Development of platforms and technologies to address critical issues in product development relevant for regulatory submissions, including areas such as tools, methods, standards, or applied science that support a better understanding and improved evaluation of product manufacturing, quality, safety, or effectiveness
• Evidence for clinical development, including but not limited to the submission of a pre-Investigational New Drug (IND) or pre-Investigational New Device Exemption (IDE) package; the
submission of an IND/IDE application; or to support such research conducted under an authorized IND or IDE
• Biologics (e.g., growth factors, cytokines) and biomaterials (e.g., ECM, scaffolds) that stimulate host adult stem cell growth, differentiation, and function or otherwise directly act upon adult stems cells to support innate host healing mechanisms, treat disease, and/or restore function. Funding could be used, for example, for the appropriate chemistry, manufacturing, and controls development to support the production of such products for clinical trials using good manufacturing practices (GMP)
• Development of standards for adult stem cell-based RM products and standards for development of manufacturing processes and procedures that would comply with GMP
• Mechanisms for data standardization, curation, integration, and sharing
• Subject recruitment and follow-up as well as data sharing
• Technical and operational issues, including regulatory science issues
The FOAs will utilize multiple activity codes3. The estimated timeline is:
• NOITPs published: March 31, 2017 (completed)
• FOAs published: May 2017
• Receipt date: June 2017
• Ad hoc Council date: September 2017
The awards will support highly meritorious clinical research projects proposing to explore and enable the development of safe and effective RM interventions. Specifically, for FY 2017 funds, in addition to being reviewed under the standard NIH review criteria, clinical research projects will also be assessed according to the following specific criteria, consistent with the NIH peer review standards at 42 CFR 52h.8, as well as funding priorities and procedural and programmatic considerations:
• Contributes to breadth/diversity of RM science;
• Addresses critical issues relevant to clinical research and regulatory submissions including those related to product development. Areas of focus may include improved tools, methods, standards, or applied science that support a better understanding and improved evaluation of product manufacturing, quality, safety, or effectiveness; and
• Will help to significantly build or advance the field of RM by contributing to foundational knowledge while addressing a well-recognized challenge in clinical development including the development and evaluation of safe and effective RM products.
For the RMIP awards, NIH will require at least a 1:1 recipient cost matching for this program, as required by the 21st Century Cures Act. NIH will consider any non-federal funds, to include state and local funding (not originating from Federal funds), as well as private-sector investment and donations from foundations provided in support of the application as qualifying for the cost matching ratio requirement. Such matching requirements will be carried out consistent with applicable regulations and policy.
NIH Roles and Responsibilities
The NIH Director has designated the Director of the National Heart, Lung, and Blood Institute to coordinate and manage the RMIP on his behalf. Final decisions about key RMIP issues, including awarding of specific grants, will be made by the NIH Director.
Participating NIH ICs have designated representatives to two committees that are key components of the governance structure for the RMIP: the RM SME Working Group and the RMIP Senior Oversight Committee. These two groups advise on issues pertaining to implementation of the RMIP, including the approach to solicitation and review of applications for RMIP funding.
Review of applications received in response to the RMIP FOAs will be carried out by Special Emphasis Panels (SEPs) established by NIH consistent with the NIH peer review process under 42 CFR 52h with input from the participating NIH ICs. Participating ICs may be tasked with identifying areas of expertise and potential reviewers for the SEPs, and with contacting potential reviewers. In some cases, IC personnel may be asked to participate as reviewers on the SEPs.
Secondary/Council review of the applications will be carried out by an Advisory Council identified by the NIH Office of the Director. Participating ICs will not be providing funding for the research projects awarded through the RMIP FOAs; such funds will come from the NIH Innovation Account established by the 21st Century Cures Act. However, relevant ICs, i.e., those whose current grantees are selected for a competing revision award, will have responsibility for administering the parent grant and the competing revision award related to the RMIP.”
Communications: The participating ICs will work jointly on the solicitation and peer review process and administration, advise on matters related to the management of the FOAs, and communicate with the scientific community concerning the RMIP.
FDA Roles and Responsibilities
CBER staff will participate in discussions with NIH about implementation of the RMIP and provide input on the state of RM science, including the current knowledge gaps and technical, scientific, and operational challenges, especially with respect to regulatory science needs.
As permitted under law, regulation, or policy, CBER staff will have access to the applications that are received in response to the FOAs and may participate as observers on the SEPs to hear the full range of issues and discussion. CBER staff will likely not serve as reviewers on the SEPs.
CBER staff will provide feedback on whether an IND or IDE application is required for projects being considered for funding when an applicant has asserted that the project does not require an IND or IDE application.
CBER staff will participate with NIH in the conceptualization, planning, and execution of future RMIP activities, such as workshops and the development of an RM blueprint to guide the RMIP in FY18-20.
CBER will not be providing funding for the research projects funded by the RMIP FOAs, and will not have responsibility for administering grants, contracts, or supplements related to the RMIP.
1/21st Century Cures Act, Public Law No. 114-255
2/A competing revision is a request for an increase in support in a current budget period for expansion of the project's approved scope or research protocol. Applicants must apply and undergo peer review.
3/Activity codes listed in the NOITP: SBIR (R43/R44), STTR (R41/R42), U01, U54, UM1, UC4, U24, R01, R24, UM2, and P50
Period of Performance
April 10, 2017 - August 31, 2021. (This will cover the post-award timeframe.)
Concurrence with Release
CBER/FDA acknowledges the above roles and responsibilities and concurs with the release of the RMIP FOAs to the NIH GPS System for publication in the NIH Guide.
APPROVAL AND ACCEPTANCE:
For the U.S. Food and Drug Administration
Peter Marks, M.D., Ph.D., Director
Center for Biologics Evaluation and Research
For the National Heart, Lung, and Blood Institute
Gary H. Gibbons, Director
National Heart, Lung, and Blood Institute