Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

U.S. Food and Drug Administration (FDA)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Botulinum Toxin Potency Assay using Tissue Chips (BoT PATCh) (U43/U44 - Clinical Trail Not Allowed)
Activity Code

U43/U44 Small Business Innovation Research (SBIR) Cooperative Agreements - Phase I Phase II

Announcement Type
New
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-TR-22-032
Companion Funding Opportunity
RFA-TR-22-031 , UT1 Small Business Technology Transfer (STTR) Cooperative Agreements ? Phase I
Assistance Listing Number
93.350, 93.853
Funding Opportunity Purpose

This FOA provides support using the SBIR cooperative agreement mechanisms for the development, regulatory qualification and commercialization of alternative approaches methods (NAMs) that specifically utilizes the neuromuscular junction Tissue Chips (TC) platforms that will replace the LD50 assay (mouse lethality bioassay (MLB) as a potency assay for botulinum toxin.

The NIH NCATS and FDA are partners in this FOA and will collaborate and coordinate efforts with award recipients. The goal of this collaboration is to establish the Botulinum Toxin Potency Assay using Tissue Chips (BoT PATCh) as a Drug Development Tool (DDT). A main objective for this funding opportunity would be to position BoT PATCh as an alternative test method that can be utilized as a stand-alone replacement for MLB. As a cooperative agreement, small business concerns (SBCs) will be expected to work with NIH and FDA staff to develop and implement the final validation plan for the proposed alternative test method.

Key Dates

Posted Date
September 19, 2022
Open Date (Earliest Submission Date)
October 21, 2022
Letter of Intent Due Date(s)

October 21, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 21, 2022 November 21, 2022 Not Applicable March 2023 May 2023 July 2023
February 22, 2023 February 22, 2023 Not Applicable July 2023 October 2023 December 2023
August 21, 2023 August 21, 2023 Not Applicable November 2023 January 2024 April 2024

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
August 22, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) 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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) invites eligible United States small business concerns (SBCs) to submit Small Business Innovation Research (SBIR)Phase I and Phase II (Fast track and Direct to phase II) grant applications. The funding opportunity will utilize a U43/U44 cooperative agreement to support small business concerns (SBCs) to propose applications for the qualification of neuromuscular junction tissue chips (TC) as an alternative approaches method (NAM) to replace the current LD50 assay (mouse lethality bioassay (MLB) as a potency assay for botulinum toxin.

The NIH NCATS and FDA Center for Food Safety and Applied Nutrition (CFSAN) are partners in this FOA and will collaborate and coordinate efforts with awardees to help position neuromuscular junction tissue chips for use as a reliable and qualified potency assay for botulinum toxin. The goal of this collaboration is to establish the Botulinum Toxin Potency Assay using Tissue Chips (BoT PATCh) as a Drug Development Tool (DDT). Qualification of BoT PATCh as an alternative test method is needed not only for US federal agency acceptance, but also for international acceptance, and the subsequent commercialization of these test methods for products intended for global markets. This FOA is specifically intended to accelerate the development, qualification, acceptance, and commercialization of BoT PATCh that replace the use of animals in toxicological testing currently required or conducted by US federal agencies.

Applicants are encouraged to contact staff at NCATS and FDA per Agency Contacts below to ensure that their study design, qualification plan and objectives are in line with the goals of the FOA. Applicants will be expected to work with NCATS and FDA post-award to address additional testing or standards required by these agencies. These activities will be coordinated post-award through a joint NIH and FDA Steering Committee.

Background

Botulinum toxin (BoT) is a neurotoxin produced from Clostridium botulinum which in low doses is clinically effective in treating numerous medical conditions (including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine) and is also widely used for cosmetic purposes. Acetylcholine is a neurotransmitter that is released through the SNARE protein complex (synaptobrevin, SNAP-25, and syntaxin) at neuromuscular junctions by binding to the acetylcholine receptor in muscles causing the muscle fibers to contract. BoT prevents the release of acetylcholine into the synaptic cleft by cleaving one of the three SNARE proteins involved in neurotransmitter release.

Botulinum toxin can also cause the rare but life-threatening condition called botulism, characterized by weakness, blurred vision, speech impairment, muscle cramps, vomiting, diarrhea, and fever. The estimated human lethal dose of botulinum toxin is 1.3-2.1 ng/kg when administered by the intravenous or intramuscular route and 10-13 ng/kg when administered by the inhalation route.

The LD50 assay (mouse lethality bioassay (MLB)) has been the standard method to determine the safety and potency of each batch of botulinum toxin manufactured for medical and cosmetic uses. Different doses of botulinum toxin are injected intraperitoneally into a large number of mice to assess mortality following respiratory failure. MLB is a laborious and an expensive procedure requiring a sophisticated animal facility and a skilled and dedicated workforce. Additionally, ethical concerns have led to bans of the sale of cosmetic products or their components which have been tested on animals, which has led to efforts to develop alternative testing methods for the safe use of botulinum toxin in humans.

NCATS provides leadership and support of the Tissue Chips for Drug Screening program

https://ncats.nih.gov/tissuechip/about in the implementation and adoption of this technology in the drug development process. Tissue chips have emerged as a solution toward in vitro New Approaches Methods (NAMs) that are more predictive of human response in the safety and efficacy assessment of leading therapeutics. Tissue chips (TC), specifically those that recapitulate the human neuromuscular junction, provide a useful alternative platform as a NAMs for quantitative analysis and titer evaluation of botulinum neurotoxins, and also advance medical countermeasure development.

The qualification plan must include:

1. A detailed protocol for the test method and data analysis. Post review and pre-award, the Joint NCATS and FDA Steering Committee can provide further assistance in developing and/or refining a robust test method protocol for recipient review and consideration.

2. Demonstration ofNMJ markers and functions, in-vitro maintenance for longer duration,andrelevanceof microfabrication,microfluidic design, and endpoint-readoutto the BoT potency testing, as applicable.

3. Test method performance (accuracy, precision, specificity, reproducibility, ability to obtain a linear or log standard curve, etc.) criteria.

4. Plan to demonstrate test method’s performance using reference batches of BoT.

All projects (other than Direct to Phase II applications) will be Fast-Track applications which include both SBIR Phase I and Phase II components.

The duration of Phase I of the Fast-Track will depend on the maturity of the project at entry, however, duration is 6 months to one year is typical. Only those Phase I projects that have met specific criteria (see below) will be eligible for transition to Phase II of the Fast-Track after NIH administrative review. Phase II of the Fast-Track will support commercialization of BoT PATCh to replace the use of animals in toxicological testing currently required or conducted by US federal agencies.

Projects that have already demonstrated feasibility but have not received a Phase I SBIR or STTR, can apply for a Direct to Phase II award and bypass Phase I.

The SBIR U44 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.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
NEW (Phase I, Fast-Track, Direct Phase II)
RESUBMISSION (All Phases)

New (Fast Track)

New (SBIR Direct Phase II)

Resubmission (All phases)

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for the FOA.
Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials
Funds Available and Anticipated Number of Awards

NCATS intends to commit in FY2023 $325,000 to fund up to 3 phase 1 awards and $2M to fund up to 2 phase 2 awards.

NCATS

Award Budget

Total funding support (direct costs, indirect costs, fee) normally may not exceed $275,766 for Phase I awards and $1,838,436 for Phase II awards.For specific topics, NIH may exceed these total award amounts. The current list of approved topics can be found at https://seed.nih.gov/sites/default/files/NIH_Topics_for_Budget_Waivers.pdf.

Each participating component may also set their own budget limit (higher or lower than the above) in the “Limited Amount of Award Section” of their respective topics section. Applicants are strongly encouraged to contact program officials prior to submitting any application in excess of the total award amounts listed above and early in the application planning process. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project.

Budgets up to $325,000 total costs per year for Phase I and up to $2M total costs per year for Phase II may be requested

Award Project Period

According to statutory guidelines, award periods normally may not exceed 6 months for Phase I and 2 years for Phase II. Applicants are encouraged to propose a project duration period that is reasonable and appropriate for completion of the research project.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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.
  3. 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.

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. This Transition Rate requirement applies to 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. For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to be eligible to apply for a new Phase I award Fast-Track, or Direct Phase II (if available). This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that do not meet or exceed the benchmark rate 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. 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 benchmark minimum Transition Rate is 0.25.

SBA calculates individual company Phase I to Phase II Transition Rates daily using SBIR and STTR award information across all federal agencies. For those companies that have received more than 20 Phase I awards over the past 5 years, SBA posts the company transition rates on the Company Registry at SBIR.gov. Information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Applicants to this FOA that may have received more than 20 Phase I awards across all federal SBIR/STTR agencies over the past five (5) years should, prior to application preparation, verify that their company’s Transition Rate on the Company Registry at SBIR.gov meets or exceeds the minimum benchmark rate of 0.25.

Phase II to Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, 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. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537).

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. 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. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10 year period, excluding the two most recently-completed Fiscal Years.

Information on the Phase II to Commercialization Benchmark is available at SBIR.gov.

Applicants to this FOA that may have received more than 15 Phase II awards across all federal SBIR/STTR agencies over the past ten (10) years should, prior to application preparation, verify that their company’s Commercialization Benchmark on the Company Registry at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this benchmark will be notified by SBA annually and 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.

Foreign Institutions

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- are not allowed.

Required Registrations

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 Policy on Late Submission of Grant 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 Section IV. Application and Submission Information, “SF424(R&R) Other Project Information Component” 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 full SAM and Grants.gov registrations; 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

The SF424 (R&R) SBIR/STTR 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 SF424 (R&R) SBIR/STTR Application Guide.

2. Cost Sharing

This FOA 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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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.

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.

Contractual/Consortium Arrangements

In Phase I, normally, two-thirds or 67% of the research or analytical effort is carried out by the small business concern. The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 33% of the total amount requested (direct, F&A/indirect, and fee).
 

In Phase II, normally, one-half or 50% of the research or analytical effort is carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

Deviations from these requirements may be considered on a case by case basis. Please contact a program officer for additional information. Deviations must be approved in writing by the Grants Management Officer (GMO) after consultation with the agency SBIR Program Manager/Coordinator. 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 FOA. 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 SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement 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:
Rahat Khan

Telephone 301-594-7319

Email: rahat.khan@nih.gov

Page Limitations

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

1. SBIR Application Certification for small business concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g. majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive. Follow the instructions below.

Applicants small business concerns who are 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), or any combination of these (i.e. NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it their application package.

  1. Download the “VCOC Certification.pdf” at the NIH SBIR Forms webpage.
  1. Answer the 3 questions and check the certification boxes.
  1. The authorized business official must sign the certification.
  1. Save the certification using the original file name. The file must be named “SBIR Application VCOC Certification.pdf”. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.
  1. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the “Research and Related Other Project Information” form.
SF424(R&R) Senior/Key Person Profile Expanded

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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 following items.

Commercialization Readiness and Competitive Advantage. Applicants must indicate how the proposed BoT PATCh assay or approach has significant commercial potential. Preliminary data (if available) must include demonstration of method feasibility and/or comparison with in vivo data and development of Standard Operating Procedures (SOP) for the method. Applicants must also demonstrate that the proposed assay/approach has a clear advantage over existing MLB and/or competing approaches or testing strategies and must clearly define an appropriate path toward qualification as DDT and ultimate commercialization.

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 the Joint NCATS and FDA Steering Committee.

Qualification Plan.Applicants must provide a plan describing the regulatory pathway that is being or will be pursued and a timeline for achieving regulatory approval with discrete milestones. Applicants must also provide details of their consultation with the FDA in the description of their Qualification Plan. The Qualification Plan should outline a strategy that will enable federal agencies to assess the accuracy (i.e., agreement between a test method result and an accepted reference value); reliability (i.e., extent that a test method can be performed reproducibly within and between laboratories over time, when performed using the same protocol) for a specific testing purpose; and its relevance (i.e., the ability of the test method to correctly predict or measure the biological effect of interest).

The Qualification Plan must include:

1. A detailed protocol for the test method and data analysis. Post review and pre-award, the Joint NCATS and FDA Steering Committee can provide further assistance in developing and/or refining a robust test method protocol for recipient review and consideration.

2. Demonstration of NMJ markers and functions, in-vitro maintenance for longer duration, and relevance of microfabrication, microfluidic design, and endpoint-readoutto the BoT potency testing, as applicable.

3. Test method performance (accuracy, precision, specificity, reproducibility, ability to obtain a linear or log standard curve, etc.) criteria.

4. Plan to demonstrate test method’s performance using reference batches of BoT.

Studies should also include scientific and regulatory rationale for the test method, including a clear statement of its proposed use, and a detailed protocol for the test method and data analysis.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Data sharing is expected through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center. Resource Sharing Plans are expected and should indicate the plans to widely disseminate and commercialize the qualified MPS platforms.

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

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.

PHS Human Subjects and Clinical Trials Information

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.

PHS Assignment Request Form

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 Policy on Late Application Submission.

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 SF424 (R&R) SBIR/STTR 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 FOA number and title, PD/PI name, and title of the application.

Post Submission Materials
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.

For this particular announcement, note the following:

Overall Impact

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).

Scored Review Criteria

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 address an important problem or a critical barrier to progress 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 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?)

Specific to this FOA -How is the method appropriate and will lead to qualification? If the project is successful, how will the proposed NAM have a reasonable feasibility of replacing the MLB?

How will the proposed project facilitate the adoption of the BoT PATCh alternative test method by US Federal and International regulatory agencies? How does the proposed method address an important niche or broadly support alternative testing?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced 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?

Specific to this FOA- To what extent do the prior experience and qualifications of the project team members lend confidence that the team will be successful in commercializing the proposed product/technology? For example, if the PD(s)/PI(s) have had other Phase II awards, how successful have they been in commercializing those technologies and discoveries?

Do the investigators have demonstrated expertise in qualification methods? Do the investigators demonstrate knowledge of qualification requirements for FDA and International regulatory agencies?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA - Does the proposed neuromuscular junction tissue chip platform possess the necessary physiological and functionality to reasonably replace MLB? Is there evidence that proposed BoT PATCh will be qualified and adopted as appropriate to assure advances in NAMs and promoting a new DDT?

Approach

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?

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?

Specific to this FOA- Does the approach enable the assessment for the accuracy (i.e., agreement between a test method result and an accepted reference value); reliability (i.e., extent that a test method can be performed reproducibly within and between laboratories over time, when performed using the same protocol) for a specific testing purpose; and its relevance (i.e., the ability of the test method to correctly predict or measure the biological effect of interest)?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional 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?

Specific to this FOA- To what extent does the applicant's environment facilitate their ability to address US federal agency requirements, either through their own staff members or through appropriate arrangements with external consultants?

COMMERCIALIZATION PLAN

How well has the applicant demonstrated an understanding of the competitive environment in which they plan to sell their product? How well has the company addressed potential hurdles that may delay or prevent acceptance of their alternative test method as a product? How strong is the applicant’s intellectual property (IP) portfolio/position (pertinent to the proposed project), and to what extent does the company have a reasonable strategy to protect its IP going forward?

Has the applicant included a realistic plan, which outlines how qualification will expedite commercialization as well as when full commercialization can be accomplished? Has the applicant included possible strategic collaboration and partnerships to further the adoption and commercialization of their IP?

Data sharing is expected through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center. Resource Sharing Plans are expected and should indicate the plans to widely disseminate and commercialize the qualified MPS platforms. 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.

Additional Review Criteria

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. 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?

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 Animal 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.

Additional Review Considerations

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

Reviewers will consider whether work to be performed outside of the United States is thoroughly justified, based on a rare and unique circumstance, and necessary to the overall completion of the project.

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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan.

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.

Will receive a written critique.

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

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 FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate 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.

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 VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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.5. 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 FOA 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:

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 must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please 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 FOA.

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.

Report fraud, waste and abuse

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.

Cooperative Agreement Terms and Conditions of Award

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 45 CFR Part 75, 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 awardees 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 and FDA as defined below.

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

Defining the details and goals of the project as a whole within the guidelines of this FOA.

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

Submitting quarterly progress reports in a format as agreed upon with the NCATS Program Officer and Project Scientist.

Accepting and implementing any other common guidelines and procedures developed for the Joint NCATS and FDA Steering Committee.

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

Attending bi-annual workshops organized by the NIH and FDA.

Managing all data acquired in a coherent database that will be available to government and private partners.

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

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 policies.

Identifying and maintaining infrastructure and collaborations needed to support the development of the proposed MPS model for qualification.

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

Working with the NCATS and FDA through the Joint NIH and FDA Steering Committee towards establishing context of use, standardizing and qualification approaches.

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 FOA.

Participating in a cooperative and interactive manner with NIH and FDA staff, and other BoT PATCh award recipients

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

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. However, NIH still expects SBIR applicants toaddress 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 FOA.

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. The data sharing plan should include a plan to accomplish this within 90 days of the end of the study and plans for data submission through the Microphysiological Systems Database at the University of Pittsburgh.

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 Project Scientist 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.

Communication Plans

The Principal Investigator(s) will be responsible for:

Participating in regular (monthly) conference calls with all NIH and FDA Project Team members.

Coordinating efforts with other award recipients, especially in circumstances where synergy of efforts and resources is beneficial to the overall goals of the BoT PATCh program.

Participating and presenting findings at the semi-annual workshops convened by the NIH and FDA.

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.

NCATS will designate program staff, including a Program Officer, to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer will be named in the Notice of Award (NoA). The Program Officer in consultation with the Joint NIH and FDA Steering Committee will make the final determination on the negotiated milestones and will also make the final determination on whether the milestones are met.

NIH Tissue Chip 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; the NIH Tissue Chip Project Scientists will facilitate and not direct the activities of the team.

Specifically, the NIH Tissue Chip Project Scientist 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 Project Scientists from 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 awardee 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 awardee with others engaged in MPS research, including other awardees under this FOA and those awardees 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 awardee institutions who are to serve as External Scientific Consultants, as needed.

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

Work directly with industry and regulatory partners on maintaining or modifying standardized protocols to test MPS devices.

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 awardees 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 FOA.

The Program Officer and the designated FDA Point of Contact along subject matter experts will make up the Joint NIH and FDA Steering Committee. The committee will work with the award recipients in providing scientific and regulatory guidance for consideration of applicable expectations to achieve regulatory qualification of BoT PATCh as a DDT.

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 Funding Opportunity Announcement.

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

The NIH will enlist additional scientific experts as necessary from within the NIH, other government agencies, such as the FDA, and from industry partners, such as IQ MPS Affiliate, whose function will be to assist the Program Director in carrying out the goals and aims of the approved studies.

Data

Intellectual Property

The successful development of qualified MPS platform and the integration of these microsystems within a common platform 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 awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.

The awardee 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).

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 awardee. This special dispute resolution procedure does not alter the awardee'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. Reporting

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. 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.

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI. NIH FOAs 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.

Section VII. Agency Contacts

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

Application Submission Contacts

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: http://grants.nih.gov/support/ (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: 301-945-7573

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

Scientific/Research Contact(s)

Danilo A. Tagle, Ph.D.

Office of Special Initiatives
National Center for Advancing Translational Sciences, NIH

Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Lili M. Portilla, M.P.A.

SBIR/STTR Program Director

Office of Strategic Alliances

National Center for Advancing Translational Sciences, NIH

Phone: 301-827-7170

Email: Lilip@nih.gov

Shashi Sharma, Ph.D.

Molecular Methods and Development Branch

Division of Microbiology, Office of Regulatory Science

US Food and Drug Administration

Phone: 240-401-1570

Email: Shashi.Sharma@fda.hhs.gov

David A. Jett, Ph.D.
National Institute of Neurological Disorder and Stroke (NINDS)
Telephone: 301-496-6035
Email: jettd@ninds.nih.gov

Peer Review Contact(s)

Rahat Khan, Ph.D.

National Center for Advancing Translational Sciences, NIH

Phone: 301-594-7319

Email: rahat.khan@nih.gov

Financial/Grants Management Contact(s)

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

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.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.

Authority and Regulations

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, and P.L. 115-232. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

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