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.

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

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 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 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 (TCTCs) were established to investigate replicability of tissue chip technology and to promote adoption by the research community by validating tissue chip platforms. A companion FOA seeks to provide additional support to these testing centers (see RFA-TR-18-006) and successful MPS DC applicants are expected to work closely with NextGen TCTC awardees.

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to invite new and renewal cooperative agreement applications for the Tissue Chip Testing Center (TCTC) Microphysiological Systems (MPS) Data Center (MPS DC), which supports the NIH Tissue Chip Consortium. The Consortium facilitates the development, validation and dissemination of tissue chip (TC) technology through support for collaborative research in 1) development of tissue chips for toxicity and safety testing of promising therapeutics (RFA-RM-11-022); 2) development of tissue chips for disease modeling and efficacy testing (RFA-TR-16-017 and RFA-TR-16-019); and 3) independent validation of tissue chip platforms through the TCTCs (RFA-TR-16-006). The MPS Data center is expected to be the central clearinghouse for TC data management, and will incorporate novel approaches and technologies for data management, data mining, and data sharing across many organs and tissues, diseases, data types, and TC platforms. The MPS Data center is expected to provide different levels of public and tiered access to TC information for basic and clinical researchers, academic and practicing physicians, the pharmaceutical industry, NIH, FDA and other government agencies, patients, and the lay public. The MPS Data Center will develop and make available a secure, customizable coordinated data management system for collection, storage, and analyses of diverse data types from multiple TC platforms being developed and used for drug screening, safety and efficacy testing.

The MPS DC should develop and provide a user-friendly system for data mining, and a portal for access and integration of publicly available data resources. The MPS DC should have computational sophistication for scaling the systems and tools to allow incorporation of many different data types. The MPS DC must address confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing. It will work with the TC developers, NextGen TCTCs, NIH, FDA, International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) and other stakeholders to facilitate data collection and standardization, analyses, and distribution. While NIH-funded Tissue Chip programs are active, the MPS DC will serve as a central data collection, analysis and sharing site, with the vision that it will continue to exist beyond the end of the programs as a critical resource for the scientific community. By making use of best open science practices and working closely with the TC Consortium and the broader scientific community, it is envisioned that the MPS DC will evolve into an extensible and sustainable resource.

Structure of the Tissue Chip Consortium (The TC Consortium)

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.

MPS Data Center

The MPS DC will work directly with the Tissue Chip Consortium, composed of tissue chip technology developers, tissue chip testing centers, government officials, industry representatives and other potential stakeholders. The MPS DC will be milestone-driven, and actively work with the TC Consortium and TC developers to facilitate data collection and standardization, and analysis and distribution of data and 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) provide the framework for partnership between the TC Developer and TCTC PD/PI. TCTCs work with their institutional technology transfer or sponsored research office regarding the terms and conditions of the CDA and CRA with the TC Developers. The MPS DC will be expected to complete a CDA and CRA with partners contributing data to the MPS DC.

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 MPS DC investigators make modifications of TC platforms that significantly change performance and/or function, both parties are expected to discuss ownership interests where applicable and as specified in 37 CFR 401, 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 MPS DC 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 MPS DC 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 MPS DC investigators.

Data/Information Ownership and Disclosure: MPS DC 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 MPS DC PD/PI’s do not publicly disclose confidential 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.

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

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).

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.

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.

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: [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 manage data resulting from all studies without delay.

Document any unique features of institutional support and availability of resources to allow expansion of MPS DC activities to accommodate growth of the TC Consortium.

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

Applicants should document experience and knowledge of the following issues in the context of data centers in the biosketches:

• Familiarity with the NIH Tissue Chip program and any prior experience in collaborating with Tissue Chip Consortium PIs, government and industry stakeholders.
• Expertise in informatics, analysis, database management, and customization of software.
• 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 with in vitro and in vivo toxicity testing.
• Prior experience/track record of interfacing with academic investigators, industry and regulatory agencies.
• Experience with 3D cell culture, iPSC lines, and other cell sources.

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

Funds should be requested to explain costs for the following categories of activities:

• Development and implementation of standardized data transfer tools for TC Consortium users.
• Development and implementation of secure, robust, user-friendly database interfaces with tiered access, including open access options.
• Development of novel approaches and technologies for data management, data mining, and data sharing across many organs and tissues, diseases, data types, and TC platforms.
• Extending the utilization of the MPS DC beyond NIH-funded activities to enhance its utility for the broader scientific community.

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 general items should be addressed by the applicant in the research strategy:

Describe the proposed data management and coordination within the TC Consortium, indicating the experience in serving as a data management center for a large multi-institution research consortium. Describe the nature of the multidisciplinary team necessary to provide the web-based, technical, and statistical resources required to maintain the MPS DC. Include plans and approaches for interacting with the TC consortium members. Specifically, address plans to work with TC investigators, government officials and industry partners to integrate data on reagents and cell sources from TC testing, including, but not limited to iPSC lines, predefined testing compounds, cellular matrices, media, etc.

• Data management for an array of chemicals and reagents needed to perform the various TC assays.
• Ability to manage data on tracking use of reagents, chemicals and tissue sources from TCTCs and TCDs.
• Ability to manage data on tracking and verify quality and control of reagents, chemicals and tissue sources from TCTCs and TCDs.
• Strategy to work with TC investigators, government officials and industry partners to collect, QC and release tiered data from assays used to test each organ system.
• Proposed data stream for information and data coming from NextGen TCTC (RFA-TR-18-006), current and former NIH awardees under the TC program.
• Applicants should outline team accomplishments, including any pilot programs or newly developed tools, and discuss their potential impact on the TC Consortium as well as the wider field. Any difficulties in achieving previously proposed specific aims should be addressed. Do not duplicate information provided on individual biosketches. Otherwise, individual expertise and accomplishments belong on biosketches

Milestones

Applicants must provide a set of milestones and timelines that demonstrate they will be able to accomplish project objectives, and generate outputs and data needed to provide a robust, secure database service for 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 data and accompanying hardware/software and cell resources information from the TCTCs and TC Developers, for example, within the first 3 months.

How informatics will be used 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 data integration from several organ platforms will be accomplished during the project period.

How a pace of continuous data integration from testing of new devices by NextGen TCTC(s) will be achieved and maintained

How plans to expand and maintain the database over the future years will be formulated, based on new initiatives from the NIH Tissue Chip program, the expanding TC Consortium, and the need for high-quality publicly available TC data sources.

Data Center Functions

To accomplish the goals of the TC for Drug Screening program, the MPS DC must serve as a core resource to the TC Consortium and be able to perform a number of functions and activities that promote the accomplishment of these goals.

MPS DC applications must document the expertise and experience in how the following functions and activities will be performed:

• Provide a secure, customizable, scalable coordinated data management system for the integration of TC data from many different TC platforms, across many diseases, and produce readouts for safety and efficacy studies on these TCs. This support should include developing and/or adapting new technologies and technological advances to facilitate data collection, storage, and management from TC Consortium members;
• Coordinate with the TC Consortium to define standards for data types, format, quality, curation, annotation, and common data elements so that data sets are mineable and comparable. Monitor adherence to those standards. Create tools to harmonize disparate data formats;
• Develop with TC Consortium PIs standard experimental metadata required to be submitted with each dataset, including common data elements, such as clinical phenotypes, using well-defined formats and associated controlled vocabularies;
• Provide a portal and tools for integration of developed and publicly available datasets for data mining;
• Provide a user-friendly resource site for the public, research scientists, and TC Consortium members that provides clear and easy management and retrieval of data and tools from the TC program and is accessible to the general scientific community across a variety of platforms;
• Provide end-user training (online resources, remote assistance, video teleconferencing), documentation, and technical support;
• Incorporate new approaches to distributed computing and federated databases;
• Incorporate new approaches to database support and data management to reduce the burden of rising costs of software;
• Address confidentiality issues and access related to database management and distributed computing and allow multiple levels of data sharing;
• Manage access permissions across collaborating TC Consortium members, the scientific community, and the public;
• Work with government staff and TC Consortium members to define and implement data and protocol validation methods, and a process to evaluate the quality of submitted data prior to Consortium use and public release;
• Provide scalable infrastructure. The TC for Drug Screening program is multi-faceted and may expand its size and scope in the future. A successful applicant must have the ability and resources to expand operations to meet such future needs;
• Keep the code and resources open source.

Readiness to Undertake Database Activities

Applicants should address the following:

• The capacity to scale up operations and the approach to doing so if the need arises.
• Documentation that MPS DC investigators have access to an array of software and specialized systems needed to perform the various data imports and analyses; 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; the ability to check data quality and correctness before release to wider circles.

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 Data Sharing Plan. This plan must include timely data release to the TC Government Officials and TC Developers as determined by the MPS DC Program Director during the course of the MPS DC 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 MPS DC 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.
• Applicants must commit to sharing and making protocols/methodologies, data, materials, models, 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 MPS DC 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 MPS DC 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:

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

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.

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

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 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).

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 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 this application provide a significant contribution to the support of the TC Consortium activities? If the aims of the application are achieved, how will the activities of the TC Consortium be advanced? What will be the effect of these efforts on the methods, technologies, or services provided to the TC Consortium?

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 applicant have a proven record of database development and integration? Does the PD/PI have experience in managing data from TC platforms? Does the MPS DC infrastructure have the ability to expand operations to meet the needs of an expanding TC Consortium?

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: Does the application develop or employ novel concepts, approaches, methodologies, tools, or technologies to facilitate data collection, storage, and management? Will this approach include developing and/or adapting new technologies and technological advances for distributed computing and federated databases?

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: Does the proposed approach provide for a secure, customizable, scalable coordinated data management system? Does the applicant adequately address confidentiality issues? Is the proposed plan appropriate for the state of knowledge, current capabilities and resources? Are adequate plans to assess limits and sensitivity of each TC system, and compare to current in vitro and in vivo gold standards described? Are there appropriate milestones that ensure timely completion of the project? 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 device data?

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?

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: Does the applicant have adequate resources at the institution to provide logistical and administrative assistance as well as operational support? Is there convincing evidence that applicants have infrastructure in place to immediately begin data import and integration of organ/TC-specific assays that fit context of use for each organ system? Is there evidence of unique features of institutional support? Are resources available from the applicant s institution to allow expansion of MPS DC activities to accommodate growth of the TC Consortium for example server space, data storage capabilities etc?

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.

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 an MPS database center.
• Working with NIH Program Officials and industry partners to establish context of use, standardizing and validating approaches.
• Managing and performing analyses on data from established standardization and validation milestones.
• Acquiring data generated by microphysiological devices from tissue chip researchers and working with them to understand the perimeters/context of use for each system.
• Ensuring that all MPS DC-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.
• Ensuring efficient data transfer to a successor (if applicable) at the end of the funding period
• Along with all MPS DC-affiliated staff, participating in a cooperative and interactive manner with 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 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 MPS DC 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 MPS DC project, ensuring all study materials, tools, databases and procedures developed by the MPS DC are broadly available (e.g., putting into the public domain) or making 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 MPS DC, 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 MPS DC, 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 MPS DC 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 MPS DC.
• Provide advice on project management and technical performance.
• Coordinate and manage TC Consortium 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 MPS DC activities.
• The NIH reserves the right to curtail or phase out the MPS DC 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 MPS DC procedures and milestones, and/or (3) substantive changes in the management of MPS DC that are not in keeping with the objectives of the FOA.
• The NIH will enlist additional technical experts as necessary from within the NIH, other government agencies, such as the FDA, and from industry partners whose function will be to assist the MPS DC Program Director in carrying out the goals and aims of the approved studies.

Areas of Joint Responsibility include:

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

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 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.

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 Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: [email protected]

Ki-Cha Flash
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0846
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.