Revision Applications for Regenerative Medicine Innovation Projects (RMIP) (R43/R44)

Purpose

The National Institutes of Health (NIH) and participating NIH Institutes and Centers (ICs) and the U.S. Food and Drug Administration (FDA), through this Funding Opportunity Announcement (FOA), invite revision applications from investigators with active R43/R44 Small Business Innovation Research Grants (SBIR) awards that will support clinical research studies aimed at furthering the field of regenerative medicine (RM) using adult stem cells. 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. These revision applications are expected to focus on innovative projects that propose solutions to widely recognized issues in the development of safe and effective regenerative medicine therapies. Emphasis will be given to projects that address critical issues in product development relevant for regulatory submissions. 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.

Toward these ends, the NIH will consider applications for clinical research involving adult stem cells in the context of generating or supplementing the necessary 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.

This FOA will use the R43/R44 activity codes.  The R43 supports projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). The R44 supports in-depth development of R&D ideas whose feasibility has been established in Phase I and which are likely to result in commercial products or services. 

Background

This FOA, known as the Regenerative Medicine Innovation Project (RMIP), represents one step in fulfilling a new statutory provision set forth in the 21st Century Cures Act. Given the potential of RM to enhance human health and treat disease, Congress included this provision for an Innovation Project in the Act authorizing a total of $30 million, with $2 million available for FY 2017 for the funding of clinical research to further the field of regenerative medicine using adult stem cells, including autologous cells. The Act stipulates that the NIH, in coordination with 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 funds requirement).

Research projects responsive to this FOA are expected to involve both of the following: (1) human subjects or material of human origin, such as cells, tissues, and specimens; and (2) human stem cells that are not of embryonic or fetal origin. Research projects involving induced pluripotent stem (iPS) cells may be supported, as long as the cells used to generate iPS cells were not of fetal or embryonic origin. Applicable research on adult human stem cells may encompass, for example, research on 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). Funds may not be used for research involving human cells of embryonic or fetal origin. 

This FOA 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 subject to the standard NIH review criteria, clinical research projects for this FOA will also be assessed according to the following criteria:

• 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
• Helps 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.

Research Examples

Applications that demonstrate potential to catalyze sustained and accelerated development of the RM field through contributing to the knowledge critical for product development, clinical testing, and data standards and sharing, are strongly encouraged. For example, such projects may:

• Further development of standards and GMP for adult stem cell-based RM products;
• Leverage extant cell production facilities for product preparation and qualification;
• Promote and enhance mechanisms for data standardization, curation, integration, and sharing;
• Utilize clinical trial network(s) to leverage infrastructure and facilitate subject recruitment and follow up as well as data sharing; and/or
• Contribute to a better and shared understanding of current technical and operational barriers as well as the regulatory science issues.

Matching Requirement

An application funded under this announcement is mandated to have at least a 1:1 recipient cost matching for this program, as required by the 21st Century Cures Act. Consideration will be given to any non-federal funds, to include state and local funding (not originating from authorized Federal funds), as well as private-sector investments, in-kind contributions, and donations from foundations provided in support of the application as qualifying for the cost matching ratio requirement. See 45 CFR 75.306 for additional details. The applicant will be required to demonstrate that funds and in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. See additional details and instructions in Section IV.2 and Section VI.3.

Applications that will not be reviewed

The following will not be supported under this FOA:

• Any research using human embryonic or fetal stem cells. Such projects are non-responsive.
• Applications that do not identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. Such applications are incomplete.

This FOA is soliciting for revision applications to R43/R44 Small Business Innovation Research Grant (SBIR) awardees whereas the Companion FOAs solicit support for revision applications to awardees funded by other activity.

For more information please refer to specific Questions and Answers sites for the FOAs: https://www.nih.gov/rmi.   

See Section VIII. Other Information for award authorities and regulations.