Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Partnerships for Biodefense (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-013
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), invites research applications for projects that support preclinical development of lead candidate therapeutics, vaccines and related technologies, or diagnostics against NIAID Category A, B, or C priority agents. Applications must include a Product Development Strategy attachment and demonstrate substantive investment by at least one industrial participant.

Posted Date	February 26, 2013
Open Date (Earliest Submission Date)	May 2, 2013
Letter of Intent Due Date(s)	June 2, 2013
Application Due Date(s)	July 2, 2013, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	November, 2013
Advisory Council Review	January, 2014
Earliest Start Date	May, 2014
Expiration Date	July 3, 2013
Due Dates for E.O. 12372	Not Applicable

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

Purpose

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), supports extramural research focused on understanding, controlling and preventing diseases caused by virtually all infectious agents. In response to threats presented by bioterrorism and emerging infectious diseases, the NIAID Division of Microbiology and Infectious Diseases (DMID) has established research programs to facilitate development of countermeasures for certain pathogens and toxins.

With this FOA, the NIAID invites research applications for projects focused on preclinical development of lead candidate therapeutics, vaccines, or medical diagnostics that address NIAID Category A, B, or C priority pathogens and toxins (agents) (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Pages/CatA.aspx). This FOA also invites research applications for projects focused on preclinical development of candidate technologies (including adjuvants) that would improve vaccine effectiveness and/or simplify vaccine delivery to patient populations during a natural outbreak of an infectious disease or following the intentional release of an infectious agent. For the purpose of this FOA, lead candidate is defined as a candidate product or technology 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 or vaccine technologies). Examples of supported research areas may include: lead optimization; efficacy testing, safety evaluation; stability testing; manufacturing; adaptation of products or platform technologies to biodefense applications; 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; and diagnostic validation. Priority will be given to projects that address the greatest clinical need.

Industrial Participation

All applications submitted to this FOA by academic organizations must demonstrate substantive investment and participation in the project by at least one industry participant. For the purpose of this FOA, "industry" is defined as large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, and chemical companies (or non-profit agencies) with demonstrated experience in candidate product development. Substantive investment" is defined as a commitment of one or more resources 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 Good Manufacturing Process (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. Support for industrial partner activities may be included in the project budget. The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of the project may be affiliated with either an academic organization or industry. Applications submitted by industrial institutions do not require an additional industrial partner.

The NIH and other agencies in the Department of Health and Human Services (DHHS) support development of countermeasures to protect the public from bioterrorist threats and emerging infectious diseases. The biological agents deemed to pose the greatest threat are prioritized in the NIAID Category A, B and C priority agents list. In 2002, NIAID published the initial Strategic Plan for Biodefense Research (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/strategic_plan.pdf) and related research agendas (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/about/strategicplan.htm), outlining agency research and development objectives to address threats posed by Category A, B and C Priority Pathogens.

In 2007, NIAID published an updated Strategic Plan for Biodefense Research (http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/biosp2007.pdf). The updated Strategic Plan is consistent with the DHHS Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) Implementation Plan (http://www.hhs.gov/aspr/barda/phemce/enterprise/strategy/index.html), which outlined strategies for identifying medical countermeasure requirements and establishing priorities for their research, development and acquisition. The updated NIAID Strategic Plan continues to focus on translation of basic research to countermeasures, but with an emphasis shift from the one bug-one drug approach towards a more flexible, broad-spectrum approach. This approach is centered on development of countermeasures that are effective against multiple pathogens or toxins, development of technologies that can be widely applied to improve classes of products, and developing platforms that can reduce the time and cost of creating new products. The broad-spectrum approach recognizes the expanding range of biological threats and the limited resources available to address each individual threat.

The objective of this FOA is to support preclinical research that will advance the development and/or production of lead therapeutics, vaccines or associated technologies, or medical diagnostics specific for NIAID Category A, B, or C priority agents. Each application must propose a research and development project whose goal is to advance an already identified lead candidate/technology. Research projects are not required to result in a "final" product. Moreover, it is not necessary to propose to complete 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. Descriptions of priority countermeasure needs and examples of possible research projects are presented below.

NOTE: While clinical development strategies may be included within an overall project, this FOA will NOT support clinical trials. Utilization of human-derived material in pre-clinical studies in support of compliance with regulatory requirements is permitted and encouraged.

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.

Development of safe and effective therapeutics against NIAID Category A, B, or C agents is a high priority. This FOA will support preclinical development of therapeutics, including immune-based and host-targeted therapeutics, with special interest in broad-spectrum therapeutics and those targeting antimicrobial-resistant pathogens and/or pathogens for which no standard clinical treatment exists.

Immune-based therapeutics may include both broad-spectrum (innate immunity, for example) and pathogen- or toxin-specific immunotherapeutics (antibodies, for example). 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/toxins 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.

This program will also support development of therapeutics that target host-encoded functions required for infection, replication, spread and/or pathogenesis by one or more listed NIAID Category A, B, or C pathogens and potentially, additional non-listed pathogens. The development of therapeutics that target host-encoded functions provides a potential solution to emergence of microbial resistance and high developmental costs associated with treatments effective against only one microbe. Of particular interest are therapeutics that target specific host functions/pathways that are required for infection and pathogenesis by unrelated pathogens. For host-targeted intervention projects, applicants must clearly define the specific required host-pathogen interaction(s) for development of the corresponding targeted therapeutic(s).

The NIAID Strategic Plan for Biodefense Research emphasizes development of broad-spectrum therapeutics. An anti-infective characterized by broad-spectrum activity might target a common, invariable, or essential component of different classes of microbes and potentially be effective against traditional and non-traditional pathogens. Applications for development of either a broad spectrum anti-infective against multiple Category A, B, or C pathogens, or a broad-spectrum anti-infective against a non-listed pathogen that would also protect against a listed pathogen, are encouraged. Applications proposing development of a therapeutic against a non-listed antimicrobial-resistant pathogen are allowed; however they must focus on development of a broad-spectrum therapeutic. For these projects, applicants must clearly describe the broad-spectrum capability of the proposed candidate therapeutic.

Therapeutics projects may include, but are not limited to, one or more of the following preclinical product development activities:

• Lead optimization;
• Synthesizing, purifying, and testing lead candidates for efficacy and toxicity in model assays and preclinical in vivo systems;
• Performing preliminary pharmacokinetic and pharmacodynamic 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;
• Determination of drug/therapeutic interactions in host molecular processes;
• 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 (http://www.fda.gov/cder/regulatory/default.htm).

Vaccines for Biodefense

Vaccines are the most effective method of protecting the public against infectious diseases. This FOA will support the development of multivalent/universal vaccines and therapeutic vaccines (defined below). The development of monovalent vaccines against many listed Category A, B, or C pathogens is currently well represented within the NIAID infectious diseases research portfolio. Accordingly, candidate vaccine development supported by this FOA aligns with current HHS priorities that emphasize development of the following vaccine forms targeting Category A-C pathogens:

Multivalent/Universal Vaccines

For this FOA, 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 multivalent and universal vaccines include a universal influenza vaccine and a multivalent vaccine that protects against unrelated pathogens.

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 forms used for combination treatment of infections caused by Mycobacterium tuberculosis or Burkholderia pseudomallei.

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) (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm);
• 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.

Vaccine Technologies for Biodefense

Development of improved vaccine technologies (including adjuvants) is a high priority. Applications focused on preclinical development of technologies such as delivery platforms, antigen targeting, stability and cold-chain minimization, production characterization or formulation methodologies and lead candidate adjuvants are encouraged. Projects that would benefit production, delivery, stability and/or efficacy of non-biodefense-related vaccines are responsive provided that the proposed technology would be directly applicable to biodefense-related products. Proposed projects must pair the candidate technology with one or more appropriately mature, well-characterized vaccine(s)/antigen(s) for which models and assays exist to allow evaluation of the technology.

Vaccine technology projects may include, but are not limited to, one or more of the following activities:

• Development and/or optimization of innovative antigen production platforms;
• Development and/or optimization of innovative delivery platforms;
• Development of non-needle vaccine delivery systems, such as transdermal, intradermal, oral, sublingual, or nasal delivery;
• Development of antigen targeting technologies that enhance vaccine efficacy;
• Development of formulation methodologies that obviate the need for cold-storage of the resulting product and/or extend shelf-life;
• Improved evaluation of safety, toxicity and immunogenicity in animals;
• Improved evaluation of efficacy in challenge models where appropriate animal models are available;
• Lead candidate adjuvant optimization;
• Pre-clinical testing for safety and stimulatory capacity in animals;
• Optimization of dose and delivery platforms in preclinical evaluation;
• Optimization of production and/or characterization methodologies including process and assay development;
• Scale-up under GLP or cGMP to provide sufficient quantities for preclinical FDA-required animal studies and future Phase I clinical trials;
• Process development for the manufacturing of adjuvant components, including QA/QC methods for product recovery, characterization, purification, identity, stability etc.; and
• Performance of pre-clinical testing for safety and efficacy in animal models and other benchmarks required for successful submission and review of an IND application by the FDA (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm) or for moving into future Phase I clinical trials.

Diagnostics for Biodefense

This initiative will support development of diagnostics to rapidly identify NIAID Category A, B or C agents and their resistance profiles. Diagnostics are needed to identify infectious agents or toxins in diverse clinical samples (swabs, sputum, blood, serum, cerebrospinal fluid, urine, stool, etc.) from individuals at multiple stages of infection/intoxication. Thus, diagnostics applications must focus on detection and identification of biological threat agents in human clinical samples. Multiplexed diagnostics, as well as those able to provide diagnostic information on potential early, non-specific symptoms are particularly encouraged. Medical diagnostics that use platforms to simultaneously detect multiple agents and their drug sensitivities in clinical specimens and to rapidly distinguish whether an individual is infected/intoxicated with a biological threat agent or a common infection with similar, generalized symptoms are of high priority. It is anticipated that the medical diagnostics developed through this initiative will aid healthcare providers in diagnosing individuals exposed to and/or infected/intoxicated with aforesaid agents 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.

Features of proposed medical diagnostics:

• Rapid: Significantly shorten time to diagnosis, including shortened sample processing time;
• Sensitive: Sensitivity must be equivalent to or exceed sensitivity of FDA-cleared tests for proposed agents. If no FDA-cleared test is available for the agent(s), sensitivity must be equivalent to or exceed sensitivity of FDA-cleared tests for similar agent(s);
• Specific: Specificity must be equivalent to or exceed specificity of FDA-cleared tests for proposed agent(s). If no FDA-cleared test is available for the agent(s), specificity must be equivalent to or exceed sensitivity of FDA-cleared tests for similar agent(s);
• Easy to use: The diagnostic should be an integrated, closed sample-to-answer system with automated data analyses and output and should require minimal operator training and expertise;
• Random Access: Instrument should allow samples to be run as needed;
• Adaptable: Capable of integrating new diagnostic tests for agents as required, including detection of modified or new targets; and
• Cost-effective.

To be eligible for this FOA, applicants 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.

Diagnostic platforms/technologies projects may include, but are not limited to, one or more of the following areas:

• Use of nanotechnology, microfluidic-based systems or any other novel or innovative system to process large numbers of patient samples;
• Integrated sample-to-answer technologies for rapid, multiplexed antigen or other analyte detection using novel and improved sample processing and detection methods and reagents;
• Integrated sample-to-answer technologies capable of high throughput multiplex screening using analytes or signature biomarkers to identify human immune or other physiological response to infection;
• Integrated sample-to-answer technologies that utilize multiple methods of parallel measurements for detection in the same platform, such as detecting nucleic acids, proteins and other targets from multiple agents in the same assay;
• Technologies capable of resolving engineered or otherwise acquired genetic traits in microorganisms, such as patterns of microbial resistance or enhanced virulence;
• Methods capable of high throughput, robotics, automated data output and analyses;
• In vivo imaging methods and development of contrast reagents for visualization of pathogens or host immune responses in vivo; and
• Tests for use on human samples may consider benchmarks required for FDA approval (http://www.fda.gov/cber/devices.htm).

Applications proposing research in the following areas will be considered non-responsive and will not be reviewed:

• Applications which do not propose work on a lead candidate(s) with proof-of-concept.
• Applications from academic organizations that do not include substantive industry participation and investment.
• Applications lacking a required component of the Product Development Strategy section.
• Basic research to support the initial development of diagnostic technologies.
• Research on environmental or workplace pathogen/toxin detection technologies. Diagnostics applications must focus on detection and identification of NIAID Category A, B or C priority agents in human clinical samples.
• Applications requesting support for clinical trials.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIAID intends to commit $20 million in total costs in FY 2014 to fund 10 to 15 applications in response to this FOA.
Award Budget	Budgets for direct costs of up to $750,000 per year may be requested. In addition, applicants may request up to a total of $300,000 for major equipment in the first year of the award to ensure that research aims can be met and biohazards can be contained. Consortium F&A is not included in the direct cost limitation.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is 5 years.

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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download 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, 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 research
• 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:

Brenda Lange-Gustafson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3122, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
(express courier ZIP: 20817-7616)
Phone: (301) 451-3684
Fax: (301) 480-2408
Email: [email protected]

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions for the indicated application forms.

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 a Milestone and Timeline and a Product Development Plan component. This should be a separate attachment to Other Attachments in the Research and Related Other Project Information Component of the application (See the Application Guide SF424 Adobe Forms Version B, Section 4.4 Other Project Information Component ). The Product Development Strategy attachment must be in pdf format with a filename of Product_Development_Strategy.pdf. Applications lacking a required component of the Product Development Strategy section will be deemed non-responsive and will not be reviewed. The overall Product Development Strategy is limited to 12 pages. (Note: Applicants should not add attachments in the Research and Related Other Project Information Component 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).
• Titles, abstracts, and status of patents and patent applications that are relevant to the project and are owned or licensed by the applicant.

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 biodefense/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 therapeutic, vaccine, or vaccine technology projects should summarize:

• The performance specifications and features the product should have in order to provide immunological and/or therapeutic benefit (vaccine, therapeutic or adjuvant) or clinical, manufacturing and/or economic benefit (vaccine technology).
• 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.

Support for industrial partner activities may be included in the project budget.

Requested budgets must include funds for travel by the PD/PI and key personnel to an annual meeting in Bethesda, Maryland (USA), or to a relevant scientific meeting, as determined by NIAID Program staff, at which the NIAID Program Official will be present.

Equipment: Applicants may request up to a total of $300,000 for major equipment to ensure that research aims can be met and biohazards can be contained. Funds for equipment must be included in the first year requested budget with justification, and are in addition to the $750,000 direct cost limit. Unapproved equipment requests that exceed $300,000 will not be considered for funding.

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

Research Strategy

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: All applications submitted by academic organizations must demonstrate substantive investment and participation in the project by at least one industry participant.

Select Agent Research

In addition to addressing select agent requirements, applicants must address issues related to physical or facility security and biocontainment and biosafety pertinent to the specific agent(s) of interest. Guidance on appropriate biocontainment and biosafety measures can be found in the Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition as found on the CDC website: http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm. Guidelines for Institutional Biosafety Committees are available at: http://oba.od.nioih.gov/rdna_ibc/ibc.html.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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.

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.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application before the deadline 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.

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.

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 (SAM). 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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

A mandatory 1 day progress review meeting will be held annually at the NIAID, or at a site designated by the NIAID Program Official, during which the Program Director/Principal Investigator and appropriate Key Personnel will present project accomplishments. Requested budgets must include funds for travel by the Program Director/Principal Investigator and key personnel to an annual meeting in Bethesda, Maryland (USA), or to a relevant scientific meeting, as determined by NIAID Program staff, at which the NIAID Program Official will be present. A critical determinant of success will be the degree of communication between the PD/PI, Project Leaders and other significantly involved parties. Therefore, in addition to the one meeting listed above, additional meetings, which may be necessary for coordination of project activities, may be scheduled, if justified. Regular telephone and written communication with the NIAID Program Official is considered to be very important and is strongly encouraged.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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 or diagnostic against one or more of the specific biologic threat agents identified in this initiative? If the aims of the application are achieved, are important biomedical agents or products likely to result?

Investigator(s)

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? Do the regulatory personnel possess the appropriate expertise to guide cGMP manufacture and/or related processes (if applicable)?

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? Does the research proposed in each project leverage multi-disciplinary involvement to accelerate therapeutics or diagnostics product development, many aspects of which may not be inherently innovative? In addition, does the approach represent the best use of current or emerging technologies and appropriate collaborations to achieve the research objectives?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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.

Product Development Strategy

Does the Product Development Strategy adequately address the specific Research Goals and Objectives described in the FOA? Are the Milestones appropriate and feasible? Is the proposed Product Development Plan feasible and appropriate for proposed and future product development? Is the Plan consistent with achieving the goals of this program?

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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.

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 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) Genome Wide Association Studies (GWAS).

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.

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.

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Michael R. Schaefer, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Phone: 301-451-3758
Email: [email protected]

Brenda Lange-Gustafson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Phone: 301-451-3684
Email: [email protected]

Cassandra L. Fields
National Institute of Allergy and Infectious Diseases (NIAID)
Phone: 301-594-6355
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.