Part 1. Overview Information

Key Dates

It is critical that applicants follow the Multi-Project (M) 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) aims to accelerate the translational use of Microphysiological Systems (MPS) in drug development by funding Centers that will establish MPS that are fit-for-purpose for industry needs and have specific defined contexts of use (CoU) and will be developed with consideration of applicable expectations to achieve qualification for regulatory use. Specifically, the FOA will provide support to establish Translational Centers for MPS (TraCe MPS) that will work towards the regulatory qualification of several MPS platforms as drug development tools (DDTs) that, once qualified, will be made commercially available to fill unmet needs in drug development and in biomedical research. Under a partnership with the United States Food and Drug Administration (FDA), the NIH will seek input from FDA in order to support this effort with its scientific and regulatory perspective to promote innovations in MPS.

Background

More than 90% of the drugs being developed fail due to unpredicted clinical toxicity or lack of efficacy in the clinic. While current approaches using in vitro 2-D cell assays and/or in vivo animal models during pre-clinical drug development have established value to biomedical research, they also have limitations in being able to reliably predict human physiological responses to various perturbations, contributing to the high attrition rate in drug development. Microphysiological systems (MPS) hold promise to overcome some of these limitations as one of the New Approach Methodologies (NAMs).

The NIH, led by NCATS, developed the MPS or Tissue Chips for Drug Screening program (https://ncats.nih.gov/tissuechip) to address translational problems in drug development through a series of proof-of concept initiatives aimed at use of MPS for 1) improving safety pharmacology studies, 2) developing MPS as disease models for efficacy studies, and 3) paving the way towards precision medicine using MPS to inform clinical studies and trial designs. The initial MPS program was a five-year partnership among NIH, DARPA and FDA, (RFA-RM-11-022 and RFA-RM-12-001) to support the development and integration of bioengineered multi-organ systems, and the generation of renewable human cell resources for predictive assessment of drug safety and toxicity. MPS disease models (RFA-TR-16-017) established the use of MPS to recreate disease phenotypes and test candidate therapeutics on them. More recently, RFA-TR-19-014 was aimed towards use of MPS in precision medicine to provide empirical support regarding the intervention's safety and efficacy, and the mechanism that underlies clinical benefit (i.e., evidence that the intervention engages its intended targets and leads to functional improvement, while informing of possible toxicity issues). The technology development path, including for MPS, is commonly non-linear, and many programs stop at the proof-of-concept stage. A key factor to a linear technology development pathway is to define the value proposition, to promptly transition from an R&D-only stage to the qualification phase, and finally move to optimization and scale-up for rapid adoption. Challenges, such as device standardization, detailed use cases for MPS to replace or support existing drug discovery assays, costs of implementation, and specialist skills required for model set up may impede the rapid uptake of such technologies. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability.

MPS are an emerging technology that holds the potential to increase translation, efficiency, efficacy, and safety of candidate therapeutics, and potentially become an integral part of the drug development process. For purposes of this Funding Opportunity Announcement, MPS (otherwise known as tissue chips or organs on chips) are defined as microscale cell culture platform for in vitro modeling of functional features of a specific tissue or organ of human origin by exposing cells to a microenvironment that mimics the physiological aspects important for their function or pathophysiological condition. MPS design may aim to provide and support cultured cells with physical (e.g., temperature, pH and oxygen), biochemical/electrical/mechanical cues (e.g., flow or stretch), structural/morphological conditions and recapitulate a set of specific properties that define a part of healthy or diseased organ or tissue function. The adoption of MPS into the drug development process is expected to permit humanized in vitro cell assays that predict human physiology more accurately in situations where species differences are an issue. They may also replace time-consuming and expensive animal experiments, giving patients earlier access to more effective and safer medications. An integral step in the widespread adoption and industrial use of MPS is its regulatory acceptance by the FDA and other global regulatory agencies.

Drug development tools (DDTs) are methods, materials, or measures that can potentially facilitate drug development and may include biomarkers, clinical outcome assessments, and other methods, materials, or measures that aid drug development and regulatory review. The FDA has developed a Qualification of Drug Development Tools Qualification Program (FD&C Act Section 507), which includes the Biomarker Qualification Program (BQP), Clinical Outcome Assessment, and Animal Model Qualification Program (AMQP). MPS can be considered for biomarker qualification if there is a biomarker output. In addition, the FDA recently established the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program, which is designed to expand DDT types by encouraging development of DDTs that are outside of the other qualification programs.

Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review under the FD&C Act. Qualification process evaluates the fitness of the model for a specific context-of-use (CoU), with characterization of the challenge agent(s) and exposure, primary and secondary endpoints, triggers for intervention, and key disease values to be replicated for quality assurance and control. Qualification does not encompass the use of a DDT outside the CoU specified through the qualification process.

Once qualified, a DDT may be used within the qualified CoU as part of any relevant drug or biologic Investigational New Drug Application (IND), New Drug Application (NDA) or Biologic Licensing Application (BLA) without submission of additional information to justify the use of the DDT. Qualification of a DDT is voluntary, and the use of a qualified DDT is not required for drug or biologic development. However, having qualified DDTs that can be used by multiple sponsors helps optimize drug development and evaluation. Increased public availability of qualified DDTs for specific CoUs is anticipated to benefit the public health through (1) increased availability of effective drugs, (2) earlier access to medical therapies and (3) an enhanced knowledge of the drug under development.

Leveraging Existing Research Resources:

Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. The use of MPS platforms that are fairly well-developed and validated for application to a specific context of use is strongly encouraged. The MPS models should consider end-user criteria for biomarkers and assays as defined in a series of publications (https://www.iqmps.org/publications) for each organ system. Additional resources may include and are not limited to: access to cell banks to source healthy and diseased cells with validated and reliable clinical and genotype information; and established commercial partners for subsequent scale up and commercialization of qualified MPS. Collaborations among academic researchers, clinicians and/or patient advocacy groups and industry are expected.

The Tissue Chip Consortium (The TC Consortium)

The NIH Tissue Chip for Drug Screening Program is led and managed by NCATS and utilizes expertise (organ physiology, regulatory science, stem cells, and bioengineering) from various Institutes, Centers and Offices at the NIH and the FDA. NIH interaction with the non-profit organization the IQ MPS Affiliate (https://www.iqmps.org/publications) allows for pharmaceutical companies to work with NCATS staff and Consortium investigators on context of use, marketability and obtaining potential stakeholder/end user feedback. The Consortium, which consists of these government and industry partners, along with NIH- funded investigators, holds an in-person meeting every 6 months. The Consortium plays a pivotal role in advancing the MPS technology. Award recipients from this FOA will become members of the NCATS-led TC Consortium.

Pre-Application Consultation:

Applicants are strongly encouraged to consult with NIH Scientific and Program Staff early in the planning of an application, i.e., more than two months before the application due date (see NIH Program contacts below). This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope and goals of the project, and intent of this FOA.

Research Objectives and Scope

The goal of this FOA is to establish a network of Translational Centers for Microphysiological Systems (TraCe MPS) that will work in coordination with the NIH and industry, with input from the FDA, towards further development and widespread utilization of MPS for specific context-of-use (CoU) applications necessary for qualification as drug development tools (DDT). TraCe MPS will be awarded as U2C Centers in order to translate MPS for industrial and regulatory use. Centers will co-develop study designs for each organ system/MPS model that will be suited to have CoU applications in one or more of the following: 1) safety pharmacology/toxicology, 2) disease modeling and efficacy studies, or 3) precision medicine, each of which could be the basis for qualification as a DDT through the FDA's established regulatory pathways. Centers funded through the U2C cooperative agreement mechanism will develop and support MPS and biological materials resources that will be made available, upon qualification, to all qualified investigators without regard to the scientific disciplines or disease orientations of their research activities. In addition to having robust study designs for qualification of MPS platforms, it is expected that sustainability planning includes developing identified avenues for eventual scale up and manufacturing of MPS as DDTs.

TraCe MPS will be supported by NCATS and NIH participating institutes and centers over 5 years of award. These participating agencies are envisioned to take programmatic and scientific stewardship of the Translational Centers. No plans are envisioned for the renewal of these centers after the initial support period.

Overall Organization of TraCe MPS

Organization: Each Translational Center will consist of a multidisciplinary research team of investigators with complementary expertise in using MPS platforms for pre-clinical applications and qualification as DDTs.

Utilizing the U2C Cooperative Agreement mechanism, each Translational Center will consist of four components: an Administration Section; an MPS Resources Section; and an MPS Qualification Section and an overall, as described below:

The Administration Section will manage and coordinate the Center’s research activities between sections, other program components, and NIH program staff, and will have oversight for integrating all sets of data generated by each of the sections consistently.

The MPS Resources Section will be responsible for ensuring standards, authentication and best practices are followed for resources such as robust and reliable cell sources, MPS hardware, and instrumentation. The MPS Resources Section should ensure that each system considers stated end-user requirements for biomarkers and assays as defined in a series of publications (https://www.iqmps.org/publications) for each organ system. It will also be responsible for establishing commercial partnerships for subsequent scale up and commercialization of qualified MPS. The MPS Resources Section may also seek collaborations with other academic researchers, clinicians and/or patient advocacy groups and industry as needed for the project.

The MPS Qualification Section will be responsible intaking and assembling data and other documentation required for submitting a qualification package to the FDA (see https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs). The MPS Qualification Section should demonstrate appropriate expertise, facilities and capability to undertake regulatory qualification of MPS.

A TraCe MPS Director [Program Director/Principal Investigator (PD/PI)] will be responsible for scientific and administrative oversight of the four components of the Translational Center. The PD/PI (the contact PIs if a multi-PI application) must devote at least 1.2 person months (10%) of full-time calendar month effort to the program.

TraCe MPS Formation and Governance

The awards funded under this FOA will be cooperative agreements (see Section VI. 2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH, with appropriate interactions with the FDA as facilitated by NIH, will be required to ensure successful execution of the projects proposed with each Translational Center.

TraCe MPS Steering Committee: A Scientific Steering Committee will be established post-award and will serve as the operational governing board. The TraCe MPS Steering Committee will meet virtually every month or in conjunction with semi-annual and annual TC Consortium meetings. It should include: the contact PD(s)/PI(s) for each award, the NIH Program Official for each award, a designated FDA representative, and external scientists (as the need arises). Key co-investigators and pre- and post-doctoral trainees, in addition to the PD(s)/PI(s), are eligible to attend TraCe MPS Steering Committee meetings. The Steering Committee may establish subcommittees, working groups, etc., to facilitate development, implementation and monitoring of specific functions, functional evaluation, result assessment, collection of information and dissemination of the data.

U2C Milestones

All projects must be milestone-driven with clear go/no-go criteria. Milestones are deliverables with quantifiable success metrics for each specific aim of the project and include, at the minimum, annual and/or intermediate quantitative criteria with key success metrics specifically defined. Each TraCe MPS award is expected to have yearly milestones for the overall and for each individual component over the course of the five-year award indicating qualification of at least 4-5 MPS platforms as DDTs, engagement with the NIH and industry partners, and plans for dissemination and/or commercialization of the qualified MPS. Prior to funding an application, the NCATS Program Official will contact the applicant to discuss the proposed milestones and any changes recommended by peer review and additional feedback from NIH and FDA staff. The NCATS Program Official and the applicant will negotiate and agree on a final set of approved milestones that will be specified in the Notice of Award. Achievement of the current year milestones as indicated in the annual report will be the basis for evaluating the successful completion and release of funds for the following award year. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, the project does not meet any of the the milestones, funding for the project may be discontinued or restricted.

Data Sharing

Award recipients are expected to share data through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center https://mps.csb.pitt.edu/. The NIH requires that datasets and associated data will be widely shared with the scientific community for research, while carefully observing established standards. Award recipients are required to comply with the NIH Data Sharing Policy (https://grants.nih.gov/grants/policy/data_sharing/). Information is expected to be shared with the TC Consortium, presented at national meetings, and published in the scientific literature.

The research interests and priorities of the participating NIH Institutes/Centers (ICs) include:

NCATS

The National Center for Advancing Translational Sciences (NCATS) is interested in qualification of MPS platforms as DDTs in many areas of drug development that include safety pharmacology assessments that measure drug toxicity, biodistribution and/or pharmacokinetics and pharmacodynamics; in the use of MPS for disease modeling and efficacy studies, such as for clinical studies of rare diseases and/or pediatric patient populations, and other human conditions for which animal models do not exist or are hard to generate; and in the use of MPS in precision medicine that will address issues of pharmacokinetic variability or difficulties of setting pharmacodynamic endpoints for patient populations. NCATS intends to commit $4M per year to fund 2-4 awards. Budget requests can be from $500,000 to $1,000,000 direct costs per year and must be strongly justified, including additional MPS platforms to be qualified.

Research interests and priorities of NCI:

The National Cancer Institute (NCI) is interested in qualification of MPS platforms as DDTs for cancer therapeutic agents to be used in studies that include efficacy, toxicity and off-target effects of anti-cancer agents; that elucidate mechanisms of action and drug resistance to cancer therapeutic agents; studies of treatments/agents that may decrease or reverse adverse cancer therapy effects or sensitize tumors to specific treatments; and agents that alter the relationship between the tumor and its host by modifying the host’s biological response to tumor cells with resultant therapeutic benefits. For MPS platforms that employ tumor cells, the DDTs can be qualified for tumors at primary and/or metastatic sites.

Research interests and priorities of NIA:

The National Institute on Aging (NIA) is interested in the development of Microphysiological Systems (MPS) as tools to advance precision medicine for Alzheimer’s disease (AD) and Alzheimer’s disease Related Dementias (ADRD) Treatment and Prevention. The development of MPS platforms that precisely model AD/ADRD will require overcoming several technical and regulatory challenges including engineering platforms that: 1) recapitulate the complexity of the human brain; 2) recreate the neurodegenerative microenvironment, 3) reflect the heterogeneity and complexity of the disease; 4) accurately predict therapy efficacy and safety in humans; 5) follow rigorous and reproducible standards; and 6) achieve regulatory approval as qualified Drug Development Tools. Applicants are encouraged to align the MPS platforms with the human multi-omic data from NIA’s Accelerating Medicines Partnership-Alzheimer’s Disease Program (AMP-AD). The AMP-AD Program supports integrated analyses of large-scale AD/ADRD molecular data with network modeling approaches and experimental validation. All data, including biological data and analytical methodology, are publicly available through the centralized big data infrastructure AD Knowledge Portal. NIA intends to commit $3.5M in FY24 to fund 2 awards. Budget requests can be up to $1,000,000 direct costs per year and must be strongly justified, including additional MPS platforms to be qualified.

Non-Responsive Applications

The following types of research activities are outside the scope of this FOA and will be considered non-responsive. (Non-responsive applications will not be reviewed.):

• Projects that propose to use MPS platforms that have not been well validated
• Projects that propose the use of MPS platforms without clearly defined specific context of use

Note: NIH will hold a pre-application technical assistance webinar for this FOA. When published, the related Notice will be linked with the FOA.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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.

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

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

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

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

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

The PD/PI (the contact PIs if a multi-PI application) must devote at least 1.2 person months (10%) of full-time calendar month effort to the program.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Nakia Brown, Ph.D.
Telephone: 301-827-3484
Email: [email protected]

Page Limitations

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

Overall Component

When preparing your application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

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

The applicant is required to provide detailed information and timelines for completing all proposed activities according to the specific aims. Applicants must include specific yearly milestones that will need to be met in order to accomplish the work set out in a five-year period. Include specific go/no-go criteria (e.g yearly) upon which project progress will be assessed for continued funding. Provide a graphical display summarizing the milestones plan in the form of a Gantt Chart. Milestones should reflect the FDA qualification process as indicated in https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-process-drug-development-tools-guidance-industry-and-fda-staff. Milestones that reflect progress in each specific aim should be easily measurable and realistic.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:

State specific aims for the TraCe MPS and how they support the overall objectives of this research program. Provide a succinct description of how the proposed work will meet the overall scientific goals of qualification of MPS and the expected outcomes and impact should those goals be achieved. The specific aims should support the purpose of serving the biomedical research community through the regulatory qualification of MPS platforms for specific context-of-use applications in drug development.

Research Strategy:

Provide an overview of TraCe MPS structure along with a concise overall vision and plan for the proposed Translational Center. This section should describe the framework for the Translational Center, overall strategy and how it will address the objectives of the program, including the broad impacts that the results of the proposed Center will have in drug development. Describe the overall study design, development and qualification process for each of the proposed MPS platforms and their intended contexts-of-use as the basis for regulatory qualification as a drug development tool. The additional specific items to be addressed in this section include but are not limited to the following:

- The application should describe the organization of the proposed TraCe MPS and its management structure, including integration of the components to maintain efficient operation and the reporting relationships of the key personnel.

- The methodology and SOPs should be described in detail, including positive and negative controls, comparator studies with current gold standards in drug development to ensure that the results of the qualification studies will be interpretable and will allow valid conclusions about the effectiveness, robustness and reliability of the MPS model for the specific context-of-use.

- Describe general approaches to be used for evaluating the context for which the MPS platforms will be qualified in the areas of i) safety pharmacology; ii) disease modeling and efficacy evaluation; iii) precision medicine.

- The overall description should demonstrate how the Translational Center will include the necessary group expertise to support the team science environment needed to complete the proposed transdisciplinary work. The statement should be brief and avoid duplicating details of the experience and expertise that are provided in the description of specific components as well as in biosketches. The TraCe MPS PD/PI (contact PD/PI for applications with multiple PDs/PIs) must be a scientist experienced in managing large complex projects.

- Milestones. Present specific yearly milestones that will need to be met in order to accomplish the work set out in a five-year period. Include specific go/no-go criteria (e.g yearly) upon which project progress will be assessed for continued funding. Provide a graphical display summarizing the milestones plan in the form of a Gantt Chart. Milestones should reflect the FDA qualification process as indicated in https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-process-drug-development-tools-guidance-industry-and-fda-staff.

- Provide detailed plans on the workflow between the Administration Section, MPS Resources Section and MPS Qualification Section, and how the planned interactions with the NCATS center hub will be coordinated.

- Provide an overview of how the MPS platforms models, once qualified from this project i) will be made available rapidly and efficiently to the biomedical research community; and ii) would serve the needs of investigators in a variety of research areas, including in drug development.

Letters of Support:

Statements of Institutional Commitment, Letters of Support from the past and potential future users of the resources and services, Letters of Collaborations, and other similar documents, if appropriate, should be included in this attachment (rather than in the Core and Project Sections).

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.

The following modifications also apply:

• While a Data Management and Sharing Plan will not be evaluated at time of review, all applications must include a Data Management and Sharing Plan. The plan should consider data sharing through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center.
• Resource Sharing Plans are expected and should indicate the plans to widely disseminate and commercialize the qualified MPS platforms.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be 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 within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administration Section

When preparing your application, use Component Type Administrative Core

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package. The PD/PI (one of the PD/PIs if a multi-PI application) efforts across all components must total at least 1.2 calendar months (10%) of full-time professional effort to the program. There will be two annual in-person TC Consortium meetings in the Washington, DC area. PD/PIs for the Administrative Section must include travel to attend such meetings in their budgets.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administration Core)

Specific Aims: State concisely the goals and objectives of the proposed Scientific and Administration Section.

Research Strategy: Applicants must address each of the following key areas:

1. Administrative Structure. Describe the proposed administrative structure of the project, including PD(s)/PI(s), key personnel, an Executive Committee, MPS Resources Section and MPS Qualification Section.

2. Scientific Expertise. Explain how the scientific expertise of the project staff (including state-of-the-art MPS technology, 3D cell culture, molecular, biochemical, physiological, stem cells, and regulatory science knowledge) will facilitate the project goals. Describe the experience of project staff to interact with regulators, clinicians, researchers and other stakeholders/end users. Explain how the expertise of staff in statistics, bioinformatics and data sharing is well-matched to the project plan. Describe, where appropriate, the team's expertise deriving and growing iPSCs for use in MPS platforms.

3. Executive Committee. An internal Executive Committee is required. Describe the composition of the committee; the roles, responsibilities, and expertise of committee members; and the frequency of committee meetings.

4. Management and Integration. Describe the management plan for the proposed project in the context of the overall organization of the proposed research resource. Describe how the management plan will facilitate the research resource goals and milestones. Describe appropriate structures that would oversee staffing, coordination with the MPS Resources Section and MPS Qualification Section, as well as regular communication with NIH, FDA and industry partners. Describe how integration of research resource components will form an efficient pipeline with the MPS Qualification Section towards the development and qualification of various MPS platforms and to their distribution/commercialization to biomedical researchers. Describe procedures for reporting and evaluation of progress and communication strategies to manage and track progress of the multiple MPS projects that make up the TraCe MPS. Describe how collaborations or subcontracts, if proposed, will be managed. Describe how the management plan will facilitate and maintain communication with NIH and FDA staff in the qualification process for MPS. The Administration Section should coordinate activities within the TraCe MPS, including progress reports and potential site visits, and should provide additional communication and materials to the NIH and FDA as needed.

5. Sustainability Planning. Describe the long-term plans for achieving sustainable community access to the qualified MPS platforms including plans for commercialization. Sustainability in the context of this resource refers to continuing, long-term access to the resource without NIH continued support.

Letters of Support:

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.

While a Data Management and Sharing Plan will not be evaluated at time of review, all applications must include a Data Management and Sharing Plan. The plan should consider data sharing through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

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

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

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

MPS Resources Section

When preparing your application in ASSIST, use Component Type MPS Resources Section.

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

SF424 (R&R) Cover (MPS Resources Section)

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant’s Project

Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Resources Section)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (MPS Resources Section)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (MPS Resources Section)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (MPS Resources Section)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (MPS Resources Section)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (MPS Resources Section)

Specific Aims: State concisely the goals of the proposed MPS Resources Section and summarize the expected outcome(s) and impact that the results of the proposed Resource Section will exert on the ability of biomedical researchers at research centers, academic and industrial institutions, the NIH, and other federal agencies to use MPS qualified as DDTs for specific contexts-of-use and their broader impact to the scientific community.

Research Strategy: State concisely the goals of the proposed MPS Resources Section and summarize the expected outcome(s), including the impact that the results of the proposed MPS Resources Section will exert towards standardization, authentication, robustness and reproducibility of resources that are needed for the various MPS platforms to evaluate their suitability and effectiveness as a qualified DDT, and increase confidence towards regulatory qualification. Describe mechanisms to ensure internal quality control of ongoing Section activities. Describe the roles and responsibilities of the PD/PI(s) involved in the MPS Resources Section, the organization of the resources, including collaborators, interactions with Administration Section, Executive committee, provision of research and services to the MPS Qualification Section, and indicate how they contribute to reach the overarching goals of TraCe MPS. Describe the features of the institutional environment that are relevant to the effective progress of the proposed program. As appropriate, describe available resources, such as laboratory facilities, participating and affiliated units, geographical distribution of space and personnel, and consultative resources.

Provide information on the support and commitment of the parent institution for the resources.

Describe a plan to document the SOPs, best practices on the evaluation of quality and suitability of the resources for each MPS platform in consideration for qualification.

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:

While a Data Management and Sharing Plan will not be evaluated at time of review, all applications must include a Data Management and Sharing Plan. The plan should consider data sharing through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center.

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

PHS Human Subjects and Clinical Trials Information (MPS Resources Section)

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

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

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

MPS Qualification Section When preparing your application in ASSIST, use Component Type MPS Qualification Section.

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

SF424 (R&R) Cover (MPS Qualification Section)

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant’s Project

Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (MPS Qualification Section)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (MPS Qualification Section)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (MPS Qualification Section)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (MPS Qualification Section)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (MPS Qualification Section)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (MPS Qualification Section)

Specific Aims: State concisely the goals of the proposed MPS Qualification Section and summarize the expected outcome(s), including the impact that the results of the proposed MPS Qualification Section will exert on improving the value and suitability of the various MPS models being proposed for qualification, their "fit for purpose" metrics, and the specific context-of-use for each model (minimum of 4-5 MPS platforms each with a specified and distinct context-of-use, to be qualified over the 5 year funded period).

Research Strategy: Describe what MPS platforms are being proposed for qualification and for what context-of-use. Describe in detail the characteristics of the models that make it fit for purpose. Describe in detail the study design for qualification as DDT, how the assays will be conducted, and how this innovative research will impact and improve the translational center's activity (i.e., generate new information, services, products, or provision of MPS models). The additional specific items to be addressed in this section include but are not limited to the following:

- Provide preliminary or published data, if available, that support using the approaches to be used.

- Describe in detail functional assays and SOPs for evaluation of MPS platforms in specific context-of use settings, including evidence of experience with the relevant techniques e.g. immunohistochemistry, fluorescence microscopy, DNA or RNA sequencing, etc.

- Describe in detail plans for each MPS platform being proposed for qualification as DDT, plans to interact with the NCATS center hub, and appropriate timelines.

- Describe plans for the collaboration with other components of the Translational Center, to design and improve the whole TraCe MPS network operation and implementation of protocols.

- Define what data will be collected, how it will be analyzed and provided to the MPS Database Center and at what frequency.

- Provide additional experimental details and methods to validate the results and alternative strategies if not successful at first.

- Indicate the TraCe MPS capacity, how many MPS platforms will be tested and analyzed for qualification in a specific time frame.

- Describe plans to increase the rigor and reproducibility of the outcomes (see: https://www.nih.gov/research-training/rigor-reproducibility) whenever appropriate for the model or system being studied; describe approaches, if available, for analyzing potential sex differences.

- Provide a timeline in the form of a Gantt chart and the set of milestones for the MPS Qualification section that quantitatively measures progress towards each of the proposed specific aims.

Resource Sharing Plan:

While a Data Management and Sharing Plan will not be evaluated at time of review, all applications must include a Data Management and Sharing Plan. The plan should consider data sharing through the NCATS-supported Microphysiological Systems Database Center at the University of Pittsburgh Drug Discovery Center.

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

PHS Human Subjects and Clinical Trials Information (MPS Qualification Section)

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

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

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

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

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

4. Submission Dates and Times

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at {[email protected]} when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

The U2C application is a multicomponent application, with an "Overall" component that is the aggregate of the Administration, MPS Resource and the MPS Qualification Sections. During the review process, reviewers will first consider each of the review criteria listed for each of the Sections and provide an adjectival descriptor (Administration Section) or overall impact score (MPS Resource and Qualification Sections) for each component. After the evaluations of the individual Sections are completed, the Overall application will be evaluated and an Overall impact score assigned to the application.

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

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

Significance

Does the proposed MPS platform(s) for qualification address an important problem or a critical barrier to progress in the field?Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

Does the proposed Center address the needs of the research programs 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 program? Does the proposed Center address the needs of the drug development and research community that it will serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims strengthen the Center and the value of MPS as New Approach Methodologies (NAMs) and as DDTs?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

Are the necessary expertise present to support the team science environment needed to complete the proposed multidisciplinary work? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing large complex research centers? Do the investigators demonstrate significant experience with coordinating collaborative translational research? Does the applicant have experience overseeing selection and management of subawards, if needed? Do they have appropriate experience and expertise to accomplish the overarching goals of the Center? Have they demonstrated a record of accomplishments managing related, comparable or similar resource? Do the investigators demonstrate significant expertise to evaluate and qualify the appropriate MPS models that are fit for purpose related to the specific context-of-use?

Innovation

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

Specific to this FOA:

Are the proposed MPS platforms likely to have an significant impact in drug development and biomedical research? Is there evidence that MPS models will be qualified and adopted as appropriate to assure advances in NAMs and promoting new DDTs, and to assure that relevant information about MPS models will be easily accessible by biomedical researchers? Is there a high likelihood that the activities proposed will be nimble enough to stay current to the greatest extent possible, given rapid advances in the MPS field?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA:

Does the Milestone Plan for the overall and individual components include appropriate milestones that will need to be met to accomplish the work set out above in a five-year time frame? Do the study design and operating plan provide an opportunity for collaboration, integration, and interaction within the Center and with NIH and FDA? Does the approach enable identification of risks and deficiencies of the proposed MPS tools compared with the current standards, e.g., whole animal models or entire human tissues or organs? And how will they be addressed or supplemented by additional experiments or studies?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific 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?

Specific to this FOA: Is there evidence that the environment is conducive to operating a Center of the complexity and scope of the TraCe MPS?

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.

The Administration Section will receive a merit descriptor (outstanding, acceptable, unacceptable) for the following:

- Is the proposed administrative structure likely to function effectively in achieving the aims of the Center? Is the management plan well integrated and likely to facilitate achieving section goals and objectives?

- Is there evidence that the scientific staff will interact productively with the Administration Section and other components of the program, the NIH and the FDA?

- Are plans to evaluate the progress across the Center, communication management strategies and progress tracking of the multiple projects that make up the TraCe MPS adequate?

- Are details for the Administration Section activities to coordinate participation in evaluation activities, including progress reports, site visits and additional communication materials to the NIH and FDA described?

- Are plans for composition and use of Executive Committee in operation of the Center likely to aid in achieving TraCe MPS goals and objectives?

Review Criteria for the MPS Resources Section

Reviewers will consider each of the review criteria below in the determination of scientific merit, and provide an overall impact score for the MPS Resources Section. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

- Are the goals and administrative structure proposed in the MPS Resources Section adequately described?

- Does the proposed administrative structure function to support and maintain the resource needs of the Center for the specified MPS platform proposed for qualification?

- Does the Section Lead have the expertise and the administrative leadership experience to achieve the overarching goals of the MPS Resources Section?

- Does the applicant/organization have a demonstrated track record of running an established center that includes recognized expertise, knowledge of managing such a resource, and appropriate expertise on the specified MPS platform(s)?

- Are the different aspects of the resource adequately described?

- Does the MPS Resource Section utilize state of the art technologies and resources to improve the design and qualification of the MPS models?

- Does the application address evaluation of operational mechanisms, a continuous process to improve programs, and implementation of improvement plans of the resource's procedures and programs?

Review Criteria for the MPS Qualification Section

Reviewers will consider each of the review criteria below in the determination of scientific merit and provide an overall impact score for the MPS Qualification Section. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

- Are there detailed plans describing the proposed research and how this will enhance the Center goals and activities?

- Will the proposed research likely to lead to the qualification and community adoption of MPS platform(s)?

- Are the validation plans (analytical and clinical) appropriate for the proposed research?

- Are the research projects adequately developed and appropriate to improve and support the methods and technologies used to evaluate and qualify the MPS models?

- How sound is the scientific rationale for the MPS Qualification Section to leverage the MPS Resources Section?

- Will the biomedical community benefit from the research projects being proposed?

- Will the proposed MPS platform, research protocols and results be accessible to the research community?

- Are the plans for functional assays and SOPs for evaluation of MPS models in specific context-of-use described adequately to achieve the goals? Does the application include evidence of experience with the relevant techniques?

- Do the plans for the development of functional assays and SOPs for the tests allow conduct of comparative analysis of the MPS platforms with current "gold standards"?

- Are plans adequate for collaboration with other components of the program and sufficient to design and improve the whole network operations and implement protocols?

- Are experimental details and methods to validate the results and alternative strategies, if not successful at first, presented?

- Are plans described to increase the rigor and reproducibility of the outcomes and approaches?

- Are a timeline and milestones provided and reasonable?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

Applications may undergo a 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.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

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

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

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

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

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

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

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

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

The 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, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

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

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

• Defining the details and goals of the project within the guidelines of this FOA.
• Determining experimental approaches, designing protocols, settling on project milestones and conducting experiments Adhering to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity
• Submitting quarterly progress reports.
• Accepting and implementing any other common guidelines and procedures developed for the TraCe MPS program and approved by the trans-NIH Tissue Chips Project Team
• Fully participating in the highly collaborative NIH Tissue Chips Consortium.
• Managing all data acquired and making those available to the public through the Microphysiological Systems Database Center funded by NCATS at the University of Pittsburgh and will be available to government and private partner.
• Coordinating, cooperating, and participating with NIH and FDA staff in the scientific, technical, and administrative management.
• Identifying and maintaining infrastructure and collaborations needed to support the development of the proposed MPS models for qualification.
• When needed, working with private partners to acquire and maintain needed resources for the projects.
• Working with the NIH, FDA and industry partners to establish context of use, standardization and qualification approaches.
• Performing established standardization and benchmarking milestones.
• Ensuring that all affiliated staff will maintain the confidentiality of the information developed by the investigations, including, without limitation, informatics tools, protocols, data analysis, conclusions, etc. per policies approved by the TC consortium as well as any confidential information received by third party collaborators.
• Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the FOA.
• Participating in a cooperative and interactive manner with NIH and FDA staff, and other TraCe MPS recipients.
• 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 TraCe MPS program.
• Working with the members of TC Consortium to establish agreements that address the following issues: (1) adherence to data sharing policy as approved by Program staff prior to award. Data sharing with Tissue Chips consortium members and data sharing with industry partners, as appropriate; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the TC 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 TC consortium members that operationalizes material transfer in an efficient and expeditious manner as appropriate and consistent with achieving the goals of the program; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• Ensuring that for activities that involve academic and/or industry collaborations within and outside the TC Consortium there are appropriate research collaboration agreements (e.g., CRA, CDA, MTA etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement terms of award as well as any additional applicable NIH policies and procedures.
• Ensuring that the research is conducted in accordance with processes and goals as delineated in this FOA.
• Upon completion or termination of the project, ensuring all study materials, tools, databases and procedures developed from the project are broadly available (e.g., putting into the public domain) or made accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research. The data sharing plan should include a plan to accomplish this at end of the study according to the new NIH data sharing plan effective January 25, 2023.

Publications and Communication Plans:

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

The Principal Investigator(s) will be responsible for:

• Participating in regular (monthly) conference calls with all NIH and FDA Project Team members.
• Coordinating efforts with other recipients, especially in circumstances where synergy of efforts and resources is beneficial to the overall goals of the TraCe MPS program.
• Participating and presenting findings at the semi-annual Tissue Chips Consortium meeting convened by the NIH and FDA.
• Coordinating or jointly publishing findings in a timely manner, and as to have the broadest impact.
• Making new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH.

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

• NCATS and participating ICs 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).
• NIH Tissue Chip Project Scientists are members of the trans-NIH Microphysiological Systems Working Group that will have substantial scientific/programmatic involvement in the technical assistance, advice and coordination of this team; the NIH Tissue Chip Project Scientists will facilitate and not direct the activities of the team. Specifically, the NIH Tissue Chip Project Scientists will be substantially involved in this project as follows:
• The Program Officer will coordinate and facilitate the activities of the program, attend and participate in all meetings of the TC Consortium.
• The Program Officer will work with Project Scientists from the trans-NIH Microphysiological Systems Working Group to review the scientific progress and administrative accomplishments of the award, recipients and review the project for compliance with operating policies and procedures, including meeting milestones. 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. The review of scientific progress will be shared with the assigned Program Officer. 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.
• The Program Officer will prepare up-to-date summaries of program accomplishments based on manuscripts provided by the recipient within two weeks of acceptance for publication.
• The Program Officer will participate (with the other trans-NIH Microphysiological Systems Working Group members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted.
• The Program Officer will serve as a liaison between the award recipients, the Advisory Councils for those Institutes that plan to administer elements of the NIH Tissue Chips program, and the larger scientific community.
• The Program Officer will coordinate the efforts of the recipient with others engaged in MPS research, including other recipients under this FOA and those award recipients involved in related NIH programs.
• The Program Officer will attend all trans-NIH Microphysiological Systems Working Group meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• The Program Officer will periodically report progress to the Directors of NIH Institutes/Centers/Offices involved in the NIH Tissue Chip program.

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• The Program Officer will ensure that the awarded project(s) adhere to cooperative agreement data-sharing and other resource-sharing policies.
• The Program Officer will facilitate collaborations with and access to other NIH-supported research resources and services.
• The Program Officer will facilitate negotiations with companies interested in working with the award recipients.
• The Program Officer will provide guidance to the award recipients on private-public partnerships and regulatory agency policies.
• The Program Officer will invite experts with relevant scientific expertise to provide feedback on TC program activities.
• The NCATS Program Officer will coordinate and manage trans-NIH Microphysiological Systems Working Group efforts.
• The Program Officer and Project Scientists will lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the award recipient institutions who are to serve as External Scientific Consultants, as needed.

• The Program Officer and Projects Scientists will provide input into the design of research activities and play a key role in coordinating research efforts.
• The Program Officer and Projects Scientists will monitor progress on the agreed upon milestones and help identify recourses if needed.

• The Program Officer and Projects Scientists will provide advice on project management and technical performance.

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

Areas of Joint Responsibility include:

• Collectively, award recipient and the Program Officer/Project Scientist(s) will determine criteria and processes for quality control of information and data to be posted for the research community, consistent with NIH policies and achieving the goals of the program as described in this Funding Opportunity Announcement.
• Negotiate and agree on a final set of approved milestones.
• Participate in recurring monthly meetings to discuss progress, obstacles and any other TC-related issues and/or activities.
• The NIH will enlist additional scientific experts as necessary from within the NIH, other government agencies, such as the FDA, and from industry partners, such as the IQ Consortium MPS Affiliate, whose function will be to assist the Program Director in carrying out the goals and aims of the approved studies.

Data

Recipients will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Intellectual Property

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

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

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

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

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

Dispute Resolution:

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

3. Data Management and Sharing

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

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

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

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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

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

Brian Sorg, Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-276-5712
Email: [email protected]

Zane Martin, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-7130
Email: [email protected]?

Nakia Brown, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-3484
Email: [email protected]

Steve Eisberg
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0528
Email: [email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Jeni Smits
National Institute on Aging (NIA)
Phone: none
E-mail: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.