Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)

Funding Opportunity Title

NextGen Tissue Chip Testing Centers: Validating Microphysiological Systems (U24 Clinical Trial Not Allowed) 

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-TR-18-006

Companion Funding Opportunity

RFA-TR-18-005

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.350 

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications for NextGen Tissue Chip Testing Center(s) (NextGen TCTC) that will provide resources and infrastructure for the validation of tissue chips being developed as part of the NIH Tissue Chip (TC) for Drug Screening Program or NIH Microphysiological Systems (MPS) Program. The MPS program supports a consortium of investigators developing accurate cellular and organ microsystems representative of human physiology for the evaluation of drug efficacy and toxicity (RFA-RM-11-022; RFA-TR-16-017; RFA-TR-16-019).  The developed in vitro MPS platforms are representative of major organs and tissues in the human body, and need to be validated for their predictive capabilities of the assessment of biomarkers, and the bioavailability, efficacy, and toxicity of therapeutic agents prior to entry into clinical trials.  Validation of the tissue chips is currently being conducted through Tissue Chip Testing Centers. These are responsible for testing a select group of compounds using predefined assays and biomarkers, according to pharmaceutical industry standards, and the integration of the data into a public database. NextGen TCTC(s) will aim to accelerate the transition of NIH-supported research innovations and technologies toward a self-sustaining model to continue the validation of various MPS platforms. NextGen TCTC(s) will develop services that promote the use of MPS by industry, regulatory bodies, and biotech sectors, and create significant value and economic stimulus or, advance the research in MPS technology in a way that could stimulate future growth and investments, and advance drug discovery and development. This U24 is intended to support research and development (R&D) specifically targeted at activities that can help address the funding gap between promising R&D and transitioning to the market, often called the “Valley of Death” by contributing the critical funding needed by applicants to pursue the next appropriate milestone(s) toward commercialization; and to foster partnerships among a variety of research and development (R&D) collaborators working toward these aims.     

Key Dates
Posted Date

December 20, 2017

Open Date (Earliest Submission Date)

February 21, 2018

Letter of Intent Due Date(s)

February 21, 2018

Application Due Date(s)

March 21, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement.

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.

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

June 2018

Advisory Council Review

August 2018

Earliest Start Date

September 2018

Expiration Date

March 22, 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. 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. Funding Opportunity Description

    Background

    Microphysiological systems (MPS), or tissue chips, are microfabricated devices that mimic human physiological responses, and will be useful tools for predictive toxicology and efficacy assessments of candidate therapeutics. The MPS program started as a five-year partnership with NIH, DARPA and FDA. Previous NIH FOAs (RFA-RM-11-022) and (RFA-RM-12-001) supported the development and integration of bioengineered organ systems, along with the generation of renewable human cell resources to be used as an effective tool for drug development. These organ chip systems consist of scaffolding and multi-cellular tissues with inclusion of mechanical factors (such as flow and stretch) to recreate physiological conditions. Integrating them with other MPS devices to better study organ-organ interaction adds another layer of in vivo-like conditions not available in current in vitro models. Data acquired from this program suggest that tissue chips have the potential to more accurately reflect human responses than current in vitro and animal models, and could have a substantial impact on the safety and efficacy testing of candidate therapeutics. The overarching goal of the NIH Tissue Chip Program is to develop these MPS devices and integrate them to create a Human-on-a-Chip for drug efficacy and safety assessment prior to clinical trials.  Current NIH-funded MPS research focuses on modeling diseases for efficacy testing (RFA-TR-16-017), and also includes a partnership between NCATS, NASA and CASIS (RFA-TR-16-019). Through RFA-TR-016-006, Tissue Chip Testing Centers and a Tissue Chip Database Center (TCTCs and TCDC) were established to investigate replicability of tissue chip technology and to promote adoption by the research community by validating tissue chip platforms.

    Purpose

    The purpose of this FOA is to facilitate the transition of previously funded TCTC projects to the commercialization stage by providing 1-2 year(s) of support for later stage research and development (R&D) activities necessary for the wider adoption and use of MPS in drug development by research scientists, pharmaceutical companies and regulatory bodies. This may include independent replication of key studies from NIH and non-NIH supported MPS platforms and technologies, improving/standardizing assays, developing best practice guidelines and SOPs for chips of high priority. Additionally, this may also include the provision of services towards Investigational New Drug (IND)-enabling studies using TC data, improving manufacturing costs based on prior experience in various TC platforms, regulatory assistance, or a combination of services related to TC development. In addition, the NextGen Tissue Chip Testing Center(s) can fully utilize tissue chip technology in drug discovery and development by forging an integrative strategy using MPS to be directed at a critical unmet medical need for which historical approaches have been unproductive – e.g. a comprehensive and definitive array of assays and biomarker testing on MPS for cardiotoxicity to evaluate heart failure therapy. 

    The NextGen Tissue Chip Testing Center(s) will have the requisite infrastructure, prior experience in validating various MPS, data management and statistical capabilities, as well as responsibility for administrative coordination of activities with the MPS investigators related to the independent validation of tissue chips, which may include qualification with the FDA for use in the regulatory-decision process. They will also be responsible for seeking commercial end users, and providing documentation and evidence that the Center can become a self-sustaining enterprise beyond the 1-2 year(s) of NIH support.

    The FDA defines validation “as a process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in production or testing maintains the desired level of compliance at all stages” and will consistently produce the expected results. In the context of the NextGen TCTC(s), validation is defined as utilizing standardized methodologies and predefined reference test compounds, vetted by pharmaceutical representatives, to run tests in replicate and determine functionality, reproducibility, robustness and reliability in these organ platforms. Tissue chip validation is also congruent with the NIH’s emphasis on reproducibility, rigor and robustness. Rigorous organ chip testing will demonstrate to potential stakeholders and regulatory agencies that the technology can be utilized as a better predictive model for assessing safety and efficacy of promising therapies than currently accepted standards.

    To fully implement the validation and commercialization process of tissue chip platforms, NextGen TCTC scientists will rely on TC platform expertise and resources (protocols and reference compounds) developed by the TC Consortium, which includes government officials, industry representatives, and tissue chip developers. NIH will continue to expand on private-public relationships, working with industry and other potential stakeholders to provide TCTC metrics, protocols and guidelines.

    In order to maximize scientific exchange and accelerate research in the context of tissue chip technology, it is expected that all information, data, protocols and methods used for validation be shared in a timely manner with the TC Consortium, which includes the MPS DC (see related FOA RFA-TR-18-005), and with industry partners.

    Structure of the Tissue Chip Consortium (The TC Consortium)

    The NIH Tissue Chips for Drug Screening Program, Chips in Space program and Tissue Chip Testing/Database Centers programs are led and managed by NCATS and utilize expertise (organ physiology, regulatory science, stem cells, bioengineering, etc.) from more than 60 experts representing over 15 Institutes, Centers and Offices at the NIH and the FDA. NIH interaction with the IQ Consortium allows for pharmaceutical companies to work with NCATS staff and TC investigators on context of use, marketability and potential stakeholder feedback, elements crucial to move past the discovery/innovation phase. The TC Consortium, which comprises all these programs and partnerships, plus several new industry collaborators, meets every 6 months and plays a pivotal role in advancing the MPS technology.  

    NextGen Tissue Chip Testing Center(s)

    The NextGen TCTC(s) will work directly with the TC Consortium, composed of tissue chip technology developers, government officials, industry representatives and other potential partners, and which originated from the Tissue Chip for Drug Screening program (RFA-RM-11-022).  The NextGen TCTC(s) will be milestone-driven, actively work with the TC Consortium and TC Developers to test MPS devices, acquire, store and use a standard set of tissue resources and test compounds for device validation, and share data/methodology with the TC Consortium.  It is also expected that NextGen TCTC(s) will create a revenue stream such that it is self-sustaining beyond the 1-2 years of NIH support. 

    Partnerships

    A key aspect of this award is the interactions among NextGen TCTC(s) PD/PIs, TC Developers, MPS Data Center PD/PIs, NIH Officials and Industry Partners.  NCATS has executed a Memorandum of Understanding (MOU) with the IQ Consortium (https://iqconsortium.org), with membership consisting of several pharmaceutical companies, and will rely on their feedback regarding vetted reference compounds and functional readouts/assays for each organ system. 

    Template agreements have been developed for this program to streamline the process: Confidential Disclosure Agreements (CDAs, https://ncats.nih.gov/files/CDA-tissue-chip-validation.pdf) and Collaborative Research Agreements (CRAs, https://ncats.nih.gov/files/CRA-tissue-chip-validation.pdf) will provide the framework for partnership between the TC Developer and NextGen TCTC PD/PI.  NextGen TCTC applicants are expected to work with their institutional technology transfer or sponsored research office regarding the terms and conditions of the CDA and CRA with the TC Developers. For NextGen TCTC PD/PIs and TC PD/PIs (who are awardees of RFA-RM-11-022, RFA-RM-12-001, RFA-TR-16-017, and RFA-TR-16-019) and/or among multi-PD/PIs, a conflict management plan must be included in the agreement. Projects should be supported by robust plans for revenue-generating activities beyond the 1-2 years of NIH support, and documentation of an executed CDA and CRA between the respective parties prior to receipt of the Notice of Award. 

    Intellectual Property

    TC Developers will retain title to any patent or other intellectual property rights in inventions made in the course of the performance of the TC Program. If TC Developers and NextGen TCTC investigators make modifications of TC platforms that significantly change performance and/or function, both parties are expected to discuss ownership interests where applicable and consistent with Licensing of US Government Owned Inventions regulations as specified in 37 CFR 404, and to negotiate in good faith the terms of a commercial license. Inventorship for a patent application or a commercialized product based on said inventions will be determined according to United States patent law.

    All rights, title and interest in and to any inventions or technologies of TC Developers or of NextGen TCTC investigators, respectively, existing prior to receiving NIH grant funds will be the exclusive property of the respective party. Furthermore, all rights, title and interest in and to any inventions or technologies developed by TC Developers or NextGen TCTC investigators not directly arising from the project plan described in the collaboration agreement will be the exclusive property of the respective party. TC Developers must agree to disclose developed intellectual property promptly and fully to NextGen TCTC investigators.      

    Data/Information Ownership and Disclosure: NextGen TCTC investigators will own such copies of TC validation project data and relevant reports and may use them for any purpose in accordance with applicable laws, provided, however, that NextGen TCTC PD/PI’s do not publicly disclose information derived from the project data or contained in such reports without prior written permission of TC Developers and NIH. 

    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 scientific or program 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

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials.

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NCATS intends to fund 1-2 TCTC awards committing up to $4 million in FY 2018 and $4 million in FY2019. Future year funds are dependent on annual appropriations.

    Award Budget

    Application budgets are limited to $1 million in direct costs per year.

    Award Project Period

    The maximum project period is 2 years.

    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

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    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, as defined in the NIH Grants Policy Statement, 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.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) (formerly CCR) – 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.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    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.

    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

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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 NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms 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 Research (R) Instructions in the SF424 (R&R) 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.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    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:

    Carol Lambert, Ph.D.
    Telephone: 301-435-0814
    Fax: 301-480-3660
    Email: lambert@mail.nih.gov

    Page Limitations

    All page limitations described in the SF424 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) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

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

    Facilities & Other Resources. Document the availability of resources, staff expertise and infrastructure to perform all studies without delay. Document previous experience in testing and validating a number of tissue chip platforms. Document the availability of and access to GLP-like facilities, infrastructure, conditions and practices (for example, dedicated personnel for QA, framework of SOPs, training of staff for GLP, qualification of instruments, quality control of results and reports and archiving). Although GLP-certified locations are not required, facilities that perform assays under GLP-like conditions are strongly preferred. Document institutional experience working with iPSC lines and capabilities of storing several iPSC lines that will be utilized in numerous TC platforms. Document any unique features of institutional support.  Document institutional support towards the transition to a self-sustaining enterprise.

    SF424(R&R) Senior/Key Person Profile

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

    Applicants should document the following in the biosketches:

    • Track record of the PD/PI in technology transfer.
    • Experience of the PD/PI in working with members of the Tissue Chip Consortium and associated stakeholders.
    • Experience of the PD/PI with numerous assays complying with standardized guidelines.
    • Experience with high capacity/high throughput capabilities.
    • Track record regarding toxicity testing and standardization protocols.
    • Flexibility and adaptability to deal with multi-layered concepts like pharmacokinetics/ pharmacodynamics (PK/PD), dosing regimens, organ physiology and toxicology, etc.
    • Experience in handling, QC, stabilization, storage etc. of chemicals/compounds.
    • Track record in establishing rigor, reproducibility and replication of data.
    • Experience in in vitro and in vivo toxicity testing.
    • Expertise in informatics, analysis, database management, and customization of software.
    • Prior experience/track record of interfacing with academic investigators, industry and regulatory agencies.
    • Experience in 3D cell culture, iPSC lines, and other cell sources.
    • Collaborations and partnerships with industry, biotech companies, and other government agencies that demonstrate ability to be self-sustaining financially, as well as in scientific directions in keeping tissue chip approaches paramount in drug development.
    R&R Budget

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

    Budgets should reflect and document existing infrastructure that is capable of performing GLP-like practices.

    Funds may be requested for the following types of activities:

    • Independent replication/confirmation of key studies
    • Activities to ensure compliance with applicable FDA requirements
    • Activities to bring the development process under Design and Quality Systems Control
    • Implementation of standardized testing protocols (established by government and industry partners for each organ platform) and formatted test readouts.
    • Development and transfer of tissue chip devices to the Testing Center (applicant organization).
    • Validation of organ chip systems using a minimum of 5-7 reference compounds and 5-7 assays, replicated a minimum of 3 times.
    • Further development of tissue chip technology in drug discovery and development by forging an integrative strategy using MPS to be directed at a critical unmet medical need for which historical approaches have been unproductive – e.g. a comprehensive and definitive array of assays and biomarker testing on MPS for cardiotoxicity to evaluate heart failure therapy. 
    • Extending the utilization of MPS beyond drug development, such as in environmental toxicity assessment
    • Optimization of the device design with respect to representing the human functional anatomy and physiology
    • Identification of the most simple, reliable, and cost-effective device configuration for more advanced clinical trials and eventual market approval
    • Process optimization and synthesis, including development of analytical methods
    • IND-enabling studies, including toxicology and pre-clinical assessments
    • Chemistry, Manufacturing, and Control (CMC) activities for IND-enabling pharmacology/toxicology tests
    • Pharmacokinetic/ADME (absorption, distribution, metabolism, excretion) studies
    • Tumorigenicity, immunogenicity, mutagenicity and teratogenicity evaluations

    PDs/PIs are required to participate in twice-yearly Consortium Meetings. Funds to support travel of the PD(s)/PI(s) to attend the twice-yearly Consortium Meetings should be included in the budget, and are not to exceed $3000 direct costs per meeting, per attendee.

    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Research Strategy: The following items should be addressed by the applicant in the research strategy:

    • A value proposition based on a review and analysis of the benefits, costs, and value that the organization can deliver to its customers.
    • Compounds supplied by TC industry partners.
    • Consideration of factors that influence performance metrics and sources of variance to guarantee reproducibility and reliability of TC devices.
    • Ability to work with TC investigators, government officials and industry partners to acquire reagents and cell sources for TC testing, including, but not limited to iPSC lines, predefined testing compounds, cellular matrices, media, etc.
    • Access to an array of chemicals and reagents needed to perform the various TC assays.
    • Ability to store, register and track use of reagents, chemicals and tissue sources.
    • Ability to check quality and control of reagents, chemicals and tissue sources.
    • Strategy to work with TC investigators, government officials, industry partners and other potential partners to determine what assays will be used to test each organ system.
    • Ability to address challenges in widespread adoption and use of MPS in drug development 
    • Strategy to engage and partner with pharmaceutical companies, biotechnology industries, government agencies and other stakeholders 
    • Strategy and approach to transition into a self-sustaining model 

    Milestones

    Applicants must provide a set of milestones and timelines that demonstrate they will be able to accomplish scientific objectives, specifically, generate outputs and data needed to validate TC systems. Milestone-driven goals and timelines should incorporate quantitative success criteria that facilitate go or no/go decisions. In the context of this FOA, milestones should be designed to keep progress on track for the 2-year project period. Possible obstacles and how they will be overcome should also be addressed.

    Proposed milestones should include Go/No Go decision points and include target completion dates and success criteria. They should address the following:

    • Timely acquisition of organ platform systems and accompanying hardware/software and cell resources from the TC Developers
    • How informatics will be put in place to manage resources, assays, compounds and data, including ensuring availability of source code and data format to the MPS DC and the rest of the TC Consortium.
    • If additional validation of platforms or compounds will be part of the proposed research, please address the following:
    • ·    Indicate which organ platforms will be tested in addition to those validated at the current TCTCs and the time line to fully complete validation.
    • ·    It is anticipated that NextGen TCTC(s) should aim to validate organ chip systems using a minimum of 5-7 reference compounds, 5-7 assays, and replicated a minimum of 3 times.
    • If further research and development is being proposed to fully utilize tissue chip technology in drug discovery and development, through an integrative strategy using MPS to be directed at a critical unmet medical need for which historical approaches have been unproductive, please address the following: 
    • ·    Engagement of key stakeholders and/or corporate partnerships in developing and implementing integrative strategy
    • ·    Include key tasks to be performed and success criteria with precise, quantifiable and objective measures of success
    • Incorporate in the milestones the planned activities and benchmarks necessary for the transition into a self-sustaining model
    • Provide a Gantt chart illustrating the proposed project schedule

    Communication and Collaboration

    Applicants should address the following:

    • How the proposed NextGen TCTC sites can develop and/or modify current assays used to assess safety and toxicity readouts in order to adapt them for TC evaluation. NextGen TCTC investigators cannot modify the actual organ platform, but can provide advice to TC developers on improvements based on usage and experience of said platform.
    • Dosing regimens for each test compound/organ system should be included in the testing protocols.
    • How NextGen TCTC investigators will work with the MPS Database Center to organize the web-based dissemination of TCTC-related information and develop a means to access validated data and resources generated by the NextGen TCTC research projects, including experimental models, protocols, biomaterials, resources, reagents and omics- and image-based data collections.  Applicants should address data sharing plans and development of SOPs for data managements with the MPS DC. Transfer of TC platforms, resources and reagents can be done through the individual laboratories or by depositing the materials in an appropriate resource facility.
    • Strategy to leverage resident expertise in toxicity testing and organ physiology, and the ability to integrate additional requisite experts as consultants.
    • How NextGen TCTC investigators will work with TC investigators, government officials and industry partners to acquire reagents and cell sources for TC testing, including, but not limited to, iPSC lines, predefined testing compounds, cellular matrices, media, etc.
    • How NextGen TCTC(s) will work with TC investigators, government officials and industry partners to determine what assays will be used to test each organ system.

    Plan for self-sustaining operations

    Applicants are expected to seek additional resources to maintain their operations and continue to have an impact after NIH funding ends. Plans should indicate other sources of support for program sustainability, and include descriptions of all institutional support, financial and collaborative arrangements, and/or agreements for payment for services. Appropriate documentation should be included in the application. Provide any other relevant information about the applicant’s approach for self-sustaining infrastructure and operations.

    Readiness to Undertake Validation Activities

    Applicants should address the following:

    • The capacity to scale up operations and the approach to doing so if the need arises.
    • Documentation that NextGen TCTC investigators have access to an array of specialized chemicals and reagents needed to perform the various TC assays; the ability to store, register and track use of reagents, chemicals and tissue sources; the ability to check quality and control of reagents, chemicals and tissue sources.

    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:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. This plan is expected to include addressing timely data release to the MPS DC, TC Government Officials and TC Developers as determined by the NextGen TCTC Program Director(s)/Principal Investigator(s) (PD/PI) during the course of the award, and more broadly to the research community at the conclusion of the award as appropriate and consistent with achieving the goals of the program.
    • The sharing plan must include an agreement that NextGen TCTC investigators will work collaboratively with the TC Consortium to maximize research accomplished by the program, and to implement procedures to provide quality controlled data and information. This will include utilization of MPS DC database that will be accessible to the TC Consortium. The site will have general open accessibility with some restricted access components related to individual TC projects. Data acquired from TC testing will be shared individually/specifically with TC Developer.
    • Applicants must commit to sharing and making protocols/methodologies, data, biomaterials, models, reagents, tools, and resources available to the other TC Consortium members as appropriate and consistent with achieving the goals of the program. The terms and timelines for sharing within the NextGen TCTC validation project; adjustments for coordination of research plans, validation of models, materials, methods and data.  Sharing with the research community will be established by the NextGen TCTC PD/PI and approved by the NCATS Tissue Chip Program Director, consistent with achieving the goals of the program and applicable NIH policies. All participants must adhere to these terms as a condition of award.
    • Upon completion or termination of the research project(s), the TCTC awardees will be responsible for making all data and procedures available to the TC Consortium, as well as making them broadly available (e.g., putting them into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project. The resource sharing plan must include a plan to accomplish this availability and accessibility no later than at the end of the project period or as negotiated with the NCATS Tissue Chip Program Director.

    Appendix:

    Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.  

    PHS Human Subjects and Clinical Trials Information 

    Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) 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 a 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

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

    PHS Assignment Request Form

    All instructions in the SF424 (R&R) 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), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. 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) 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) 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 Component of the SF424(R&R) Application Package. 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. See Section III of this FOA for information on registration requirements.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number 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. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center 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 Center 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 proposed Center address the needs of the research projects that it will serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research consortium?

    Specific to this FOA: Does the information provided suggest that the NextGen Testing Center can be sustained beyond the proposed funding period? How well has the applicant addressed potential hurdles in the widespread use of MPS?   

    Investigator(s)

    Are the PD(s)/PI(s)/Directors and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing tissue chip research? Do the investigators demonstrate significant experience with coordinating collaborative preclinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their plans for conflict resolution appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

    Specific to this FOA: Does the PD/PI have a proven record of technology transfer? Does the PD/PI have experience in working with members of the Tissue Chip Consortium or comparable groups and associated stakeholders? Does the PD/PI have experience with numerous assays complying with standardized guidelines?   

    Innovation

    Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research projects the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed? 

    Specific to this FOA: If the applicant is proposing development of a comprehensive and definitive array of assays and biomarker testing on MPS, how innovative and relevant is the proposed R&D for the translational problem being addressed?   

    Approach

    Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research consortium the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the consortium, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the consortium? Are an appropriate plan for work-flow and a well-established timeline proposed?  Have the investigators presented adequate plans to ensure consideration of biological variables, such as sex, for studies of vertebrate animals or human subjects?

    Specific to this FOA: Are appropriate goals and timelines in place to test at least 12 organ systems by the end of the project using multiple replicates, a predefined battery of assays, and a pre-identified set of validation compounds supplied by TC industry partners? Are adequate plans to test limits and sensitivity of each TC system, and compare to current in vitro and in vivo gold standards described? Do the testing protocols include appropriate dosing regimens for each test compound/organ system? Are there appropriate milestones that ensure timely completion of the project? As part of the validation efforts, is there convincing evidence that factors that influence performance metrics and sources of variance are taken into consideration to guarantee reproducibility and reliability of TC devices?

    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 children, justified in terms of the scientific goals and research strategy proposed?  

    Environment

    Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research consortium it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel?  Are resources available within the scientific environment to support electronic information handling?

    Specific to this FOA: Is there convincing evidence that applicants have infrastructure in place to conduct and improve upon organ/TC-specific assays that fit context of use for each organ system? Do the proposed facilities have appropriate experience working with iPSC lines and capabilities of storing several iPSC lines that will be utilized in numerous TC platforms? Is there evidence of unique features of institutional support?  Does the institute promote and provide support towards the transition to a self-sustaining model?   

    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.

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the six 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 six 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 Children 

    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 children 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

    Not Applicable.

    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 from Foreign Organizations

    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 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 (GDS).

    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:

    • May undergo a selection 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  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 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.
    • Compliance with resource sharing policies.
    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 grantee’s business official.

    Awardees 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.

    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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    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 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees 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 as a whole within the guidelines of this FOA.
    • Managing all data acquired in a coherent database that will be available to government and private partners.
    • Coordinating, cooperating, and participating with NIH staff in the scientific, technical, and administrative management.
    • Designating and maintaining infrastructure for the sole purpose of a tissue chip testing center.
    • Working with private partners to acquire and maintain reference compounds that industry partners will provide.
    • Working with NIH Program Officials and industry partners to establish context of use, standardizing and validating approaches. 
    • Performing established standardization and validation milestones.
    • Acquiring microphysiological devices from tissue chip researchers and working with them to understand the perimeters/context of use for each system.
    • Ensuring that all NextGen TCTC-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.
    • Along with all NextGen TCTC-affiliated staff, participating in a cooperative and interactive manner with the MPS Data Center, NIH staff, TC investigators and one another.
    • Sharing data, materials, informatics tools, methods, information and unique resources that are generated by the project as appropriate and in accordance with NIH policies in order to facilitate progress and consistent with achieving the goals of the MPS program.
    • Working with the members of TC Consortium, including the MPS DC 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 undertaken by the NextGen TCTC that involve academic and/or industry collaborations within 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 Funding Opportunity Announcement.
    • Upon completion or termination of the NextGen TCTC project, ensuring all study materials, tools, databases and procedures developed by the TCTC are broadly available (e.g., putting into the public domain) or make them 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.
    • Implementing a sustainability plan at the conclusion of NIH support.

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

    The 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).

    An NIH Project Coordinator will be substantially involved in this project as follows:

    • Coordinate and facilitate the activities of the NextGen TCTC, attend and participate in all meetings of the TCTC, and act as a liaison between the Awardee and the Cures Acceleration Network Review Board (CAN RB).
    • Work with Science Officer(s) from the trans-NIH TC Project Team, to review the scientific progress and administrative accomplishments of the NextGen TCTC, 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.
    • Maintain public - private partnerships established under the NCATS Tissue Chip initiative
    • 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 NextGen TCTC adheres 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 NextGen TCTC
    • Provide advice on project management and technical performance.
    • Coordinate and manage NextGen TCTC Steering Committee efforts
    • Provide guidance to the awardees on private-public partnerships and regulatory agency policies
    • Invite experts with relevant scientific expertise to provide feedback on NextGen TCTC activities.
    • The NIH reserves the right to curtail or phase out the NextGen TCTC 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 TCTC procedures and milestones, and/or (3) substantive changes in the management of TCTC that are not in keeping with the objectives of the FOA.
    • The NIH will enlist additional scientific consultants as necessary from within the NIH, other government agencies, such as the FDA, and from industry partners whose function will be to assist the NextGen TCTC Program Director in carrying out the goals and aims of the approved studies.

    Areas of Joint Responsibility include:

    • Through the NextGen TCTC awardee(s) and NIH staff, TCTC 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 NextGen TCTC-related issues and/or activities.
    • Engage the CAN RB to provide feedback to the NCATS on NextGen TCTC activities. The CAN RB may review the progress of the TCTC project and may advise NIH staff of opportunities that may enhance the operation and achievements of the TCTC.

    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 from the Cures Acceleration Network Review Board 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

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

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees 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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 Appendix XII to 45 CFR Part 75 – Award Term and Conditions 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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Scientific/Research Contact(s)

    Danilo Tagle, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-594-8064
    Email: tagled@mail.nih.gov

    Peer Review Contact(s)

    Carol Lambert
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-435-0814
    Email: Lambert@mail.nih.gov   

    Financial/Grants Management Contact(s)

    Ki-Cha Flash
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-435-0864
    Email: Ki-Cha.Flash@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 42 CFR Part 52 and 45 CFR Part 75.

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