Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

The National Institute of Allergy and Infectious Diseases (NIAID) supports extramural research focused on understanding, controlling and preventing diseases caused by virtually all infectious agents. In response to threats presented by emerging infectious diseases, the NIAID Division of Microbiology and Infectious Diseases (DMID) has established research programs to facilitate development of countermeasures for certain pathogens. The purpose of this Funding Opportunity Announcement (FOA) is to solicit research applications for projects focused on preclinical development of lead candidate therapeutics, vaccines, or clinical diagnostics that address select NIAID Emerging Infectious Diseases/Pathogens, as defined below.

For the purpose of this FOA, lead candidate is defined as a candidate product, or a collection of optimized products (e.g. lead candidate series), for which proof-of-concept data have been obtained and preclinical development is defined as all activities beyond lead candidate identification (therapeutics or vaccines) or assay/platform/prototype development (diagnostics). Examples of supported research areas include: lead optimization; efficacy testing, safety evaluation; stability testing; manufacturing; development of broad spectrum platforms and/or production technologies; optimization of products or technologies; process development; scale-up; production of quantities sufficient for preclinical regulatory requirements; IND-enabling activities required for initiation of Phase I clinical trials; and diagnostic validation. Priority will be given to projects that address the greatest public health concerns.

The National Institutes of Health (NIH) and other agencies in the Department of Health and Human Services (DHHS) support development of countermeasures to protect the public from infectious diseases. In 2002, the NIH initiated development of strategic plans to counter threats presented by emerging infectious diseases. As a component of these plans, NIAID was assigned responsibility for research leading to and development of candidate countermeasures (therapeutics, vaccines, diagnostics and platform technologies) against a growing list of emerging pathogens. NIAID established the Partnerships program to support discovery, preclinical research, product development and eventual commercialization of candidate products that address specific pathogens/agents. This FOA reflects current priorities outlined in the NIAID Strategic Plan for Biodefense Research, National Strategy for Combating Antibiotic-Resistant Bacteria (CARB), National Action Plan for Combating Multi-drug Resistant Tuberculosis, HHS Public Health Emergency Medical Countermeasures Enterprise Implementation Plan, the HHS 2010 Medical Countermeasure Review, and Homeland Security Presidential Directive 18: Medical Countermeasures against Weapons of Mass Destruction.

The objective of this FOA is to support milestone-driven preclinical research that will advance the development and/or production of lead therapeutics, vaccines or medical diagnostics for select Emerging Infectious Diseases/Pathogens described below. Each application must propose a research and development project whose goal is to advance an already identified lead candidate/platform. Proposed projects are not required to result in a "final" product, nor is it necessary to propose completion of the product development process up to the point of readiness for clinical trials or validation within the time frame of the project. Applications that would significantly advance a candidate product toward clinical or field usefulness are responsive and encouraged. Required industrial participation on applications from academic institutions (see below) will facilitate appropriate and validated product development activities. Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) are strongly encouraged to obtain expertise in the areas of product development planning and target product profile development in general, and regulatory matters in particular. Expertise needed to fulfill project objectives may be retained as defined effort or may be included as periodic consultation on specific issues.

Descriptions of supported countermeasure development activities and targeted pathogen categories are presented below:

Therapeutics

This FOA will support preclinical development of therapeutics against select NIAID Emerging Infectious Diseases/Pathogens (antimicrobial-resistant bacteria and emerging viral pathogens; see below), including immune-based and host-targeted forms, with emphasis on broad-spectrum therapeutics and those targeting pathogens for which no standard clinical treatment exists or for which drug resistance poses a significant public health concern. Therapeutics of interest include small molecules, biopharmaceuticals, nucleic acids, or peptides to be used as monotherapy or in combination, or as adjunctive therapy, with other drugs. Projects must initiate with a single candidate therapeutic or lead candidate series. For projects initiating with a lead series, down-selection to a single lead candidate must be accomplished within the first two years of the project period.

Immune-based therapeutic projects may focus on broad-spectrum or pathogen-specific immunotherapeutics. Of particular interest are immunotherapeutics that would enable prevention of infection or intoxication in the face of an immediate threat, protection of immunocompromised individuals, or post-exposure treatment to suppress infection and disease. NIAID encourages development of immunotherapeutics that directly affect pathogens and/or therapeutic approaches to stimulate non-specific immunity. Passive treatments may be especially valuable during the acute emergence of infectious diseases and may complement the use of antimicrobial drugs or vaccination programs to optimize protection.

Host-targeted therapeutic projects must focus on a host-encoded function required for infection, replication, spread and/or pathogenesis by one or more pathogens. Host-targeted therapeutic candidates that act primarily by stimulating the host immune response through direct regulation of interferon expression will be considered non-responsive. For host-targeted intervention projects, applicants must clearly define the specific required host-pathogen interaction(s) for development of the corresponding targeted therapeutic(s). NIAID encourages development of therapeutics that target specific host functions/pathways that are required for infection and pathogenesis by unrelated pathogens. Of particular importance for novel host-targeted therapeutics is consideration of proposed work that directly addresses the clinical and regulatory pathway to product registration and potential hurdles such as demonstration of pathogen susceptibility and therapeutic efficacy using non-standard in vitro assays and in vivo disease models, as well as potential toxicity issues.

Applications for development of a broad spectrum anti-infective against multiple targeted Emerging Infectious Diseases/Pathogens are encouraged. A broad-spectrum therapeutic is defined as a therapeutic agent that targets a common, invariable, or essential component of different strains or classes of microbes, or one that targets a host function required for infection and/or disease.

Therapeutics projects supported by this FOA must focus on previously-identified, well-characterized, candidate leads or lead candidate series and/or targets for the following select pathogen categories:

Antimicrobial-Resistant Bacteria

This initiative will support development of new or improved therapeutics for select bacterial pathogens for which drug resistance poses a significant public health concern. Responsive applications must target at least one bacterial pathogen listed in the Centers for Disease Control and Prevention’s Antibiotic Resistance Threats in the United States, 2013 report). Projects focused on drug-resistant Mycobacterium tuberculosis are limited to development and/or evaluation of therapeutic entities that are not currently licensed for another indication (repurposed drugs). Antibacterial categories supported by this FOA include, but are not limited to, narrow-spectrum drugs, broad-spectrum drugs, innovative therapeutic approaches/strategies, drugs targeting novel mechanisms, or adjunctive therapeutics.

Emerging Viral Pathogens

This initiative will support development of new or improved therapeutics for emerging viral pathogens of public health concern. Responsive applications must target at least one viral pathogen on the Emerging Infectious Diseases/Pathogens list. Antiviral categories supported by this FOA include, but are not limited to, broad-spectrum antivirals, immunotherapeutics, or host-targeted therapeutics. Of particular interest are projects focused on development of a candidate antiviral effective against Zika virus (ZIKV).

Therapeutics projects supported by this FOA may include, but are not limited to, one or more of the following preclinical activities:

• Lead optimization; medicinal chemistry; structure/activity relationships;
• Synthesizing, purifying, and testing lead candidates for efficacy and toxicity in model assays and preclinical in vivo systems;
• Performing preliminary pharmacokinetic (PK) and pharmacodynamics (PD) analyses on lead candidates;
• Preclinical testing for efficacy and safety in animals;
• Testing and validation of efficacy in in vitro or in vivo models (e.g., rodents, nonhuman primates);
• Optimization of dose, dosing interval, and route of delivery in preclinical evaluation or in animal models;
• Methods to modify existing drugs/therapeutics to improve economy of production, half-life in vivo, target affinity, neutralization potency, microbial clearance rates, or tissue accessibility; or to decrease adverse side effects of administration;
• Evaluation of the potential for the emergence of drug/therapeutic resistance in model systems;
• Assessing bioavailability and mechanism of action;
• Process development for the manufacturing of a therapeutic, including QA/QC, methods for product recovery, characterization, purification, identity, stability etc.;
• GLP or cGMP production to generate sufficient product to conduct pre-clinical and for future Phase I clinical studies; and
• Performing required benchmarks for successful submission and review of an IND application by the FDA.

Vaccines

This FOA will support preclinical development of candidate vaccines against NIAID Emerging Infectious Diseases/Pathogens, focusing on multivalent/universal forms, therapeutic forms, or vaccines targeting select pathogens (see below). Development of candidate vaccines should initiate with previously-identified, well-characterized immunogens. Projects are expected to include proof-of-concept in animal models, preclinical evaluation, and if warranted, scale-up production under GMP to provide sufficient quantities for pre-clinical FDA-required animal studies. Projects must focus on development of a candidate vaccine aligned with one of the following categories:

Multivalent/Universal Vaccines

Multivalent or universal vaccines are defined as broad-spectrum vaccines that provide protection against a group of taxonomically-related pathogens, or two or more unrelated pathogens. Vaccines characterized by broad-spectrum activity in this class include cross-protective forms, which induce an immune response against constant components of two or more microbes, and multiple component forms, which include elements that protect against microbes that are different, and may or may not be related. Examples of this vaccine category include, but are not limited to, a universal influenza vaccine or a multivalent vaccine that protects against multiple flaviviruses.

Therapeutic Vaccines

Therapeutic vaccines are defined as those vaccines that can be delivered post-diagnosis to simplify, reduce, and/or shorten, or eliminate complicated treatment regimens, or reduce development of antimicrobial resistance. Examples of therapeutic vaccines include, but are not limited to, forms used for combination treatment of infections caused by Mycobacterium tuberculosis or Burkholderia pseudomallei.

Vaccines with Small Market Potential

NIAID encourages development of monovalent or multivalent prophylactic vaccines characterized by small market potential, particularly vaccines that target pathogens for which no licensed vaccine exits. Examples include, but are not limited to, vaccines against Coccidioides spp., Lyme borreliosis, and Zika virus (ZIKV).

For all vaccine projects, approaches should consider the ultimate potential of a candidate vaccine to quickly induce safe and protective responses in a diverse civilian population. Vaccine projects may include, but are not limited to, one or more of the following product development activities:

• Lead vaccine candidate optimization;
• Evaluation of safety, toxicity and immunogenicity in animals;
• Evaluation of efficacy in challenge models where appropriate animal models are available;
• Optimization of dose and route of delivery in preclinical evaluation;
• Optimization of production methodology including process development;
• Scale up and production of candidate vaccines including cGMP production;
• Process development for the production of vaccine components, including Quality Assurance (QA)/Quality Control (QC), methods for product recovery, characterization, purification, identity, stability, etc.;
• Manufacturing under GLP or cGMP to provide quantities sufficient for preclinical and early clinical evaluation;
• Performing preclinical testing for safety, toxicity, and efficacy in animal models and other benchmarks required for successful submission and review of an Investigational New Drug (IND) application by the Food and Drug Administration (FDA);
• Optimization of delivery platforms, antigen and adjuvant combinations/formulations;
• Advanced development of non-needle vaccine delivery systems, such as transdermal, oral, or nasal delivery; and
• Advanced development of formulation methodologies that obviate the need for cold-storage of the resulting product and/or extend shelf-life.

Diagnostics

This FOA will support development of rapid, sensitive, specific, simple, and cost-effective diagnostics for primary healthcare settings (hospitals and point-of-care). Of particular interest are technologies that analyze clinical samples more accurately than current platforms and ideally have a target diagnostic test time of 1 hour or less to final result, including time required for clinical sample processing. The following categories are supported: diagnostics that facilitate antibacterial stewardship and diagnostics for Zika virus (details below). Projects must focus on previously identified pathogen- or host-specific targets or technologies amenable to large-scale production and validation for clinical diagnosis and point-of-care use. It is anticipated that the medical diagnostics developed through this initiative will aid healthcare providers in diagnosing individuals exposed to and/or infected with targeted NIAID Emerging Infectious Diseases/Pathogens and will be developed with the eventual and ultimate goal of obtaining FDA clearance. However, FDA clearance need not be the final result of the proposed research project period. Applications for projects that would significantly advance a candidate diagnostic product/platform toward clinical utility are responsive and encouraged. As detailed in the following sections, proposed diagnostics must be culture-independent and detect multiple targeted pathogens in human clinical samples.

Culture-Independent Diagnostics

The proposed diagnostic must directly detect targeted pathogens in a specified clinical sample type (swabs, sputum, blood, serum, cerebrospinal fluid, urine, stool, etc.) isolated from individuals at multiple stages of infection. Of particular interest are diagnostic technologies that detect the target pathogen(s) in at least one normally sterile specimen type (i.e. blood, cerebrospinal fluid, or pleural fluid), allowing for validation of the technology in a setting where colonizing organisms are not a complicating factor. For culture-independent diagnostics focused on sample types that may be affected by commensal/colonizing organisms, such as those analyzed for HAP/VAP, applicants must specify how contamination with colonizing organisms will be addressed.

Note: A short incubation step which enables the platform to provide all relevant information < 3 hours is acceptable.

Multiplex Platforms

Proposed multiplexed diagnostic platforms should enable differential detection of multiple agents in clinical specimens and rapidly distinguish whether an individual is infected with a biological threat agent or a common infection with similar, generalized symptoms. Of particular interest are flexible platforms capable of integrating new tests for agents as required, including detection of modified or new targets, and innovative platforms that provide diagnostic information on potential early, non-specific symptoms.

For this FOA, proposed diagnostics must also align to one of the following programmatic diagnostic priorities:

Diagnostics that Facilitate Antibacterial Stewardship

Proposed diagnostics must target at least three bacterial pathogens listed in the Centers for Disease Control and Prevention’s Antibiotic Resistance Threats in the United States, 2013 report. Priority will be given to diagnostic technologies that rapidly detect the targeted bacterial pathogens and simultaneously provide phenotypic information on corresponding drug-resistance and drug-susceptibility relevant to clinical decision making. Detection of host factors predictive of bacterial infection that may provide clinically actionable information may also be included.

Diagnostics for Zika Virus (ZIKV)

Projects may focus on development of improved, enhanced or novel diagnostic technologies and platforms for detection and identification of ZIKV and/or modification of a candidate diagnostic platform to target ZIKV. Of particular interest is the development of improved serologic assays that distinguish ZIKV from other flaviviruses (especially dengue virus (DENV) and yellow fever virus (YFV)) in point-of-care diagnoses and/or clinical laboratory applications.

For all diagnostics projects supported by this FOA, the following general diagnostic performance characteristics are of greatest importance:

• Proposed diagnostic test time of 1 hour or less for pathogen/toxin identification and/or 3 hours or less for antibiotic susceptibility.
• Sensitivity equivalent to or exceeding that for FDA-cleared diagnostics for targeted agent(s). If no FDA-cleared test is available for the targeted agent(s), sensitivity must be equivalent to or exceed that for FDA-cleared tests for similar agent(s).
• Specificity should be equivalent to or exceed that for FDA-cleared diagnostics for targeted agent(s) from the same sample type.

In addition, the following characteristics are desirable, but not essential to prototype diagnostics developed under this FOA:

• Easy to use (i.e. integrated, closed sample-to-answer system with automated data analyses and/or result presentation and with minimal operator training and expertise required).
• Random access (i.e. proposed instrument should allow samples to be run as needed).
• Adaptable (i.e. platform capable of integrating new diagnostic tests for new /modified agents as required).
• Non-nucleic acid amplification-based. Due to limitations of previous Nucleic Acid Amplification Tests (NAATs) in detecting bacteria from normally sterile sites, non-NAAT approaches are of higher priority unless a strong rationale is presented that documents why the proposed technology will overcome the challenges of predecessor NAATs.
• Cost-effective (i.e. projected production and operating costs should be consistent with current clinical platforms.

Examples of potential diagnostics development activities to be supported include, but are not limited to:

• Integrated sample-to-answer technologies with all components and subsystems (clinical sample processing, analyte detection, test result determination and reporting, etc.) completely automated and integrated into an operational platform that does not require any manual manipulation steps after the clinical sample has been loaded into the platform;
• Integrated sample-to-answer technologies, including sequencing-based approaches, capable of high throughput multiplex screening using analytes or signature biomarkers to identify human immune or other physiological response to infection;
• Technologies and capacity for high throughput, automated data management, output and analyses;
• Use of nanotechnology, microfluidic-based systems or other novel or innovative system to process large numbers of patient samples, and;
• In vivo imaging methods and development of contrast reagents for visualization of pathogens or host immune responses in vivo.

Applications including the following will be considered non-responsive and will not be reviewed:

• Projects lacking appropriate proof-of-concept data supporting the candidate therapeutic, vaccine or diagnostic platform.
• Projects from academic institutes that lack substantive investment by at least one industry participant.
• Projects focused on development of a therapeutic that acts primarily by stimulating the host immune response to infection through direct regulation of interferon expression.
• Projects focused on repurposing a licensed drug as a therapeutic for Mycobacterium spp.
• Clinical trials (all phases).
• Projects on AIDS or HIV.

All projects submitted to this FOA must demonstrate substantive investment by at least one industry participant. For the purpose of this FOA, "industry" is defined as a large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, or chemical company, or a related non-profit entity with an established track record in product development. Substantive investment" is defined as a significant commitment of one or more resources to the project including, but not limited to: product development support/guidance, personnel, in kind contributions of materials and/or reagents (i.e. chemical libraries, innovative biotechnology platforms, scale up of CGMP chemical synthesis or production, etc.), provision of animal or other laboratory models for evaluation, subcontracts, data management resources, regulatory support, or alterations/renovations of facilities or provision of equipment to address biohazard concerns. The PD(s)/PI(s) of the project may be affiliated with either industry or an academic organization; however, if the PD(s)/PI(s) is from academia, an industrial partner must be identified in the application. PD(s)/PI(s) are strongly encouraged to obtain expertise in the areas of product development planning and target product profile development in general, and regulatory matters in particular. There is no requirement for an academic participant on applications submitted by industrial organizations.

NOTE: Refer to Section IV. Application and Submission Information for specific requirements for the PHS 398 Research Plan, and Other Project Information (for example, a Product Development Strategy Attachment).

NOTE: PD(s)/PI(s) are strongly encouraged to obtain expertise in regulatory matters associated with product development. Expertise may be retained as defined effort or may be included as periodic consultation on specific issues.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

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. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Kelly Poe, Ph.D.
Telephone: 240-669-5036
Fax: 301-480-2408
Email: Kelly.poe@nih.gov

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

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

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

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

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

Other Attachments: Applicants are required to include a Product Development Strategy that includes both a Milestones and Timeline and a Product Development Plan section. The Product Development Strategy attachment must be in pdf format with a filename of Product_Development_Strategy.pdf. Applications lacking a required section of the Product Development Strategy section will be deemed incomplete and will not be reviewed.

The overall Product Development Strategy, made up of the "Milestone and Timeline" and the "Product Development Plan sections," is limited to 12 pages. (Note: Applicants must not add additional attachments to circumvent page limits.)

Milestones and Timeline: Applicants are required to provide detailed project performance and timeline objectives in a section entitled Milestones and Timeline. This section must be no more than 5 pages and must include:

• A clear description of all interim objectives (research and/or developmental milestones) to be achieved during the course of the project. Applicants also must identify any impediments that could require a revision in the work plan or milestones with a discussion of alternative approaches.
• Detailed quantitative criteria by which milestone achievement will be assessed.
• A detailed schedule or timeline for the anticipated attainment of each milestone and the overall goal(s).

Product Development Plan: Applicants are required to provide detailed development plans in a section entitled Product Development Plan . This section must be no more than 7 pages and must include:

• A statement of the intended use/indication of the proposed product and public health gap the product is intended to fill.
• A statement of the value of the project, including lay description of key technology objectives, innovation, and advantages compared to competing products, technologies, or services.
• A clear description of the goal(s) of the project, including one (or more) intermediate products (tools), final product(s) or stage(s) of product development to be completed during the award period. A specific final product profile that is intended for licensing indication is not requested.

Additionally, the Product Development Plan must include descriptions pertaining to preclinical product development activities pertaining to the product proposed. For the purpose of this FOA, preclinical is defined as all activities beyond lead candidate identification or diagnostic assay/platform/prototype development or vaccine technology proof-of-principle. Please see below for a list of points to be discussed as part of the Product Development Plan based on the type of product proposed.

Product Development Plans for vaccine or therapeutic projects should summarize:

• The performance specifications and features the product should have in order to provide immunological and/or therapeutic benefit.
• A description of the candidate product or lead series as it is currently configured.
• A description and developmental status of the assays for product release and characterization, including activity and efficacy.
• Data that support the characterization and selection of the candidate product for further development. Specifically for vaccines, a summary of data that demonstrates efficacy in in vitro assays and/or in vivo models for one or more of the selected agent(s). This includes: a detailed description of the assays and animal models, the choice of pathogen challenge, strain and route, and a rationale for the choice of animal model, pathogen challenge, strain and route, as well as for the outcome/endpoints selected; documentation that the animal infection experiments were performed under well-controlled experimental conditions.
• Discussions with FDA, if any, which are relevant to development activities for the candidate product/technology.

Product Development Plans for diagnostics projects should summarize:

• The performance specifications the product (diagnostic assay, method, technology, etc.) should have to demonstrate it is equivalent or superior to the gold standard for identifying the proposed agent(s), including clinical sensitivity in appropriate human samples, clinical specificity in appropriate human samples, analytical sensitivity (limit of detection), analytical reactivity (pathogen strains detected for each pathogen), analytical specificity (cross-reactivity), and analytical reproducibility (test replicates at different agent concentrations, at different sites, etc.). If no FDA-cleared test is available for the agent(s), the specifications should be equivalent to or exceed performance specifications of FDA-cleared tests for similar types of agent(s).
• Data that support the selection of the candidate product for further development, including an assessment of the present capacity of the diagnostic method, technology or assay to meet the performance specifications.
• Discussions with FDA, if any, which are relevant to development activities for the candidate product.

When appropriate, and as part of the Product Development Plan, applicants should document compliance with guidelines that govern GLP, as defined by 21 CRF (58), and CGMP, as defined by 21 CRF (211), manufacturing and/or IND/IDE enabling studies that will be performed under the project award as they would be applicable to eventual product licensure in the U.S. Applications for projects involving CGMP manufacture should ensure inclusion of appropriate personnel to provide regulatory guidance before, during and after manufacture.

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:

Research Strategy: Therapeutics and vaccine applications must address the following:

• Describe how the project will significantly advance the development of a candidate countermeasure against one or more of the specified pathogens.
• Provide and describe pre-established proof-of-concept data in support of the single candidate therapeutic/vaccine or lead candidate series to be developed, and plans to progress the candidate through preclinical development.
• For projects initiating with a lead series, clearly detail the process and timeline for down-selection to a single lead candidate within the first two years of the project period.
• For targeted pathogens that lack standard in vitro assays and/or in vivo disease models, describe the most appropriate experiments to demonstrate efficacy and address potential toxicity issues.

Diagnostics applications must propose development of a previously identified candidate diagnostic technology and include corresponding proof-of-concept data demonstrating feasibility. Applications for diagnostics in the final design stage(s) of product development in preparation for manufacture and validation are especially encouraged. All applications for research projects focused on diagnostics should include in the Research Strategy:

• A clear description of the capabilities of the method, technology or assay;
• A clear description of how the diagnostic/technology will be used; and
• Plans for determining the sensitivity, specificity and validation of the technology, assay or diagnostic.

Industry Participation: For applications from academic institutions, identify the industrial partner(s) and describe the organization's participation and investment in the project. All applications submitted by academic institutions must demonstrate substantive investment and participation in the project by at least one industry participant. There is no reciprocal requirement for applicants from industrial organizations to include an academic partner.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

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

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

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

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is this project likely to significantly advance the development of a therapeutic, vaccine or diagnostic against one or more of the select pathogens identified in this initiative? If the aims of the application are achieved, are important biomedical countermeasures or products likely to result?

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

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? For applications from academic institutions, does the research plan leverage appropriate industry involvement to accelerate therapeutic, vaccine or diagnostics product development, some aspects of which may not be inherently innovative?

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

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

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?

Product Development Strategy

Is the Product Development Strategy well-conceived and appropriate for the proposed countermeasure category? Are the Milestones and Timelines proposed to achieve the goals of the project appropriate and feasible? Is the proposed Product Development Plan feasible and appropriate for proposed and future product development?

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

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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

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

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

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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

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

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Michael R. Schaefer, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3364
Email: mschaefer@niaid.nih.gov

Kelly Poe, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5036
Email: Kelly.poe@nih.gov

Cynthia Rodriguez, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5391
Email: cynthia.rodriguez@nih.gov

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.