Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH 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 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Overview

The Chemical Countermeasures Research Program (CCRP) supports the discovery and early preclinical development of medical countermeasures (MCMs) to treat and/or prevent serious morbidities and mortality resulting from high consequence public health chemical emergencies. A high consequence public health chemical event is when a large number of civilians are either deliberately or accidentally exposed to highly toxic chemicals. In this case, the MCMs should be easily accessible to first responders and local public health authorities for use in a mass casualty pre-hospital setting or as follow-on in-hospital treatments. The civilian chemical threat spectrum includes chemical warfare agents, toxic industrial chemicals, pesticides, ultra-potent synthetic (UPS) opioids, and others that have been identified by the Department of Homeland Security (DHS) as Chemicals of Concern (CoC). These compounds are highly toxic and MCMs are urgently needed to advance national medical and public health preparedness for, response to, and recovery from, chemical emergencies. MCMs should be safe and effective for adults, children, and the elderly.

The CCRP is a trans-NIH initiative established by the NIAID in 2006 and involves partnerships with the NEI, NIAMS, NICHD, NIEHS, NIDA, and NINDS to execute the overall NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Chemical Threats. Within the CCRP, the NIH Countermeasures Against Chemical Threats (CounterACT) program led by the NINDS in collaboration with the other CCRP Institutes supports research focused on civilian chemical MCMs. The CCRP has developed a comprehensive preclinical chemical MCM discovery and early development infrastructure that includes individual research project grants (RPGs) and cooperative agreements, SBIR project grants, contracts, MCM efficacy screening programs, and Interagency Agreements with agencies within the Department of Health and Human Services (HHS) and Department of Defense (DoD).

Support for basic research exploring mechanistic effects of toxic chemical exposure is provided through a suite of RPG NOFOs offered by various CCRP-participating institutes (NIAMS: PAS-21-245, NIEHS/NEI: RFA-ES-21-006, NINDS: PAR-23-027, NIDA: RFA-DA-23-056). Translational exploratory and developmental research is supported by an R21 mechanism (this NOFO). Translational research that focuses on discovery and early development of MCMs is supported by a cooperative agreement NOFO (PAR-22-209).

This R21 NOFO only accepts applications proposing exploratory translational research directly related to the preclinical development of novel treatment strategies/approaches that address adverse health effects after exposure to chemical threats. Applications for fundamental studies, such as proposals seeking to characterize pathways or molecular mechanisms of toxicity are not responsive to this NOFO and should instead be directed to the suite of basic research NOFOs previously detailed.

Chemicals of Concern (CoC)

This NOFO will only support projects developing MCMs against chemicals that have been identified by the DHS as high consequence public health CoC. CoC are organized within toxidromes established by the USG. Toxidromes group chemicals based on their primary modes of toxicity. One benefit of this approach is that a single MCM may be therapeutically effective against multiple different chemical threats within the same toxidrome.

The CoC toxidromes and examples include:

• Anticoagulants (e. g., brodifacoum, bromadiolone)
• Blood agents (e.g., hydrogen cyanide, hydrogen sulfide)
• Cholinergic Warfare and Pesticides (e. g., sarin, soman, parathion, phorate, aldicarb)
• Convulsant (e.g., picrotoxin, TETS, strychnine)
• Hemolytic/Metabolic (e.g., arsenic trioxide, thallium sulfate, arsine)
• Pulmonary (e.g., chlorine, phosgene, sulfur mustard, ammonia, sulfur dioxide)
• Ultra-potent Synthetic Opioids (e.g., fentanyl, carfentanil, acetylfentanyl, sufentanil, remifentanil)
• Vesicants (e.g., sulfur mustard and nitrogen mustard, Lewisite, phosgene oxime)

Note: The above examples of CoC are illustrative only as there are currently almost 200 chemicals in total. Applicants are strongly encouraged to contact the Scientific/Research contacts provided in this NOFO to confirm whether the proposed chemical threat(s) is of interest to the program.

Scientific Scope/Research Topics

This NOFO will only support translational research that is clearly relevant to the discovery of new or improved MCMs that will enhance national health preparedness and medical response capabilities during and/or after a public health chemical emergency. Projects supported by this NOFO are expected to generate preliminary preclinical, screening, and/or efficacy data that would facilitate the development of competitive applications for more extensive support from the NIH CounterACT Cooperative Agreement program and/or related initiatives.

The specific injuries caused by exposure to chemicals are often similar or identical to conditions observed in conventional clinical practice, e.g., respiratory depression, neovascularization, fibrosis, acute lung injury, seizure, runaway inflammation, and coagulopathy. As such, applicants are encouraged to repurpose products already approved by the Food and Drug Administration (FDA) for other indications as potential MCMs. Due to the urgency in need, lengthy time, and expense in bringing a new compound to regulatory approval, such drug repurposing strategy may expedite the development and regulatory pathway for the new MCM indication.

Lastly, the ultimate intended use of the MCM must be considered (i.e., concept of use), e.g., timing and route of administration consistent with its effective use during a civilian mass casualty emergency setting. Compounds that are only effective when administered intravenously (IV) in the pre-hospital setting are not responsive since their use would be impractical at the scene of a mass casualty event. By contrast, IV-administrated therapeutics to prevent long-term or delayed effects after an acute exposure may be appropriate in the in-hospital setting where the use of IV products and supportive care is more plausible. Applications that propose research on prophylactic/pre-treatment use may be considered only if it is part of a project where post-exposure treatment is the major thrust. Conversely, applications that propose research wholly centered on prophylactics/pretreatments or post-exposure therapies that have no practical utility during a mass casualty scenario will be considered non-responsive to this NOFO and will not be reviewed. Similarly, applications proposing to develop environmental decontamination and/or analytical detection technologies and strategies will also be considered non-responsive and will not be reviewed.

Research Topic Examples

The categories of research supported under this R21 program includes, but is not limited to:

• Creation/validation of clinically relevant in vivo or in vitro (including 3D/organoid) models of the post-exposure lethality and serious near- and long-term chronic morbidities for the purpose of investigating treatment and prevention strategies
• Preclinical development of new molecular targeting agents, biologics, or novel strategies based on specific changes in signaling pathways and proteins/genes expression during the post-exposure injury process
• Evaluation of new combination treatment strategies and development of new agents to enhance the effectiveness of standard-of-care therapies
• Performance of high-throughput screens for discovery of chemical probes and molecular targeting agents
• Studies that use Artificial Intelligence/Machine Learning models for the purpose of investigating/discovering novel MCM strategies to modulate chemical toxicity
• Discovery of candidate therapeutics using primary and secondary screening to generate preliminary proof-of-principle in vitro and/or in vivo efficacy data
• Alternate routes of administration and/or dosing regimen for new or already FDA-approved therapies that would be safer, more effective, or easier to administer during a mass casualty scenario or for specific subpopulations (e.g., pediatric and pregnant) that are at higher vulnerability to the adverse effects of chemical intoxication
• Proposals seeking to repurpose/expand indications of already approved/authorized products. This may include, but is not limited to:
  • Alternate routes of administration and/or dosing regimen that would be safer, more effective, or easier to administer during a mass casualty scenario
  • Extending a previously observed protective effect of a promising novel and/or already FDA-approved compound(s) for one chemical threat to others, i.e., broadening the spectrum of activity

Applications Not Responsive to this NOFO

• Applications that do not propose research on chemical threats that are on the current DHS CoC List (check with Program staff prior to submission)
• Applications that propose therapeutics unlikely to be amenable during or after a mass casualty scenario. This includes therapeutics that must be administered prophylactically or within the first 15-30 minutes of exposure. For ultra-potent synthetic opioids only, the administration of therapeutic(s) may be as short as 5 minutes post-exposure. Applicants are encouraged to contact the Scientific/Research Contact(s) for additional guidance regarding timing.
• Applications addressing health outcomes after chronic chemical exposure, i.e., this NOFO only supports research on health effects after a single acute exposure event
• Applications proposing to develop environmental decontamination and/or analytical detection technologies and strategies
• Applications that only include basic research on mechanisms of toxicity from acute exposures of chemical threats

Non-responsive applications will not be reviewed.

Special Biosafety Certification

Many of the chemical threat agents of interest are extremely hazardous to humans. All applications must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment (See letters of support in Section IV). Special biosafety certifications may be required to conduct research with some chemical threat agents, e.g., chemical warfare agents. Therefore, applicants are encouraged to collaborate with laboratories and contract research facilities that are already certified to work with restricted chemical agents, when applicable. Applicants are strongly encouraged to contact the Scientific/Research Contacts listed in this NOFO for further information on working with restricted chemical agents.

Intellectual Property (IP)

For projects with pre-identified candidate MCM(s), the NIH encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy during the project period as appropriate, to ensure freedom to operate. Recipients of awards are encouraged to work closely with their institutional Technology Transfer (or Industry Relations) Office to identify and foster relationships with potential licensing and commercialization partners early in the preclinical development process. In accordance with the NIH Grants Policy Statement, PDs/PIs are expected to ensure that appropriate royalty agreements, patent filings, and all other necessary IP arrangements are managed in a timely manner and that commercialization plans are developed and updated over the course of the project, consistent with achieving the goals of the program. It is recognized that in the case of MCM, commercialization may be challenging. Therefore, applicants are encouraged to discuss alternative strategies with NIH Scientific/Research staff to get further guidance.

Annual Countermeasures Against Chemical Threats (CounterACT) Network Research Symposium

Awardees funded under this NOFO must participate in the annual network research symposium of CCRP-funded projects. Participation includes presentation of research progress achieved under the CCRP award.

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 NOFO.

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 Government

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are 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 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. 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.

See Notice of NIH’s Interest in Diversity, NOT-OD-20-031, see also, 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.

2. Cost Sharing

This NOFO 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, 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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in 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.

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 electronically 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:

Shardell Spriggs, Ph.D.
Telephone: 301-443-8189
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this 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 applicants must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment. The application must include a description of adequate protection and safeguards if required. Special biosafety certifications may be required to conduct research with some restricted chemical threat agents, e. g. chemical warfare agents. Applicants must include a letter from appropriate Department of Defense (DoD) officials if utilizing such restricted agents. (See letters of support)

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

Other Attachments: If applicable, applications are encouraged to include an Intellectual Property (IP) strategy section that is no more than 1 page. It is advisable that this be prepared in consultation with their institution's technology transfer officials.

This section should describe the IP landscape surrounding their proposed therapeutic candidate(s). Applicants should describe any known constraints that could impede their therapeutic discovery and development (e. g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed. If the applicant proposes using a therapeutic candidate(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any obstacles to achieving the goals of the program and development and commercialization of the therapeutic candidate.

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable.

Applicants should discuss future IP filing plans, but any such action must be performed in accordance with the NIH Grants Policy Statement (NIHGPS). For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e. g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved.

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

R&R or Modular Budget

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

The proposed budget should include travel support for the PD/PI to attend the Annual CounterACT Network Research Symposium for each of the proposed project years, in addition to other anticipated travel associated with the research. Post-doc, junior, and diverse investigators are encouraged to attend these meetings and budgets should be planned accordingly.

R&R Subaward Budget

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

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

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

Research Strategy

The applicant must address the following within the Research Strategy

Significance: This section describes how fulfilling the aims and objectives will generate substantial preliminary data and/or tools essential for more advanced MCM discovery and development efforts in future follow-on applications.

Investigator: This section describes the expertise within the team in therapeutic discovery, early-stage development and toxicology.

Innovation: Due to the nature of translational research supported by this NOFO, some studies and methodologies may not be considered innovative even though they are essential components of the overall project. Examples of this type of research include routine preclinical safety/toxicity evaluations and the use of previously established models of chemical-induced injuries to identify potential differences between specific subpopulations (e.g., adults versus pediatrics). This NOFO also supports and encourages repurposing products approved for other indications as long as the therapeutic approach using that product is for a new indication.

Approach: The concept of use of the proposed therapeutic must be explained in the application as it is applicable in a mass casualty/emergency setting. All proposed projects must have a strong biological rationale for the intended approach. Therefore, applicants to the program are urged to consider the rationale for the chosen model(s) and endpoints, and route and timing of therapeutic dosing. In those applications with an already identified candidate therapeutic compound, a description of the proposed product and how it will be ultimately used in humans, i.e., how and when it will be administered in the context of a civilian-based chemical emergency event should be clearly described.

The applicant should present a reasonable timeline for the work proposed.

Investigators should follow the NIH guidance for rigor and transparency in grant applications (see guidelines). This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These criteria should also be addressed when describing supporting data (if presented) and in the design of the proposed studies within the Research Strategy section (as appropriate).

Environment: The application must include a description of adequate protection and safeguards when working with highly toxic chemicals.

Letters of Support:

• Many of the chemical threat agents of interest to this announcement are extremely hazardous to humans. Applicants must include a letter from the appropriate institutional biosafety committee or institutional review entity indicating that studies are deemed safe for research personnel and the environment.
• A formal letter of support (and estimated budget, if applicable) must also be provided for all proposed collaborative, consultative, and contract arrangements.
• If applying from an academic institution, include a letter of support from the technology transfer official who will be managing existing and future intellectual property associated with this project.
• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions as appropriate and consistent with achieving the goals of the program.
• If collaborating with a private entity (e.g., regulatory support), include a letter of collaboration that addresses any agreement to provide service(s), any limits on the services that can be performed, any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place, if applicable. This letter should come from an official within the private entity who has the appropriate authority.

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.

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. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-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.

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

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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 NIH. 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 Center for Scientific Review and responsiveness by the participating ICs at NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

It is recognized that due to the nature of translational research, some studies may include existing methodologies such as standard tests and/or previously established models of chemical-induced injuries to explore a new scientific area. While these may not be considered especially innovative, they may nonetheless still be essential to advance the development of MCMs (and scientific knowledge).

Examples include but are not limited to preclinical safety evaluations, such as those striving to identify potential differences in vulnerabilities of specific subpopulation groups, or those seeking to determine the preclinical efficacy to repurpose FDA-approved products as MCMs.

Overall Impact

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).

Scored Review Criteria

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

Significance

Does the project 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 for this NOFO:

What is the likelihood that completion of the exploratory/developmental objectives will generate the tools and/or proof-of-principle efficacy data necessary to facilitate the development of competitive research applications for further MCM development?

How substantially will results from the proposed study contribute to the scientific foundation needed for future reduction of mortality and morbidity during and after emergency events involving the release of chemical threat agents?

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 for this NOFO:

How significant is the research team’s expertise in therapeutic discovery and early-stage development?

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 NOFO:

If the drug candidate has received prior FDA approval and is being repurposed for a different indication, how innovative is the therapeutic approach for the newly proposed indication?

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?

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?

Specific to this NOFO:

How sound is the scientific rationale for the selected model(s), chemical injuries, research tool(s), and potential therapeutic approach(es)?

How reasonable is the timeline for the work proposed?

How appropriate is the proposed post-exposure animal model, including timing and route of administration, for development of a therapeutic for civilian mass casualty/emergency settings?

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 NOFO:

How appropriate are the special biosafety precautions for working with highly toxic chemicals?

How complete is the safety assessment by the institutional biosafety committee or institutional review entity for the proposed studies, including the safety for research personnel and the environment?

How appropriate are the institutional approvals for working with restricted chemical agents?

How complete are the formal letters of collaboration for all proposed collaborative arrangements (and estimated budget) provided with the application, especially those utilizing restricted chemical agents?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

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

Renewals

Revisions

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.

Intellectual Property (IP) Strategy

If applicable, reviewers will comment on the following:

• Are potential issues regarding the IP landscape for the therapeutic being developed and the freedom to operate addressed?
• Do the IP Strategy attachment and related letters of support address potential concerns?
• Are there any known constraints that could impede the development of the therapeutic?
• Are IP filing plans described?
• If multiple institutions are involved, is IP sharing addressed?

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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 the Center for Scientific Review, 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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions :

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

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.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO 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: Recipient 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.

2. Administrative and National Policy Requirements

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

• Federal wide 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 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 NIH 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.htmlandhttps://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 https://www.hhs.gov/civil-rights/for-individuals/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.

Not Applicable

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.

4. Reporting

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 NOFOs 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

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

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]

For questions related to the overall CounterACT Program and/or neurological injury research:
Shardell Spriggs, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-443-8189
Email: [email protected]

For questions related to ocular injury research:
Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-435-8166
Email: [email protected]

For questions related to the CCRP and overall NIH initiative in chemical MCM research:
Dave Yeung, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-796-7237
Email: [email protected]

For questions related to dermal/vesicant-induced injuries:
Alexey Belkin, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-827-6475
Email: [email protected]

For questions related to pharmaceutical based agents:
Kiran Vemuri,Ph.D
National Institute on Drug Abuse (NIDA)
Phone: 301-435-4446
E-mail:[email protected]

For questions related to pulmonary injury research:
Srikanth S. Nadadur, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3296
Email: [email protected]

Jonathan Ivins, Ph.D.
Center for Scientific Review (CSR)
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: [email protected]

Jason Lundgren
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 669-2973
Email: [email protected]

Sheila Simmons
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-594-9812
E-mail: [email protected]

Pamela G Fleming
National Institute on Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: [email protected]

Jenny L Greer
National Institute of Environmental Health Sciences (NIEHS)
Phone: 984.287.3332
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.