Background The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, also known as America's Seed Fund, are one of the largest sources of early-stage capital for technology commercialization in the United States. These programs enable US-owned and operated small businesses to conduct research and development that has a strong potential for commercialization. National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) support small businesses through the SBIR and STTR programs to translate promising technologies and products to the private sector that align with their mission to improve health and save lives. The SBIR program, as established by law and reauthorized under Public Law 114-328, Section 1834 and Public Law 115-232, is intended to meet the following goals: stimulate technological innovation in the private sector; strengthen the role of small business in meeting federal research and development needs; increase the private sector commercialization of innovations developed through federal research and development funding; foster and encourage participation in innovation and entrepreneurship by women and socially or economically disadvantaged persons. In addition, the STTR program aims to foster technology transfer through cooperative research and development between small businesses and research institutions. Federal agencies with extramural research budgets over $100 million are required to set-aside 3.2% of their budget to SBIR, and those with research budgets over $1 billion are required to set aside 0.45% of funds for STTR. The SBIR/STTR program is a phased program. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. An objective of the SBIR and STTR programs is to increase private sector commercialization of innovations derived from federally supported research and development. At the conclusion of an SBIR/STTR Phase II, it is expected that the small business will fully commercialize their product or technology using non-SBIR/STTR funds (either federal or non-federal). Purpose This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) invites eligible United States small business concerns (SBCs) to submit Small Business Innovation Research (SBIR) Phase I, Phase II, Direct to Phase II (NIH Only), Fast-Track (NIH only), and Phase IIB (NIH only) grant applications. Small business applicants interested in submitting an STTR grant application should submit to PA-20-261 or PA-20-265. NIH Fast-Track: An NIH SBIR Fast-Track incorporates a submission and review process in which both Phase I and Phase II applications are submitted and reviewed together as one application to reduce or eliminate the funding gap between phases. NIH Direct to Phase II: For small businesses that have already demonstrated scientific and technical merit and feasibility but have not received a Phase I SBIR or STTR for that project, NIH can issue a Direct to Phase II award. The NIH Direct to Phase II will accept Phase II submissions regardless of the funding source for the proof of principle work on which the proposed Phase II research is based. Small businesses that are eligible to submit Phase II applications for projects that were supported with a Phase I SBIR or STTR award are expected to submit the regular Phase II application as a "Renewal" application based on the awarded Phase I SBIR or STTR project. Only one Phase II application may be awarded for a specific project supported by a Phase I award. NIH Phase IIB: Some projects initiated with SBIR or STTR funding require considerable financing beyond the SBIR and STTR Phase II to achieve commercialization. NIH Institutes and Centers (ICs) may allow small businesses who have been awarded a Phase II SBIR or STTR to submit a Phase IIB (second, sequential Phase II) SBIR application that will provide additional funding for Phase II SBIR or STTR projects. These renewals are typically offered for those projects that require extraordinary time and effort, including those requiring regulatory approval or developing complex instrumentation, clinical research tools, and behavioral interventions. Commercial potential (i.e. the probability that an application will result in a commercial product) will be a strongly considered in review (refer to Section V. Application Review Information) and making funding decisions. Applicants are encouraged to secure substantial independent third-part investor funds (i.e., third-party funds that equal or exceed the requested NIH funds). An applicant's ability to secure substantial independent third-party investor funds will help validate the commercial potential of the proposed SBIR Phase IIB project. Examples of third-party investors include, but are not limited to, another company, a venture capital firm, an angel investor, a foundation, a university, a research institution, or a State or local government, or any combination of the above. Applicants should provide a commercialization plan that describes the long-term commercialization strategy and details on any independent third-party investor funding that has already been secured or will be provided during the Phase IIB project period. If applicable, the application should include letters of support from third-party investors. NIH ICs that accept Phase IIB applications, either through this SBIR FOA or other specific FOAs, are listed in the PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA. Additional requirements and instructions (e.g., submission of a letter of intent) are available in the specific IC research topics section and in the NIH Targeted Funding Opportunities that allow Phase IIB applications. Specific Objectives The PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA represent scientific program areas that may be of interest to applicant small businesses in the development of projects that have potential for commercialization. Small business concerns that have the research capabilities and technological expertise to contribute to the R&D mission(s) of the NIH, CDC, or FDA awarding components identified in this FOA are encouraged to submit SBIR grant applications in these areas. SBIR grant applications will also be accepted and considered in any area within the mission of the Components of Participating Organizations listed for this FOA. In addition to the general SBIR solicitations, some awarding components have additional, specific NIH Targeted Funding Opportunities of potential interest to small businesses. Applicants are not required to identify a potential awarding component prior to submission of the application but may request one on the Assignment Request Form. Staff within the NIH’s Center for Scientific Review (CSR) office, the single receiving point for all NIH, CDC, and FDA grant applications, will assign all applications to the most appropriate Agency and Institute/Center (IC) based on their mission and the science proposed. For specific information about the mission of each NIH IC, visit the List of NIH Institutes, Centers, and Offices website. All applications submitted to this Parent Funding Opportunity Announcement must propose clinical trial(s). SBIR applications that do not propose clinical trial(s) should be submitted to PA-20-260. Applicants should note that some ICs only accept applications proposing mechanistic studies through this funding opportunity announcement and are noted in the PHS 2020-2 SBIR/STTR Program Descriptions and Research Topics for NIH, CDC, and FDA. A mechanistic study is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. If the proposed research project includes clinical trial other than a mechanistic study that would be assigned to one of these ICs, applicants are advised to contact relevant Scientific/Research staff to discuss alternative mechanisms of support of these studies. Further information about the SBIR and STTR programs can be found at https://sbir.nih.gov/. Frequently asked questions are available to assist applicants and can answer many basic questions about the program.