Required Application Instructions

It is critical that applicants follow the 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.

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

Microphysiological systems (MPS), or tissue chips, which are micro-fabricated devices that mimic human physiological responses, will be useful tools for predictive toxicology and efficacy assessments of candidate therapeutics. The MPS program is a five-year partnership among 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, multi-cellular tissues and 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.

The purpose of this FOA is to establish Tissue Chip Testing Centers (TCTC) to ensure availability of tissue chip technology and promote adoption by the research community by validating tissue chip platforms. The Tissue Chip Testing Center(s) will have the requisite infrastructure, 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.

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. In industry it is very important apart from final testing and compliance of product with standard that the process adapted to produce itself must assure that process will consistently produce the expected results. In the context of the TC, validation is defined as utilizing standardized methodologies and predefined reference test compounds vetted by pharmaceutical representatives to run tests in replicate to determine functionality, reproducibility, robustness and reliability in these organ platforms. Tissue chip validation is also congruent to the NIH emphasis on reproducibility, rigor and robustness because scientists not currently part of the TC consortium will do these efforts independently at different locations. 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 current accepted standards being used in research in human health and disease.

To fully implement the validation process, TCTC scientists will rely on TC platform expertise and resources (protocols and reference compounds) developed by the TC Consortium that 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, and with industry partners.

The NIH TC for Drug Screening Program is led and managed by NCATS and utilizes 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 partnerships, plus several new industry collaborators, meets every 6 months and plays a pivotal role in advancing the MPS technology.

Tissue Chip Testing Center

The Tissue Chip Testing Center (TCTC) will work directly with the Tissue Chip Consortium, composed of tissue chip technology developers, government officials and industry representatives, and which originated from the Tissue Chip for Drug Screening program (RFA-RM-11-022). The TCTC 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.

Partnerships

A key aspect of this FOA is the interactions among TCTC PD/PI, TC Developers, 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 TCTC PD/PI.  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 TCTC PD/PI and TC PD/PI (who are awardees of RFA-RM-11-022 and RFA-RM-12-001), and/or among multi-PD/PI, a conflict management plan must be included in the agreement. A successful application will be contingent on the applicant s ability to provide the NIH with documentation of an executed CDA and CRA between the respective parties prior to receipt of the Notice of Award. 

Intellectual Property

TC investigators 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 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 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 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 TCTC investigators.

Data/Information Ownership and Disclosure: 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 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.

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

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH 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.

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.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

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:

Mohan Viswanathan, Ph.D.
Telephone: 301-312-3745
Fax: 301-480-3660
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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.

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

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. A summary of current organ chip metrics and assays can be found here: https://ncats.nih.gov/files/specs-tissue-chip-validation.xlsx

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, but lack GLP-certification). Although GLP-certified locations are not required, facilities that perform assays under GLP-like conditions are strongly preferred.

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

Applicants should document the following in the biosketches:

• 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.

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 should be requested for:

• 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.

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

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

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

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:

• 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 and industry partners to determine what assays will be used to test each organ system.

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 address:

• Timely acquisition of organ platform systems and accompanying hardware/software and cell resources from the TC Developers, for example, within the first 3 months
• How informatics will be put in place to manage resources, assays, compounds and data within the first 1-2 months after the performance period starts, including ensuring availability of source code and format to the TC Consortium.
• How testing of 2-3 organ platforms will be accomplished during the first 6 months
• How a pace of completed testing on 2-3 new devices every 6 months will be achieved and maintained
• How testing all tissue chips will be completed by the end of the 2-year performance period.
• Note: It is anticipated that TCTC will be validating organ chip systems using a minimum of 5-7 reference compounds and 5-7 assays, and replicated a minimum of 3 times.

Communication and Collaboration

Applicants should address the following:

• How the proposed TCTC sites can develop and/or modify current assays used to assess safety and toxicity readouts in order to adapt them for TC evaluation. TCTC investigators cannot modify the actual organ platform.
• Dosing regimens for each test compound/organ system should be included in the testing protocols.
• How TCTC investigators will organize the web-based dissemination of TCTC-related information and develop a means to access validated data and resources generated by the TCTC research projects, including experimental models, protocols, biomaterials, resources, reagents and omics- and image-based data collections. 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 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 TCTC will work with TC investigators, government officials and industry partners to determine what assays will be used to test each organ system.

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 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, must include a Resource Sharing Plan. This plan must include timely data release to the TC Government Officials and TC Developers as determined by the TCTC Program Director during the course of the TCTC 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 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 a TCTC 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 TCTC validation project; adjustments for coordination of research plans, validation of models, materials, methods and data; and sharing with the research community will be established by the TCTC PD/PI and approved by the TC Program Director, consistent with achieving the goals of the program and applicable NIH policies and all participants must adhere to these terms as a condition of award.
• Upon completion or termination of the research project(s), the 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 TC Program Director.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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.

This initiative is not subject to intergovernmental review.

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.

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 [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Do the investigators demonstrate the ability to work effectively as part of a multi-disciplinary team through significant prior experience in coordinating collaborative scientific research, including coordinating scientific aspects of several concurrent projects? Does the applicant demonstrate significant experience coordinating complex research efforts, including logistical support for meetings and calls, data management systems, and the development and archiving of reports and other documents? Does the applicant demonstrate significant experience in development of web sites for research programs, and in communication of research results to other scientists?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? 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 children, justified in terms of the scientific goals and research strategy proposed? Have the investigators demonstrated that appropriate goals and timelines are 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?

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 arrangements? Is there convincing evidence that applicants have infrastructure in place to immediately begin 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?

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.

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.

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.

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.

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.

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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).

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).

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.

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

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

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.

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.

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.

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.
• Ensure that all 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.
• Analyze, publish and/or publicly release and disseminate 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 TCTC-affiliated staff, participate in a cooperative and interactive manner with NIH staff, TC investigators and one another.
• Share 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.
• Work 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.
• Ensure that for activities undertaken by the 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.
• Ensure that the research is conducted in accordance with processes and goals as delineated in this Funding Opportunity Announcement.
• Upon completion or termination of the TCTC project, ensure 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.

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 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).
• Engage the CAN RB to provide feedback to the NCATS on 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.
• Work with Science Officer(s) from the trans-NIH TC Project Team, to review the scientific progress and administrative accomplishments of the 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 TCTC 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 TCTC
• Provide advice on project management and technical performance.
• Coordinate and manage 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 TCTC activities.
• The NIH reserves the right to curtail or phase out the 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 TCTC Program Director in carrying out the goals and aims of the approved studies.

Areas of Joint Responsibility include:

• Through the 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 TCTC-related issues and/or activities.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee 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.

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 progress report, 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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons 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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Danilo Tagle, Ph.D.
National Center for Advancing Translational (NCATS)
Telephone: 301-594-8064
Email: [email protected]

Mohan Viswanathan, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-3012-3745
Email: [email protected]

Tina Fleming
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0850
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.