Part 1. Overview Information

Key Dates

It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

This Notice of Funding Opportunity (NOFO) invites eligible United States small business concerns (SBCs) to submit Small Business Technology Transfer (STTR) Phase I, Phase II, and Fast-Track grant applications. The funding opportunity will utilize a UT1/UT2 cooperative agreement to support small business concerns (SBCs) to propose applications to create bench top, portable, automated, self-contained systems that maintain 3D tissue constructs (e.g., precise thermal control, fluid pumping and sampling) and provide biologically relevant outputs of tissue health and function. The companion Small Business Innovation Research (SBIR) NOFO allows for submission of Phase I, Phase II, Fast-Track, and Direct to Phase II grant applications.

NCATS has consistently shown leadership in the development of tissue chip technology, in the demonstration of its utility in drug development for safety, efficacy and precision medicine, and in the dissemination of the technology (https://ncats.nih.gov/tissuechip/about). FDA Modernization Act 2.0 declared that the FDA no longer requires animal tests before drug trials in humans, which stimulated increased interest in in vitro New Approach Methods (NAMs) that are more predictive of human response in the safety and efficacy assessment of leading therapeutics. Tissue/organs on chips systems are considered as one of the NAMs. However, the widespread dissemination of tissue chip technology is hindered by the relatively large and complex instrumentation system needed to support the function of the chips, low throughput and specialized expertise needed to operate the systems. The instrumentation typically requires a multidisciplinary team of biomedical engineers and microfluidics experts to assure smooth operations, and biologists to acquire and analyze the data. This underscores the need for improvements in design towards systems capable of real-time, repeated measurements, with ease of manufacturability, and broader user-friendliness.

Through partnerships between NCATS, NASA and the Center for Advancement of Science in Space, the Tissue Chips in Space program has enabled advances in the study of microgravity-associated age?related conditions and has made key technological improvements in the tissue chips instrumentation systems towards automation and miniaturization required for space flight. This Miniaturization and Automation of Tissue Chip Systems (MATCHs) NOFO seeks to translate the lessons learned from the Tissue Chips in Space program in engineering tissue chip platforms towards a smaller footprint and the simplification of systems for ease of use. Previously, NASA has partnered with NIH, BARDA and FDA to develop extended longevity tissue chips (cell culture life up to 6 months) with a focus on the development of systems requiring minimal human intervention. Working with spaceflight payload implementation partners, NCATS-supported tissue chip investigators have developed compact, robust, and reliable platforms which integrate basic support systems (incubation, refrigeration, thermal control, fluid reservoirs, microfluidic pumping systems etc.) as well as technologies to monitor cell health and function (pH, gas concentrations, repeated fluid sampling, microscopy, electrophysiology etc.). This Miniaturization and Automation of Tissue Chip Systems (MATCHs) NOFO seeks to engineer tissue chip platforms towards a smaller footprint and the simplification of systems for ease of use that will result in ease of use and broader accessibility of tissue chips in drug discovery and biomedical research.

Objectives

This NOFO seeks to fund technology development research efforts in instrumentation innovation and approaches for automation and miniaturization of MPS. The technology development proposed should have the potential to significantly propel the field of MPS forward and have the potential to have a large impact on the future analysis of safety and efficacy assessment of therapeutics. A main objective for this funding opportunity would be to create a bench top, portable, easy-to-use, automated MPS with integrated in-line sensors, flow generator with system control and data processing software to provide rapid and reproducible high-throughput analysis. The project could integrate manual methods into an automated system to develop a standalone module. Improved tissue chips instrumentation systems should demonstrate automation capabilities in maintaining culture without external intervention and can be monitored remotely through real-time biosensing and readout capabilities, including telemetry operations. Automation may include automation of tissue preculture and loading, system operation, perfusion systems with or without pumps, automation of cell culture conditions, monitoring and sensing, include in-line sensors, e.g., pressure, pH and oxygen sensors. This self-contained system should maintain 3D tissue constructs (via precise thermal control, fluid pumping and sampling) for extended periods of time and provide biologically relevant outputs of tissue health and function (e.g., by means of fluid sampling, electrode incorporation, microscopy, biosensors). If automated chip exchange is proposed, the system should have proper optical, mechanical, and electrical couplings. The fabrication procedure must be cost effective, mass producible, and robust. The application may include development of a software for instrument control, data acquisition and real-time detection, fast data processing and analysis for high throughput measurements.

Performance metrics of an integrated system for a multi-day protocol should be developed once standard protocols are established and instrument performance is assessed. Once optimal assay parameters are identified, and optimized chips created and integrated for use in the fully automated system with alignment features ensuring proper connection of the fluidic path to the chip, the performance of the system should be characterized and validated. An automated system may be validated by demonstrating compatibility with developed chips and organ-on a chip model and by pre-market end-user testing.

The NOFO deliberately does not specify cost, quality, scale, sensitivity, dynamic range, throughput, or other key metrics since achievable endpoints are likely to substantially differ from one technology to another. However, the applicant must propose quantitative metrics so progress can be evaluated and present convincing rationale that the proposed technology has the potential to scale long-term and to achieve a throughput compatible with widespread adoption by the biomedical and clinical research community. It is expected that applicants will develop and detail scientific and practical definitions of optimal throughput, cost, accuracy, sensitivity, dynamic range, and scale. The long-term goal is to achieve technological advances that enable generation of data at sufficient scale, speed, cost and accuracy to use routinely in safety and efficacy assessment of therapeutics. MATChS is expected to accelerate commercialization and catalyze the widespread use of tissue chips through automation and miniaturization of the instrumentation systems and will lead to the general utility of tissue chips in drug development and regulatory decision-making, as well as in biomedical research in general as a major research tool.

The STTR U1/U2 cooperative agreement mechanism is milestone-driven and involves significant input from NIH program staff regarding project and milestone planning, monitoring of research progress, and go/no-go decision-making. Applicants are encouraged to contact staff at NCATS per Agency Contacts below to ensure that their study design and objectives are in line with the goals of the NOFO. Award recipients will be expected to work with NCATS staff post-award.

Examples of responsive activities and corresponding STTR Phase assignment includes but is not limited to the following technological developments:

STTR Phase I (UT1)

• Development of components of the system
• Development of real-time biosensing
• Development of automated readout capabilities
• Telemetry operations
• Automation of tissue preculture and loading
• Automation of system operation
• Development of perfusion systems
• Development of automation to maintain 3D tissue

STTR Phase II (UT2)

• Integration of the system
• Development of a stand-alone instrument prototype
• Militarization of the system
• Development of software for instrument control and data processing software
• Standard protocols
• Assessment of instrument performance
• System characterization and validation
• Pre-market end-user testing

UT2 Phase I/II Transition

Applicants can submit separate Phase 1 (UT1) or Phase II (UT2) applications. However, if Phase I and Phase II are submitted together in one application (UT2 Fast-Track), then an administrative review will be conducted by NCATS Program staff to decide whether a project will be considered for transition from the Phase I to Phase II. Phase II eligible projects must successfully accomplish milestones of Phase 1 as defined in Milestones Plan. Funding for the Phase II application will be contingent upon (1) assessment of the Phase I progress report and determination that the Phase I goals and milestones were achieved; (2) an update (as necessary) of the Commercialization Plan; (3) determination of the project's potential for meeting the mission of the awarding component and for commercial success; (4) review and approval of other documents necessary for continuation; and (5) availability of funds. The continuation application package is due 2 months prior to the anticipated start date of Phase II.

Applications Not Responsive to this NOFO

Applications not proposing to develop automation and miniaturization of MPS and focused solely on development of healthy and diseased MPS are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding.

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

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;
2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;

1. SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR
2. SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund, or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR
3. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees.

If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner.

If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner.

Definitions:

• Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
• Private equity firm has the meaning given the term private equity fund in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Venture capital operating company means an entity described in 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• ANC means Alaska Native Corporation.
• NHO means Native Hawaiian Organization.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the NIH STTR program.

Performance Benchmark Requirements

Phase I to Phase II Transition Rate Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022.The benchmark establishes a minimum number of Phase II awards the company must have received relative to a given number of Phase I awards received during the 5-fiscal year time period. The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently completed year. The Transition Rate requirement, agreed upon and established by all 11 SBIR agencies, was published for public comment in a Federal Register Notice on October 16, 2012 (77 FR 63410) and amended on May 23, 2013 (78 FR 30951).

For SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years (excluding the most recently-completed fiscal year): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0.25 will not be eligible to apply for a Phase I, Fast-Track, or Direct Phase II (if available) award for a period of one year from the date of the application submission. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the prior 5-fiscal year period.

For application deadlines that fall on or after April 5, 2023: For SBIR and STTR Phase I applicants that have received more than 50 Phase I awards over the past 5 fiscal years (excluding the most recently-completed fiscal year): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0.5 will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase I awards over the 5-fiscal year period.

On June 1 of each year, SBA will identify the companies that fail to meet minimum performance requirements. SBA calculates individual company Phase I to Phase II Transition Rates using SBIR and STTR award information across all federal agencies will notify companies and the relevant officials at the participating agencies. More information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Phase II to Commercialization Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Programs are implementing the Phase II to Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537), with a reopening of the comment period published on September 26, 2013 (78 FR 59410).

For companies that have received more than 15 Phase II awards from all agencies over the past 10 fiscal years (excluding the two most recently completed fiscal year): Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards during the past 10- fiscal year period. Applicants that fail this benchmark will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

For application deadlines that fall on or after April 5, 2023: For companies that have received more than 50 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $250,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

For application deadlines that fall on or after April 5, 2023: For companies that have received more than 100 Phase II awards from all agencies over the past 10-fiscalyears (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $450,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 100 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• SBA Company Registry See How to Apply Application Guide for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a UEI to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

For the STTR program, the PD(s)/PI(s) may be employed with the SBC or the single, partnering non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual.

Each PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration.

The How to Apply Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the How to Apply Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

For STTR:
In Phase I and Phase II, at least 40% of the research or analytical effort must be performed by the small business concern and at least 30% of the research or analytical effort must be performed by the single, partnering research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct, F&A/indirect costs, and fee attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of the SF424 (R&R) application forms.

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of SF424 (R&R) application forms.

Additional details are contained in the SF424 (R&R) SBIR/STTR Application Guide.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:
NCATS Letters of Intent
301-827-9549
ncatslettersofintent@mail.nih.gov

All page limitations described in the How to Apply Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply Application Guide and should be used for preparing an application to this NOFO.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed with the following additional instructions:

Other Attachments:

Milestone Plan: The filename "Milestone Plan.pdf" should be used.

The applicant is required to provide detailed information and timelines for completing all proposed activities according to the specific aims. Applicants must include specific quantitative milestones that will need to be met in order to accomplish the work. Milestones that reflect progress in each specific aim should be easily measurable and realistic. Include specific go/no-go criteria upon which project progress will be assessed for continued funding. Provide a graphical display summarizing the milestones plan in the form of a Gantt Chart.

The Milestone Plan attachment is limited to 1-page maximum. Applications lacking a Milestone Plan attachment will not be reviewed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

Funds to support travel by the PD(s)/PI(s) to the semi-annual NIH Tissue Chip Consortium meeting in Bethesda, Maryland should be requested in the budget.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

SBIR/STTR Information Form

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

Research Strategy: In addition to standard content of Research Strategy, the applicants must address the Milestones. Applicants should propose milestones and timelines to be achieved during the proposed project period toward accomplishing the stated aims of the project. Milestones proposed should be specific and quantitative, and with a clear go/no-go criteria. Milestones will be subject to further negotiations and refinement post review and prior to award. Any additional changes to the milestones post award will be in consultation and negotiation with NCATS staff.

Resource Sharing Plans:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Other Plan(s)

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) applicants are required to address a Data Management and Sharing Plan, regardless of the amount of direct costs requested for any one year. However, SBIR and STTR recipients may retain the rights to data generated during the performance of an SBIR or STTR award for up to 20 years after the award date, per the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Program Policy Directive. An acceptable Data Management and Sharing plan can reference and incorporate these data rights. Further information about SBIR and STTR data rights are enumerated in the NIH GPS.

Appendix:

Note that Phase I SBIR/STTR Appendix materials are not permitted. Only limited items are allowed in the Appendix of other small business applications. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide Instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and time. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the the How to Apply Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at ncatsreferral@mail.nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project and proposed product or service address an important problem, a critical barrier to progress, or unmet need in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims and commercialization of the resulting product or service change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization? How strong is the described market opportunity in the Commercialization Plan including: (i) the product or service being developed; (ii) target customers; and (iii) how the product will solve a demonstrated customer need?

Specific to this NOFO: To what extent will the proposed technological advances lead to automation and miniaturization of MPS system instrumentation and monitoring and propel the field of MPS forward? To what extent will the proposed automated tissue chip platforms have an impact in drug development and as a major research tool in biomedical research laboratories?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project and will they devote sufficient effort to successfully complete the proposed aims? Do the PD(s)/PI(s) have appropriate experience and training to lead this project? If so, have they demonstrated an ongoing record of accomplishments in their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? For projects in later stages, does the team have expertise to commercialize the technology/service/product?

Innovation

Does the proposed product or service represent an innovative approach to addressing an important problem, barrier to progress, or unmet need in research or clinical practice? Does the end product or service proposed in application challenge and seek to shift current research or clinical practice paradigms? Will the end product or service proposed have significant advantages over existing approaches or methodologies, instrumentation, or interventions or those in development?

In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the small business present a reasonable plan to create a temporal barrier against other companies aiming to provide a similar solution, including protecting the intellectual property relevant to the product and technology(ies) being studied or used during the project?

Specific to this NOFO: How well do proposed plans to develop novel technology address making MPS more widely accessible?

Approach

Are the research aims appropriate for the current stage of development? Do the aims represent the necessary steps to further advance the development of the product or service? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? For a Phase I application, are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

For a Phase I, will the strategy establish feasibility, and will particularly risky aspects be managed? Are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

For a Fast-Track, are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Will successful completion of the research aims significantly advance development of the proposed product or service toward eventual commercialization?

For a Phase II, will successful completion of the research aims significantly advance development of the proposed product or service toward eventual commercialization? How well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Specific to this NOFO: To what extent will the approach enable development of a miniaturized MPS system? To what extent are efforts made to ensure the developed platforms will be robust and reliable? Describe the extent to which the approach will lead to automation capabilities for maintaining culture without external intervention. To what extent are appropriate milestones proposed in the Milestone Plan to ensure the proposed work can be accomplished?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific and business environment in which the work will be done contribute to the probability of success and eventual commercialization? Are the small business support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangement?

For a Phase I, does the company have appropriate business expertise and resources, or have they identified appropriate business resources, to accomplish the aims of this project and support commercialization of the proposed product or service?

For a Phase II or Fast-Track, does the applicant have access to the business experts and resources needed to accomplish the aims of this project and to commercialize the proposed product or service?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Phase II Applications

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I (or Phase I-like) objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Phase I/Phase II Fast-Track Applications

For Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

1. To what extent does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

Commercialization (Phase II and Fast-Track Only)

For Phase II and Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

How well does the applicant present the market opportunity, including market segments, that its product or technology will address? Does the applicant understand the barriers to commercialization of its product or service (e.g., regulatory approval, insurance reimbursement, competitive products, customer preferences)? Does the applicant have appropriate strategies to address these barriers?

Does the applicant provide appropriate post-SBIR product development and commercialization milestones and explain how it will achieve these milestones? Does the applicant present a plan for funding the development and commercialization of the product or service? If applicable, did the applicant obtain letters of interest or commitment for such funding and/or resources?

Are the small business executives, management team, and business experts well suited to advance the development and commercialization of the proposed product or service? If not, is there a plan in place to add the necessary expertise as the product advances towards commercialization?

Is there a sound strategy for driving product adoption and generating revenue from the product or service (e.g., product sales, licensing, partnerships)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Phase IIB Competing Renewals

Not Applicable

Revisions

Not Applicable.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications with Foreign Components

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the NCATS Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Security risk as assessed by the HHS Due Diligence Program.

Disclosure Requirements Regarding Ties to Foreign Countries

Upon request applicants are required to disclose all funded and unfunded relationships with foreign countries, using the Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form (referred to as the Disclosure Form hereafter), for all owners and covered individuals. A covered individual is defined as all senior key personnel identified by the SBC in the application (i.e., individuals who contribute to the scientific development or execution of a project in a substantive, measurable way).

Upon request, applicants must submit the completed Disclosure Form and any additional agency-specific information electronically in eRA Commons via the Just-In-Time (JIT) process as described in the NIH Grants Policy Statement (GPS) Section 2.5.1 Just-in-Time Procedures. Applicants must continue to comply with NIH Other Support disclosure requirements as provided in NIH GPS Section 2.5.1 and may be required to provide similar information on the Disclosure Form for covered individuals identified in the application. If participating in this NOFO, SBC applicants applying to CDC and FDA will follow each agency’s policies for submitting additional documents during the pre-award process. Applicants that do not submit the completed Disclosure Form during the JIT process will be deemed noncompliant and not be considered for funding.

Denial of Awards

Applicants are encouraged to consider whether their entity’s relationships with foreign countries of concern will pose a security risk. Prior to issuing an award, NIH (and, CDC or, FDA, as applicable) will determine whether the SBC submitting the application:

• has an owner or covered individual that is party to a malign foreign talent recruitment program;
• has a business entity, parent company, or subsidiary located in the People’s Republic of China or another foreign country of concern; or
• has an owner or covered individual that has a foreign affiliation with a research institution located in the People’s Republic of China or another foreign country of concern.

A finding of foreign involvement with countries of concern will not necessarily disqualify an applicant. Final award determinations will be based on the above finding of foreign involvement and whether the applicant’s involvement falls within any of the following risk criteria, per the Act:

• interfere with the capacity for activities supported by NIH, CDC, or FDA to be carried out;
• create duplication with activities supported by NIH, CDC, or FDA;
• present concerns about conflicts of interest;
• were not appropriately disclosed to NIH, CDC, or FDA;
• violate Federal law or terms and conditions of NIH, CDC, or FDA; or
• pose a risk to national security.

Generally, NIH, CDC, and FDA will not provide SBC applicants the opportunity to address any identified security risks prior to award. NIH, CDC, and FDA will not issue an award under the SBIR/STTR program if the covered relationship with a foreign country of concern identified in this guidance is determined to fall under any of the criteria provided.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" (JIT) information from the applicant as described in the NIH Grants Policy Statement. SBIR and STTR applicants under consideration for award will be required to submit the SBA U.S. Small Business Administration (SBA) issued the Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form during the JIT process. Applicants that fail to submit a Disclosure Form will not be considered for funding.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690)) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the award recipients for the project as a whole, although specific tasks and activities may be shared among the award recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Defining the details and goals of the project within the guidelines of this NOFO.

Determining experimental approaches, designing protocols, setting project milestones, and conducting experiments.

Adhering to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity.

Providing progress updates to the NCATS Program Officer and Project Scientist(s) on a schedule to be negotiated prior to award.

Fully participating in the highly collaborative nature of the NIH Tissue Chips program led by NCATS.

Attending semi-annual NIH Tissue Chip Consortium meetings organized by the NIH.

Coordinating, cooperating, and participating with NIH staff in the scientific, technical, and administrative management.

When needed, working with private partners to acquire and maintain needed resources for the projects.

Performing established standardization and benchmarking milestones.

Ensuring that all affiliated staff will maintain the confidentiality of the information developed by the investigations, including, without limitation, informatics tools, protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.

Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the NOFO.

Participating in a cooperative and interactive manner with NIH staff.

Award recipients will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH. NIH understands that some scientific data generated with NIH funds may be proprietary. In particular, under the Small Business Act, Small Business Innovation Research (SBIR)grantees may withhold their data for 20 years after award date, unless NIH obtains permission otherwise. Refer to the following guidance-https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policy/research-covered-under-the-data-management-sharing-policy. However, NIH still expects SBIR applicants to address data sharing in their applications.

Working with the members of TC Consortium to establish agreements that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners, as appropriate; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner as appropriate and consistent with achieving the goals of the program; (5) procedures for reviewing publications, determining authorship, and industry access to publications.

Ensuring that for activities that involve academic and/or industry collaborations within and outside the TC Consortium there are appropriate research collaboration agreements (e.g., CRA, CDA, MTA etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement terms of award as well as any additional applicable NIH policies and procedures.

Ensuring that the research is conducted in accordance with processes and goals as delineated in this NOFO.

Upon completion or termination of the project, ensuring all study materials, tools, databases and procedures developed from the project are broadly available (e.g., putting into the public domain) or made accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research.

Publications

The Principal Investigator will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The Principal Investigator and Project Leaders are requested to submit manuscripts to the NIH Program Officer and Project Scientist(s) within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the Principal Investigator and appropriate Project Leaders and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.

The successful development of automated system may require either substantial investment and support by private sector industries, and/or may involve collaborations with other organizations such as academic, other government agencies, and/or non-profit research institutions not directly involved in the NIH-funded Tissue Chips Program. NIH recognizes that intellectual property rights are likely to play an important role in achieving the goals of this program.

To this end, all award recipients shall understand and acknowledge the following:

The award recipient is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.

Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the recipient any proprietary rights, including intellectual property rights, or any materials needed by the recipient to perform the project.

The recipient is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Communication Plans

The Principal Investigator(s) will be responsible for:

Participating in regular conference calls with NIH staff.

Participating and presenting findings at the semi-annual NIH TC Consortium meetings convened by the NIH.

Coordinating or jointly publishing findings in a timely manner, and as to have the broadest impact.

Making new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

Program Officer

NCATS will designate program staff, including a Program Officer, to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the notice of award. The Program Officer will make the final determination on the negotiated milestones and will also make the final determination on whether the milestones are met.

Project Scientist(s)

Project Scientists are members of the trans-NIH Microphysiological Systems Working Group that will have substantial scientific/programmatic involvement in the technical assistance, advice and coordination of this team; Project Scientist(s) will facilitate and not direct the activities of the team.

Specifically, Project Scientist(s) will be substantially involved in this project as follows:

Coordinate and facilitate the activities of the program, attend and participate in all meetings of the TC Consortium.

Work with members of the trans-NIH Microphysiological Systems Working Group to review the scientific progress and administrative accomplishments of the award recipients, and review the project for compliance with operating policies and procedures, including meeting milestones. Based on this review, the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of progress or failure to adhere to NIH policies. Review of progress may include regular communications between the Principal Investigator and NIH staff, periodic site visits for discussions with research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.

Prepare up-to-date summaries of program accomplishments based on manuscripts provided by the recipient within two weeks of acceptance for publication.

Participate (with the other trans-NIH Microphysiological Systems Working Group members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted.

Serve as a liaison between the award recipients, the Advisory Councils for those Institutes that plan to administer elements of the NIH Tissue Chips program, and the larger scientific community.

Coordinate the efforts of the recipient with others engaged in MPS research, including other recipients under this NOFO and those recipients involved in related NIH programs.

Attend all trans-NIH Microphysiological Systems Working Group meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.

Periodically report progress to the Directors of NIH Institutes/Centers/Offices involved in the NIH Tissue Chip program.

Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the recipient institutions who are to serve as External Scientific Consultants, as needed.

Maintain public-private partnerships established under the NIH Tissue Chip program.

Provide input into the design of research activities and play a key role in coordinating research efforts.

Monitor milestone progress and help identify recourses if needed.

Ensure that the awarded project(s) adhere to cooperative agreement data-sharing and other resource-sharing policies.

Facilitate collaborations with and access to other NIH-supported research resources and services.

Facilitate negotiations with companies interested in working with the award recipients.

Provide advice on project management and technical performance.

Coordinate and manage trans-NIH Microphysiological Systems Working Group efforts.

Provide guidance to the recipients on private-public partnerships and regulatory agency policies.

Invite experts with relevant scientific expertise to provide feedback on TC program activities.

The NIH reserves the right to curtail or phase out the award in the event of (1) a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) failure to meet procedures and milestones, and/or (3) substantive changes in the management of award(s) that are not in keeping with the objectives of the NOFO.

Areas of Joint Responsibility include:

Collectively, award recipient(s) and the Project Scientist(s) will determine criteria and processes for quality control of information and data to be posted for the research community, consistent with NIH policies and achieving the goals of the program as described in this Notice of Funding Opportunity.

Participate in recurring meetings to discuss progress, obstacles and any other TC-related issues and/or activities.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

• Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. SBIR and STTR recipients may retain the rights to data generated during the performance of an SBIR or STTR award for up to 20 years after the award date, per the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Program Policy Directive. An acceptable Data Management and Sharing plan can reference and incorporate these data rights. Further information about SBIR and STTR data rights are enumerated in the NIH GPS.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

NIH requires that SBIR/STTR recipients submit the following reports within 120 days of the end of the grant budget period unless the recipient is under an extension.

• Final RPPR (requirements have recently changed - please see the NOT-OD-17-085)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR)
• SBIR.gov
• Quarterly reports are due to the Payment Management System 30 days following the end of each calendar quarter.

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Disclosure of Foreign Relationships Reporting Requirements

Recipients are responsible for monitoring their relationships with foreign countries of concern post-award, for any changes that may impact previous disclosures. SBCs receiving an award under the SBIR/STTR program are required to submit an updated Disclosure Form to report any of the following changes to NIH (and, CDC or, FDA, as applicable) throughout the duration of the award:

• any change to a disclosure on the Disclosure Form;
• any material misstatement that poses a risk to national security; and
• any change of ownership, change to entity structure, or other substantial change in circumstances of the SBC that NIH, CDC, and FDA determine poses a risk to national security.

Regular, annual updates are required at the time of all SBIR/STTR annual, interim, and final Research Performance Progress Reports (RPPRs). For changes that occur between RPPR submissions, updated Disclosure Forms are required within 30 days of any change in ownership, entity structure, covered individual, or other substantive changes in circumstance, as described above. Recipients are required to upload these updated disclosures using the Additional Materials (AM) tool in eRA Commons.

If the recipient reports a covered foreign relationship that meets any of the risk criteria prohibiting funding described in this NOFO, NIH, CDC, and FDA may deem it necessary to terminate the award for material failure to comply with the federal statutes, regulations, or terms and conditions of the federal award. Refer to NIH GPS Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support for more information. Recipients are encouraged to monitor their covered foreign relationships post-award and avoid entering into relationships, both funded and unfunded, that may pose a security risk and jeopardize their ability to retain their award.

Agency Recovery Authority and Repayment of Funds

An SBC will be required to repay all amounts received from NIH, CDC, and FDA under the award if either of the following determinations are made upon assessment of a change to their disclosure:

• the SBC makes a material misstatement that NIH, CDC, and FDA determine poses a risk to national security; or
• there is a change in ownership, change in entity structure, or other substantial change in circumstances of the SBC that NIH, CDC, and FDA determine poses a risk to national security.

The repayment requirements and procedures provided in Section 8.5.4 Recovery of Funds of the NIH GPS apply and may also be subject to additional noncompliance and enforcement actions as described in Section 8.5.2 of the GPS. Recipients are required to follow the repayment procedures provided in the Guidance for Repayment of Grant Funds to the NIH.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)
Website to Email: http://sbir.gov/feedback?type=reg

Dmitriy Krepkiy, Ph.D.
Office of Special Initiatives
National Center for Advancing Translational Sciences, NIH
Phone: 301-451-2232
Email: dmitriy.krepkiy@nih.gov

Marilyn Moore-Hoon, Ph.D
National Center for Advancing Translational Sciences (NCATS)
Phone: 301-594-4861
Email: marilyn.moorehoon@nih.gov

Imoni Washington, J.D.
National Center for Advancing Translational Sciences, NIH
Telephone: 301-435-2939
Email: imoni.washington@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 45 CFR Part 75 and 2 CFR Part 200.

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, P.L. 115-232, and P.L. 117-183. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

The STTR Program is mandated by the Small Business Reauthorization Act of 1997 (P.L. 105-135), and reauthorizing legislation, P.L. 107-50, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, P.L. 115-232, and P.L. 117-183. The basic design of the NIH STTR Program is in accordance with the Small Business Administration (SBA)STTR Policy Directive.