It is critical that applicants follow the Research (R) Instructions in How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

As part of its Critical Path Initiative, FDA recognizes the need for collaborations established under the terms and conditions of a cooperative agreement, whereby existing resources and expertise can be used to the fullest extent possible. In 2009, FDA identified the Critical Path Institute (C-Path), a freestanding 501(c)(3) non-profit organization as one suitable partner in achieving its goals and awarded them a cooperative agreement to support Critical Path-related projects, mutually identified by FDA and the Critical Path Institute. FDA seeks to continue the projects that were begun and in progress under this grant.

The Critical Path Initiative is FDA's national strategy for transforming the way FDA-regulated medical products are developed, evaluated, and manufactured. The Initiative was launched in March 2004, with the release of FDA's Challenges and Opportunities Report. The publication diagnosed the reasons for the widening gap between scientific discoveries and their translation into innovative medical treatments. The report concluded that collective action was needed to modernize scientific and technical tools as well as harness information technology to evaluate and predict the safety, effectiveness, and manufacturability of medical products.

In 2006, the Critical Path Opportunities Report stated, Many of the Critical Path opportunities described in this report cannot be accomplished by one entity alone. No single company, university, or governmental agency will have sufficient resources, expertise, or information base to undertake the work. We will need to develop new ways to collaborate and share data to accomplish our common goal of a robust Critical Path infrastructure . Public-Private Partnerships convened by neutral non-profit conveners are able to bring together stakeholders from government, academia, professional societies, patient advocacy groups, and industry in the pre-competitive space to address these Critical Path needs. Through nationwide collaboration with other Federal, academic, scientific, and industry organizations, the Critical Path Initiative seeks to develop new tools to facilitate innovation in FDA-regulated product development. Examples of tools include novel biomarkers, Clinical Outcome Assessment Tools, laboratory assays, genetic tests, and state-of-the art information technologies, etc. In this initiative, FDA plays the role of a facilitator in the creation of partnerships and collaborations to support specific scientific projects.

As part of its Critical Path Initiative, FDA recognizes the need for collaborations established under the terms and conditions of a cooperative agreement, whereby existing resources and expertise can be used to the fullest extent possible. In 2009, FDA identified the Critical Path Institute (C-Path), a freestanding 501(c)(3) non-profit organization as one suitable partner in achieving its goals and awarded them a cooperative agreement to support the Critical Path Initiative-related projects, mutually identified by FDA and CPath. The Critical Path Institute was awarded this cooperative agreement again in 2014 and 2019.

The applicant must demonstrate the ability to:

1. Establish an adequate administrative and scientific infrastructure to implement all projects under this collaborative effort

2. Identify and/or hire sufficient number of qualified personnel to conduct the necessary research and project-manage all related activities, including review of project milestones for degree of completion, preparation/reporting of project findings, periodic and final reports, all for approval by FDA, and for subsequent distribution in the public domain

3. In conjunction with FDA, develop plans for the conduct of identified research projects

4. Identify and/or build, and effectively leverage databases and other facilities and/or resources for the conduct of identified projects

5. Upon completion of a given project, propose related studies/projects, if needed, to build on the findings of the project and continue to leverage established resources and personnel. In addition, the applicant must demonstrate the capability to address regulatory science issues that define FDA’s public health mission and priorities

6. Ability to coordinate a sustainability plan to obtain funding to maintain the core grant functions as well as a plan for the individual consortia/AIMs until the objectives and goals are met.

7. The applicant must also provide an assurance that it will not accept funding for a Critical Path Public-Private Partnership project from any organization that manufactures or distributes products regulated by the Food and Drug Administration unless it provides assurances in its agreement with the Food and Drug Administration that the results of the Critical Path Public-Private Partnership project will not be influenced by any source of funding.

8. Plan for data sharing

This cooperative agreement (CA) is to continue to maintain and manage existing consortia groups convened and established by the Critical Path Institute and the AIMs listed below:

AIMS:

1. Rare Disease Cures Accelerator Data Analytics Platform (RDCA-DAP)

2. CURE Drug Repurposing Collaboratory (CDRC)

3. Acute Kidney Injury (AKI) Working Group and AKI Data Acquisition

4. Alpha-1 Antitrypsin Deficiency (AATD) Pre-Consortium

5. Lysosomal Diseases (LD) Pre-Consortium

6. Critical Path for Rare Neurodegenerative Diseases (CP-RND)

AIM Descriptions and Goals/Objectives:

1. Rare Disease Cures Accelerator Data Analytics Platform (RDCA-DAP)

Description:

The Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP) was established in 2019 to provide a centralized and standardized infrastructure to support data-sharing and accelerate rare disease characterization, with the goal of accelerating the development of treatments and cures for rare diseases.

Objectives:

• RDCA-DAP promotes the sharing of existing patient-level data and encourages the standardization of new data collection. By integrating such data in a regulatory-grade format suitable for analytics, RDCA-DAP accelerates the understanding of disease progression (including sources of variability to optimize the characterization of subpopulations), clinical outcome measures and biomarkers, and facilitates the development of mathematical models of disease and innovative clinical trial designs.
• RDCA-DAP is positioned to generate solutions to drug development bottlenecks. As such, the utility of the patient-level data is maximized, and data may be used to develop tools that will be accessible to the community in order to optimize and accelerate drug development across rare diseases.

2. CURE Drug Repurposing Collaboratory (CDRC)

Description:

CURE Drug Repurposing Collaboratory (CDRC) is a public private partnership to advance the collection of real-world data (RWD) to generate real-world evidence (RWE) that can inform drug repurposing for areas of high unmet medical need. CDRC uses the CURE ID platform which is an FDA-NCATS collaboration that allows the global clinical community to report novel uses of existing drugs to treat diseases through a website, a smartphone, or other mobile device. The repository captures the clinical outcomes when drugs are used for new indications, in new populations, in new doses, or in new combinations.

Objectives:

• Leverage the Collaboratory across multiple therapeutic areas to evaluate the efficacy of existing drugs for new indications using multiple data sources, including real-world data
• Target emerging/reemerging infectious diseases, anti-microbial drug- resistant infections, neglected infectious diseases, diseases in pediatric populations and pregnant women, as well as rare diseases including oncology, where there is little financial incentive for pharmaceutical companies to develop new drugs
• Evaluate drug leads through advanced analytics to identify candidates for repurposing as new treatments in a transparent, open forum
• Inform the design of clinical trials of already marketed drugs for new indications
• Generate real-world evidence to update and inform existing disease treatment guidelines and expanding drug labels
• Develop a regulatory roadmap to advance drug repurposing through drug relabeling paths to expedite the availability of safe and effective treatments for diseases with limited or no treatment options

3. Acute Kidney Injury (AKI) Working Group and AKI Data Acquisition

Description: The Acute Kidney Injury Working Group (AKI WG) was established to optimize the collection of translational biomarker data to develop better predictive tools for kidney toxicity. The AKI WG has brought together key stakeholder groups in nephrology and the AKI patient community, thereby enabling evaluation of unmet needs in drug-induced kidney injury (DIKI), opportunities for collaboration, and identification of possible solutions for DIKI and data sharing.

Objectives: The overarching objective is to transform translational kidney safety approaches to accelerate drug development across therapeutic areas and improve patient safety during clinical trials.

• Complete and implement the action plan for development of predictive tools for use in clinical trials of novel therapies, which will feed into, synergize with, and support current and future efforts to develop tools that are needed to advance drug development for the treatment and prevention of AKI.
• Acquire additional clinical and nonclinical data on biomarkers of kidney injury for the Biomarker Data Repository (BmDR)

4. Alpha-1 Antitrypsin Deficiency (AATD) Pre-Consortium

Description: The rare disease alpha-1 antitrypsin deficiency (AATD) is characterized by chronic obstructive pulmonary disease, respiratory failure, and increased mortality, as well as hepatic disease which in the most severe cases may lead to cirrhosis, the development of hepatocellular carcinoma, and ultimately, the need for liver transplantation. The only FDA-approved products for AATD-related lung disease are augmentation therapies manufactured from human plasma. Studies suggest that augmentation therapy may slow decline in forced expiratory volume in 1 second (FEV1), and slow decline in lung density. In addition, some data suggest that a lower rate of loss of lung tissue as measured by computed tomography (CT) lung density correlates with lower mortality and need for lung transplant; however, the available studies are inconclusive. There are no approved drugs for hepatic disease.

A public-private partnership consortium launched in 2023, focused on aggregating available clinical trial data and other studies to evaluate the longitudinal performance of biomarkers, including CT lung density, and clinical measures in AATD for potential use as endpoints or surrogate endpoints to evaluate future therapies for AATD. There is an unmet need for non-invasive means to identify, stage, and monitor Pi*ZZ genotype patients at risk or who have developed hepatic disease.

Objectives: The overarching objective of this research is to progress drug development tools to provide a pathway for evaluating novel therapies for AATD.

The near-term objectives are as follows:

• Advance the activities of the AATD consortium to serve as a platform to aggregate data from available clinical trials, registries, and other studies to assess longitudinal dynamics of biomarkers, clinical measures, or other clinically meaningful metrics specific to AATD.
• Develop tools that can have the potential to optimize enrollment and inform clinical trial design.
• Develop preliminary versions of clinical trial endpoints, including clinical outcomes and potential surrogate endpoints, that can be incorporated into future drug development programs

5. Lysosomal Diseases (LD) Consortium

Description:

The Critical Path for Lysosomal Diseases (CPLD) Consortium is a consortium that was launched September 2023. It brings together multiple experts in lysosomal diseases (LDs) including academic researchers, medical product developers, patient communities and advocacy organizations, and regulators to generate actionable solutions to accelerate drug development for lysosomal diseases.

Goals/Objectives:

• Create a solutions-focused workstream for CPLD focusing on various cross-cutting solutions for unmet needs common across multiple LDs.
• Aggregate and integrate patient-level data for the development of tools, methods, and processes to characterize the disease pathology and natural history, identify drug targets, increase efficiency, predictability, and productivity of clinical development of therapies
• Convene public meetings focused on addressing various aspects of unmet needs and proposed solutions for lysosomal drug development

6. Critical Path for Rare Neurodegenerative Diseases (CP-RND)

Description:

The Critical Path for Rare Neurodegenerative Disease (CP-RND) public-private partnership (PPP) launched September 2022. It brings together multiple experts in rare neurodegenerative diseases, including ALS, as well as private entities, patient communities and advocacy organizations to accelerate and advance understanding of disease pathology, treatment options, diagnostics, and drug development

Objectives:

• Advance regulatory science and scientific research to support and accelerate the development of drugs for patients with ALS and other rare neurodegenerative diseases by providing an integrated environment for scientific discoveries to address tangible knowledge gaps that accelerates translation from bench to bedside
• Aggregate and integrate patient-level data for the development of tools, methods, and processes to characterize the disease pathology and natural history, identify drug targets, increase efficiency, predictability, and productivity of clinical development of therapies, including advancement of therapeutic development and establishment of clinical trial networks
• Accelerate the development of treatments for ALS by establishing partnerships, consortia, and collaboration with other public and private entities, patient-advocacy groups and individuals in ALS and other rare neurodegenerative diseases

The Grantee is expected to function independently but is encouraged to network with other organizations when possible or when it will improve the project outcomes.

To be successful, an applicant must satisfy the criteria set out in Section 566 of the Federal Food, Drug, and Cosmetic Act and content described in the Review Criteria within this NOFO.

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

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

Critical Path Institute

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 HHS 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 FDA 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 their 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.

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

This NOFO does not require cost sharing as defined in the HHS Grants Policy Statement.

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

The FDA 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 FDA 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).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. For this specific NOFO, the Research Strategy section is limited to 30 pages.

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

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

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

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

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

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

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

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

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

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:

• Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

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.

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

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

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

Foreign (non-U.S.) institutions must follow policies described in the HHs Grants Policy Statement, and procedures for foreign institutions.

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

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, the electronic system for grants administration. FDA 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 FDA Policy on Late Application Submission.

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

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

This initiative is not subject to intergovernmental review.

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

All FDA awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement and 45 CFR 75, 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.

Awards issued under this FOA will be incrementally funded awards for each budget period. NIH and FDA will not issue any awards under this FOA for a single budget period for multiple years.

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to FDA. See Section III of this NOFO for information on registration requirements.

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 assigned FDA Grants Management Specialist and responsiveness by components of participating organizations. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

Post-submission materials are those submitted after submission of the grant application but prior to objective review. They are not intended to correct oversights or errors discovered after submission of the application. FDA accepts limited information between the time of initial submission of the application and the time of objective review. Applicants must contact the assigned Grants Management Specialist to receive approval, prior to submitting any post submission materials. Acceptance and/or rejection of any post submission materials is at the sole discretion of the FDA. Any inquiries regarding post submission materials should be directed to the assigned Grants Management Specialist.

Only the review criteria described below will be considered in the review process.

The applicant must also provide assurance that it will not accept funding for a project from any organization that manufactures or distributes products regulated by the Food and Drug Administration unless it provides assurances in its agreement with the Food and Drug Administration that the results of the project will not be influenced by any source of funding.

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/technical merit of each applicant. The applications will be evaluated on needs and requirements identified in the full text section and the review criteria.

Does the applicant address the needs of the consortiums and other collaborations that it will coordinate to advance FDA's regulatory science needs that will lead to meaningful public health impact?

Is the scope of activities proposed appropriate to meet those needs?

Does the applicant bring unique advantages or capabilities to these projects?

Is there evidence that PD(s)/PI(s) Is there evidence that well suited for the project types identified?

Do proposed staff, (PD/PI, researchers, collaborators) have the bandwidth to fully fulfill their role in the types of projects identified?

Does the applicant have scientific and technical expertise (or ability to obtain) across multiple therapeutic areas/scientific/biomedical fields to lead the consortia/project?

Does the applicant have a demonstrated an ongoing record of relevant accomplishments?

Does the applicant have complementary and integrated expertise; is their leadership approach, governance, and organizational structure for the projects

Does the applicant provide innovative approaches to facilitating the collaborations and outcomes for each identified project?

Does the application provide viable plans for gaining additional funding from sources beyond FDA (e.g., non-FDA federal funds, non-federal funds, foundations, institution funds and other allowable funding?

Does the applicant employ a sound and effective approach/methodology to accomplish its goals and objectives?

Does the applicant have a plan to assess for and address weaknesses and risks identified for each project?

Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the projects?

Are potential problems, alternative strategies, and benchmarks for success presented?

Does the applicant have a plan for measuring outcome metrics and impacts to public health for the projects?

Does the applicant have the ability to identify and/or hire sufficient number of qualified personnel to conduct the necessary research and project-manage all related activities, including review of project milestones for degree of completion, preparation/reporting of project findings, periodic and final reports, all for approval by FDA, and for subsequent distribution in the public domain?

Will the administrative and 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?

Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Has the applicant established alliances/collaborative partnerships to facilitate achievement of objectives the projects?

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.

If applicable, included:

Has the applicant and/or PD(s)/PI(s) worked collaboratively with FDA? Were the projects conducted by the applicant well aligned with FDA interests; did they have an impact on FDA? Did they resolve any problems in a timely and appropriate manner?

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.

When the proposed project involves human subjects and/or 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.

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 Animals Section.

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Objective Review Committee convened by the FDA, using the stated review criteria.

As part of the scientific review, all applications:

• Will receive a written critique.

Appeals of scientific review will not be accepted for applications submitted in response to this NOFO.

Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. The following will be considered in making funding decisions:

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

Successful applicants will be notified of additional information that may be required for other actions leading to an award. The decision not to award a grant or to award a grant at a particular funding level, is discretionary and is not subject to appeal to any FDA or HHS official or board.

Information regarding the disposition of applications is available in the HHS 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 NOFO will be subject to terms and conditions found in the HHS Grants Policy Statement.

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

All FDA grant and cooperative agreement awards include the HHS Grants Policy Statement as part of the NoA.

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 condition of receiving the grant, to administer 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. 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 FDA grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• 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 reasonable accommodations and making services accessible to them, 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 FDA's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what FDA's expectations are for institutions and the individuals supported on FDA-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with 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), FDA 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 FDA grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and FDA 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 FDA programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, FDA's purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and FDA as defined below.

Awardee Responsibilities

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

1. Participate in site visits or attend meetings as requested by the FDA. A portion of the budget should be reserved for such travel.

2. Coordination with FDA, as they may request data be made available through speaking engagements and publications, presentations at scientific symposia and seminars, while making sure that confidentiality and privacy of the data is protected.

3. The awardees will provide FDA any data obtained from investigations if requested by FDA.

4. Any publication or oral presentation of regarding outcomes of this grant must undergo FDA Office of Research and Center review and approval process. This process can take 30-90 days.

5. Providing Board Briefings to the OTS Program

6. The awardee is responsible for preparing materials for meetings involving participants from FDA. Some meetings occur at FDA while others are conducted via teleconference.

7. Providing effective and efficient program and project management for each AIM

8. Ensure publications follow HHS Grant Policy in regard to approvals and acknowledgment of federal support

9. FDA will assist and approve (as deemed appropriate) the substance of publications, co- authorship of publications and data release.

FDA Responsibilities:

1. The FDA Program Office will be responsible for the normal scientific and programmatic stewardship of the award and an individual from this office will be named in the award notice.

2. An FDA Project Officer (PO) will have substantial programmatic involvement as described below. 3. The PO is the official responsible for the programmatic, scientific, and/or technical aspects of assigned applications and grants. The PO’s responsibilities include, but are not limited to, post- award monitoring of project/program performance, including review of progress reports and making site visits; and other activities complementary to those of the Grants Management Officer (GMO). The PO and the GMO work as a team in many of these activities.

6. FDA will assist and approve (as deemed appropriate) the substance of publications, co- authorship of publications and data release.

Areas of Joint Responsibility include:

1. Projects will require FDA Program Office approval prior to implementation/ initiation.

2. During performance of the award, the FDA Program Office, in consultation with FDA SMEs, may provide appropriate assistance, advice and guidance. The role of the FDA Program Office will be to facilitate and not to direct the activities. The FDA/ Program Office will facilitate liaison activity for partnerships, and provide assistance with access to FDA supported resources and services

3. At the start of and throughout each project, the FDA Lead and grantee will assess the need for additional agreements (i.e., Material Transfer Agreements, Data Transfer Agreements) and come to an understanding on how to best make project outcomes available for public benefit.

PROGRAM INCOME:

1. The grantee is required to report any Program Income generated during the Project Period of this grant. Except for royalty income generated from patents and inventions, the amount and disposition of Program Income must be identified on lines 10 (l), (m), (n), and (o) of the grantee's Federal Financial Report (FFR) SF-425.

2. Examples of Program Income include (but are not limited to): fees for services performed during the grant or sub-grant period, proceeds from sale of tangible personal or real property, usage or rental fees, patent or copyright royalties, and proceeds from the sale of products and technology developed under the grant.

3. Any Program Income generated during the Project Period of this grant by the grantee or sub-grantee is subject to the Addition Alternative for Program Income and, therefore, must only be used to further the goals of the project for which this grant was awarded.

PRIOR APPROVAL:

All requests that require prior approval must include the award number and bear the signature of an authorized official of the grantee business office as well as that of the PI/PD. Any requests involving funding issues must include a new proposed budget and a narrative justification of the requested changes. If a grantee questions whether prior approval is required for an activity or cost, they should contact the assigned Grants Management Specialist prior to expenditure of funds for clarification.

Below are activities that require prior approval from FDA:

• -Change in scope or objectives
• -Change in key personnel
• -Change in grantee organization
• -Deviation from terms and conditions of the award
• -Carryover of unobligated balances
• -No cost extensions
• -Significant rebudgeting

The awardee is responsible for timely publication and public release and dissemination of results, Data (under this cooperative agreement, Data is as defined in the HHS Grants Policy Statement to mean recorded information, regardless of the form or media on which it may be recorded, and includes writings, films, sound recordings, pictorial reproductions, drawings, designs or other graphic representations, procedural manuals, forms, diagrams, work flow charts, equipment descriptions, data files, data processing or computer programs (software), statistical records, and other research data) and other products of the study, concordant with an approved plan for making Data and materials available to the scientific community and FDA.

FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community. Please see the FDA Public Access Policy.

Awardees will retain custody of and have primary rights to the Data developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and FDA policies. Any publications, Data or other copyrightable works developed under this grant may be copyrighted without prior FDA approval. In all cases, whether FDA funded all or part of the project or program resulting in the Data or other copyrightable work, FDA must be given a royalty-free, nonexclusive, and irrevocable license for the Federal government to reproduce, publish, or otherwise use the material and to authorize others to do so for Federal purposes.

At the start of and throughout each project, the FDA and grantee will assess the need for additional agreements (i.e., Material Transfer Agreements, Data Transfer Agreements) and come to an understanding on how to best make project outcomes available for public benefit.

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 HHS 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 HHS Grants Policy Statement. FDA NOFOs outline intended research goals and objectives. Post award, FDA 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 FDA 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 HHS Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 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 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Additional Reporting Requirements:

All FDA grants require annual financial and performance progress as stated in Section III. This award has additional performance reporting requirements as outlined below.

Performance:

Annual Progress Reports for each year of the cooperative agreement along with monthly status reports are required. All these reports should contain the content needed by FDA and documented in an agreed upon format between FDA and the Grantee. FDA will review the progress of the Program and take into account the following as we complete overall reporting, RPPR checklists and data calls related to this grant:

1) overall management and accomplishments of the Program,

2) interactions with FDA,

3) achievement of project milestones and deliverables, and

4) impact of projects on FDA’s public health mission.

The following Reports are required to assess the Grant activities:

1. Monthly status reports

2. Annual Budget Planning Report

3. The Annual Progress Report (reported in the RPPR) reports on the entire past year of the cooperative agreement and includes all projects/Aims that were started, in progress and projects that were completed during the time period.

It will include:

• -Summary information on each project
• -Public Health Impact-defined as how outputs from the project/aim were utilized/applied and how they impacted product development and FDA’s Public Health Mission. If still in progress, it is acceptable to describe how it will impact public health
• -Accomplishments-defined as what activities were completed
• -Issues and concerns encountered
• -Solutions used to resolve issues

4. Cumulative Accomplishments and Impact Report: Includes a listing of the accomplishments from the current year, cumulative impact on product development and FDA’s Public Health Mission of current and previous years.

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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Patricia Koussis
(CDER)
Email: Patricia.Koussis@FDA.HHS.GOV

Terrin Brown
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Email: Terrin.Brown@fda.hhs.gov

Recently issued policy notices may affect your application submission. A full list of policy notices published in the Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS 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), Section 566 of the FD&C Act, and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.