Part I Overview Information

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Department of Health and Human Services

Issuing Organization
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov)

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov)

Title: Partnerships for Biodefense Food- and Water-borne Diseases (R01)

Announcement Type
New

Request for Applications (RFA) Number: RFA-AI-09-027

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.856

Key Dates
Release/Posted Date: June 24, 2009
Opening Date: August 24, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): August 24, 2009
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): September 23, 2009
Peer Review Date(s): January, 2010
Council Review Date(s): May, 2010
Earliest Anticipated Start Date(s): July, 2010
Additional Information To Be Available Date (Activation Date): http://www.niaid.nih.gov/ncn/budget/partnerships.htm
Expiration Date: September 24, 2009

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

• 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 development of therapeutics, immunotherapeutics, medical diagnostics and broad-spectrum vaccines for NIAID Category B food- and water-borne priority pathogens and toxins (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/CatA.htm).
• Mechanism of Support. This FOA will utilize the R01 grant mechanism.
• Funds Available and Anticipated Number of Awards. The NIAID intends to commit $7.3 million in total costs in FY2010 to fund five to ten applications in response to this FOA. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.
• Budget and Project Period. The annual direct costs that can be requested may not exceed $750,000 without prior approval by program staff. Requested budgets must be justified by the proposed research and will be evaluated by the review panel and program staff. The total project period for an application submitted in response to this funding opportunity may not exceed 5 years.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Include Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are not permitted in response to this FOA.
• Special Application Requirements. See Section IV.6 (Other Submission Requirements and Information) for special application requirements.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials.
• General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
• SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
• General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

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 select pathogens and toxins.

Through this FOA, the NIAID invites research applications for projects that will lead to development of new and/or novel therapeutics, immunotherapeutics, medical diagnostics, or broad spectrum vaccines focused on the following NIAID Category B food- and water-borne priority pathogens and toxins:

Bacteria

• Diarrheagenic Escherichia coli
• Pathogenic vibrios
• Shigella species
• Salmonella
• Listeria monocytogenes
• Campylobacter jejuni
• Yersinia enterocolitica

Viruses

• Caliciviruses
• Noroviruses)

Protozoa

• Cryptosporidium parvum
• Toxoplasma gondii

Toxins

• Staphylococcus enterotoxin B
• Clostridium perfringens epsilon toxin

Research may include, but is not limited to: target identification and/or validation; adaptation of products or platform technologies to biodefense applications; development of broad spectrum platforms and/or production technologies; optimization of products; process development; preclinical evaluation; scale-up; and production of quantities sufficient for preclinical regulatory requirements. Applications that include collaborations between researchers from different disciplines and/or with industry are strongly encouraged.

The NIAID recognizes that the inherent nature and demands of the product development process may require funding large, complex grants with interdependent specific aims. Furthermore, some aspects of the product development process (e.g., Good Laboratory Practice [GLP] or current Good Manufacturing Practice [cGMP] production) are inherently not innovative. Research projects funded under this FOA will be implemented in accordance with the defined project goals, interim objectives/development milestones, and the timeline for the achievement of goals and milestones. Knowing that product development is often an iterative and sequential process, and that steps early in the process may not be successful and may need to be modified or reworked, NIAID staff will be actively involved in evaluating the milestones of awardees and determining whether continued investment in the development is warranted. When appropriate, research projects funded under this FOA will incorporate measures that are consistent with the guidelines that govern Good Laboratory Practice (GLP as defined by 21 CFR(58)) and current Good Manufacturing Practice (cGMP as defined by 21 CFR(211)).

Partnerships

A key component of this initiative is the formation of collaborative partnerships between academic researchers from different disciplines or with industry. For the purpose of this FOA, "industry" is defined as large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, and chemical companies. Since academic organizations are often the source of new candidate products, this FOA will also support a partnership between industry and collaborator(s) as necessary from academic (or non-profit) research organizations. For this FOA, partnerships are strongly encouraged, but not required. The Principal Investigator of the project may be affiliated with industry, an academic organization or non-profit research organization.

Applications submitted to this FOA will include a Product Development Plan (PDP) to assist reviewers and program staff in project evaluation. The PDP will define the general goals of the project, intended use/indication of the proposed therapeutic or diagnostic, and biodefense/public health gap the product is intended to fill. Additionally, the PDP will detail the stage-specific product development activities that will be performed during the project period and outline plans for further development after completion of the project.

Background

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 pathogens and toxins list. The initial NIAID Strategic Plan for Biodefense Research (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/strategic_plan.htm) was published in 2002 and followed by research agendas for and Category B and C agents (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/categorybandc.htm). In 2007, the DHHS Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) published an Implementation Plan (http://www.hhs.gov/aspr/barda/phemce/enterprise/strategy/index.html), outlining strategies for identifying medical countermeasure requirements and establishing priorities for their research, development and acquisition.

NIAID recently published an updated Strategic Plan for Biodefense Research (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/biosp2007.pdf) that is consistent with the DHHS PHEMCE Implementation Plan and related components of the national biodefense strategy. The updated plan continues to focus on translation of basic research to product development, but with an emphasis shift from the current 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.

Research Goals and Objectives

To meet the objectives outlined in the updated NIAID Strategic Plan for Biodefense Research, it is imperative that promising findings/technologies are translated rapidly into new approaches and strategies for product development. The involvement of experts from diverse disciplines (e.g., biochemists, structural biologists, protein chemists, pharmacologists, immunologists, molecular biologists, engineers and clinicians) within academia and industry is needed to enable development of well-designed candidates for therapeutics, immunotherapeutics, medical diagnostics, and vaccines.

The objective of this FOA is to support research that will advance the development and/or production of countermeasures (therapeutics, immunotherapeutics, medical diagnostics, and broad spectrum vaccines) for the NIAID Category B food- and water-borne bacteria, viruses, protozoa and toxins listed above. Developmental research is not required to result in a "final" product, but must advance the development of a candidate product. Applications that focus on development of existing candidate products [e.g., lead compound(s)] are encouraged. A second objective of this FOA is to stimulate scientifically sound, original, and innovative research requiring a comprehensive team and multidisciplinary effort that will facilitate advancement of a promising candidate product through the product development pathway.

NOTE: While clinical development strategies may be included within an overall product development plan, this FOA will NOT support Phase I, II, and III clinical trials or field trials. Thus, applications requesting support for clinical trials will be viewed as unresponsive and will not be reviewed. However, utilization of appropriate human cell lines and human derived material in pre-clinical studies in support of complying with regulatory requirements is considered responsive and is encouraged.

NOTE: Applications proposing the development of broad spectrum therapeutics, multiplex diagnostics, or broad spectrum vaccines that do not focus on a listed NIAID Category B food- and water-borne priority pathogen or toxin will be deemed unresponsive and will not be reviewed.

NOTE: This FOA will NOT support research on environmental or workplace detection technologies or targets. Diagnostics applications must focus on detection and identification of one or more NIAID Category B food- and water-borne priority pathogen listed above.

NOTE: Where relevant, projects may include performing pre-clinical 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/cber/vaccine/vacappr.htm).

Therapeutics for Food- and Water-borne Pathogens

Development of safe and effective antimicrobials against biodefense agents and emerging pathogens is a high priority. The updated 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 agents. Applications for development of either a broad spectrum anti-infective against multiple NIAID Category B food- and water-borne pathogens or a non-listed pathogen that would also protect against multiple listed NIAID Category B food- and water-borne agents are encouraged. Also of interest are strategies to overcome antibiotic resistance in order to extend the clinical utility of existing broad spectrum antimicrobials.

Applications for development of new therapeutics against targeted NIAID Category B priority food- and water-borne pathogens or toxins are invited. Therapeutics targeting pathogens for which no standard clinical treatment exists (e.g., eradication of parasitic brain cysts in the immunosuppressed) are also of interest. Therapeutics projects may include, but are not limited to, one or more of the following areas:

Identification and validation of new targets for drug discovery or development of previously identified targets for drugs by examining microbial gene products expressed during infection and/or host gene products expressed as a consequence of infection;

Identification and validation of new targets for drug discovery focused on host-directed components that enable infection;

Identification and validation of novel therapeutics that do not promote the acquisition or selection of microbial resistance mechanisms;

Performing molecular modeling, library screening, and medicinal chemistry/structural activity analysis to optimize candidate compounds for preclinical studies;

Performing reiterative design, chemical synthesis and in vitro analysis to develop a "mature" lead compound;

Synthesis of sufficient quantities of candidate drug for in vitro analysis and/or exploration of the use of active components of natural products as potential drug sources for development;

Process development for the manufacturing of drugs, including QA/QC, methods for product recovery, characterization, purification, identity, stability, etc.;

Synthesis of sufficient quantities of a lead compound(s) for further characterization, including efficacy and toxicity in in vitro or in vivo models;

Evaluation of the potential for the emergence of drug resistance in model systems;

Performing preliminary pharmacokinetic and pharmacodynamic analyses;

Assessing bioavailability and mechanism of action;

Synthesizing, purifying, and testing drugs/inhibitors for efficacy and toxicity in model assays and preclinical in vivo systems;

Determination of drug interactions in host molecular processes; and

Performing required benchmarks for moving a drug candidate into Phase I clinical trials (http://www.fda.gov/cder/regulatory/default.htm).

Immunotherapeutics for Food- and Water-borne Pathogen

Applications to discover and/or improve immune-based therapeutics including both broad-spectrum (innate immunity) and pathogen or toxin-specific (antibodies) are invited. Major objectives for products generated in this research program include prevention of infection or intoxication in the face of an immediate threat, protection of immunocompromised individuals, and post-exposure treatment to suppress infection and disease. Projects focused on compounds that directly affect pathogens/toxins and/or approaches to stimulate non-specific immunity are encouraged. 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. Projects may include, but are not limited to, one or more of the following areas:

Innate immunity:

Discovery and characterization of novel antimicrobial peptides, lectins, or immune modulators with broadly protective potential;

Development of candidate compounds to optimize in vivo activity, including improving the therapeutic index and specificity for targeted NIAID Category B food- and water-borne priority pathogens;

Testing and validation of efficacy in in vitro or in vivo models (e.g., rodents, nonhuman primates);

Process development for the manufacturing of product, including QA/QC, methods for product recovery, characterization, purification, identity, stability, etc.;

cGMP production to generate sufficient product to conduct pre-clinical studies and Phase I clinical studies; and

Preclinical testing for safety and efficacy in animal models.

Antibodies:

Discovery and characterization of novel antibodies with high specificity for pathogen antigens or toxins;

Methods to modify existing reagents to improve economy of production, half-life in vivo, affinity for target antigens, neutralization potency, microbial clearance rates, or tissue accessibility; or to decrease adverse side effects of administration (e.g. improved purification methods, production of humanized or fully human antibodies);

Process development for the manufacturing of antibody product, including QA/QC methods for product recovery, characterization, purification, identity, stability etc.;

cGLP or cGMP production to generate sufficient product to conduct pre-clinical and Phase I clinical studies; and

Preclinical testing for safety and efficacy in animal models.

Diagnostics for Food- and Water-borne Pathogens

There is a need for rapid, sensitive, specific, easy to use, adaptable, and cost-effective medical diagnostics for public health laboratories, hospital-based clinical laboratories, and point-of-care (POC) use to diagnose individuals exposed to and/or infected with Category B food- and water-borne priority pathogens or toxins. Diagnostics are needed to identify and differentiate multiple infectious agents or toxins in clinical samples (swabs, blood, serum, stool, etc.) from individuals that are pre-symptomatic, symptomatic, or have non-specific symptoms so appropriate therapeutic intervention or containment can be executed.

Product development for POC diagnostic technologies should encompass development of new or improved methods, tools, or devices for sample collection, processing, and detection that are operational in a variety of settings, which include the home, rural and urban community public health care clinics, and temporary health care clinics established in response to a natural or man-made disaster. Medical POC diagnostics that simultaneously and rapidly distinguish whether an individual is infected by a specific infectious agent and/or determine drug sensitivities in clinical specimens are of high priority. Research areas include, but are not limited to, development of new or improved self-collection methodology (e.g., rectal swabs, stool samples, etc.), public health-based POC diagnostic testing, and home-based test kits. Examples include single unit swab and fluid processing; non-sterile collection devices with preservation capability; and integrated collection, processing and detection methods.

Applications for applied research through advanced product development for medical diagnostics, including both technology and development of tests specific for the listed Category B food- and water-borne pathogens or toxins are invited. It is anticipated that the medical diagnostics developed through this initiative will be used on human samples to aid in diagnosing individuals exposed to and/or infected with Category B food- and water-borne priority pathogens or toxins and will be developed with the eventual and ultimate goal of obtaining FDA-clearance. However, this need not be the final result of the proposed research project period.

Medical diagnostics ideally will be:

Rapid: Proposed diagnostic test time of 30-45 minutes, which includes the time required to process the clinical sample through detection and determination of diagnostic test result. It is expected that prototypes will have longer test times.

Sensitive: Sensitivity must be equivalent to or exceed sensitivity of FDA-cleared tests for proposed pathogen(s) and/or their toxins. If no FDA-cleared test is available for the pathogen and/or their toxin, sensitivity must be equivalent to or exceed sensitivity of FDA-cleared tests for similar types of pathogen(s) and/or their toxins;

Specific: Specificity must be equivalent to or exceed specificity of FDA-cleared tests for proposed pathogen(s) and/or their toxins. If no FDA-cleared test is available for the pathogen and/or their toxin, specificity must be equivalent to or exceed sensitivity of FDA-cleared tests for similar types of pathogen(s) and/or their toxins;

Easy to use: The final medical diagnostic should be an integrated, closed sample-to-answer system that requires minimal operator training and expertise;

Accessible: Test, device, or instrument should allow samples to be run as needed;

Cost-effective, and;

Adaptable: Capable of integrating new diagnostic tests for pathogens and/or toxins as required.

Projects may include, but are not limited to, one or more of the following areas:

Operational capacity in a variety of health care settings including home, rural and urban community public health care clinics, and temporary health care clinics (e.g., those established in response to a natural or man-made disaster);

Innovative and/or improved methods for rapid sample preparation, collection, processing, and if appropriate, concentration;

Technologies demonstrating the highest performance of specificity, sensitivity, rapidity, and cost-effectiveness when applied to sample collection and testing from the gastrointestinal tract;

An easy-to-interpret readout;

Technologies that integrate multiple methods of parallel measurement for detection, such as detecting nucleic acids, proteins and other targets from multiple agents in the same assay;

Technologies for multiplex, rapid antigen, nucleic acid, or other analyte detection using novel and improved sample processing, detection methods, and reagents;

Technologies capable of resolving engineered or otherwise acquired genetic traits in microorganisms, such as patterns of microbial resistance or enhanced virulence;

Technologies that are operational in infrastructure poor settings (e.g., no electricity or clean water);

Process development for the manufacturing of diagnostic components, including QA/QC methods for characterization, purification, identity, and stability;

Tests for use on human samples that are considered benchmarks required for FDA approval (http://www.fda.gov/cber/devices.htm);

Integrated sample-to-answer technologies capable of high throughput multiplex screening using analytes (nucleic acid, protein, etc.) or signature biomarkers to identify human immune or other physiological response to infection;

Methods capable of high throughput, robotics, and 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

Integration and validation of Internal Process controls for sample-to-answer technologies.

NOTE: This FOA will NOT support research on environmental or workplace detection technologies or targets. Diagnostics applications must focus on clinical detection and identification of one or more NIAID Category B food- and water-borne priority pathogens listed above.

Broad-spectrum Vaccines for Food- and Water-borne Pathogens

Vaccines are the most effective method of protecting the public against infectious diseases. The updated NIAID Strategic Plan for Biodefense Research emphasizes development of broad spectrum vaccines against biological threat agents. Vaccines characterized by broad spectrum activity include cross-protective forms, which induce an immune response against constant components of a microbe, and multiple component forms, which include elements that protect against microbes that are different, but closely related. Applications for development of broad spectrum vaccines that protect against multiple NIAID Category B food- and water-borne pathogens or toxins are the focus of the vaccine component of this FOA.

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

Evaluation of vaccine candidates, formulated with or without adjuvants or immunomodulators, against multiple NIAID Category B food- and water-borne priority pathogens or toxins;

Identification and validation of protective epitopes for the development of recombinant, subunit, multi-component or cross-protective vaccine candidates;

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 pre-clinical and early clinical evaluation;

Optimization of dose and route of delivery in pre-clinical evaluation;

Evaluation of safety, toxicity and immunogenicity in animals;

Evaluation of efficacy in challenge models where appropriate animal models are available;

Optimization of production methodology including process development;

Scale up and production of candidate vaccines including cGMP production, and;

Development of formulation methodologies that obviate the need for cold-storage of the resulting product and/or extend shelf-life.

NOTE: Applications proposing the development of a vaccine against a single toxin or pathogen (species) will be deemed unresponsive and will not be reviewed.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

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1. Mechanism of Support

This FOA will use the R01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

The estimated amount of funds available for support of 5-10 projects awarded as a result of this announcement is $7.3M for fiscal year 2010. Future year amounts will depend on annual appropriations. An applicant may request a project period of up to 5 years.

The annual direct costs that can be requested may not exceed $750,000. Requested budgets must be justified by the proposed research and will be evaluated by the review panel and program staff. NIAID recognizes that some developmental projects with advanced components (GMP production, pre-clinical evaluation in non-human primates, etc.) may require annual direct costs exceeding $750,000. For such projects, applicants may seek prior approval by program staff to request annual direct costs greater than $750,000. NOTE: Applications with unapproved direct costs greater than $750,000 in any year will be deemed non-responsive and will not be reviewed.

Applicants may request up to a total of $300,000 in first-year costs for major equipment to ensure that research aims can be met and biohazards can be contained. Prior approval from program staff, listed below under Section VII. Agency Contact(s) must be obtained for requests for equipment that exceed this amount. Unapproved equipment requests that exceed $300,000 will not be considered for funding.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• 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
• 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)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI 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.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.

Resubmissions. Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewals. Renewal applications are not permitted in response to this FOA.

Section IV. Application and Submission Information

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To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/applicants/get_registered.jsp) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual(s) designated as PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
• Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
• When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
• This registration/affiliation must be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PD(s)/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY: (301) 451-5936

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., Special Instructions, regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic [non-U.S.] Entities)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

• Request budgets in U.S. dollars;
• Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component)(see NOT-OD-06-096);
• Not include any charge-back of customs and import fees;
• If appropriate, request funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) ( see NOT-OD-01-028, March 29, 2001);
• Comply with Federal/NIH policies on human subjects, animals, and biohazards; and
• Comply with Federal/NIH biosafety and biosecurity regulations (see Section VI.2., Administrative and National Policy Requirements )

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan [Section 14 of the Research Plan Component in the SF424 (R&R)], must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review and Anticipated Start Dates
Opening Date: August 24, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): August 24, 2009
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): September 23, 2009
Peer Review Date(s): January 2010
Council Review Date(s): May 2010
Earliest Anticipated Start Date(s): July 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Dr. Gregory Jarosik
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3117, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 496-0695
Fax: (301) 480-2408
Email: [email protected]

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

• If everything is acceptable, no further action is necessary. The application will automatically move forward to the Division of Receipt and Referral in the Center for Scientific Review for processing after two weekdays, excluding Federal holidays.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if it is determined that some part of the application was lost or did not transfer correctly during the submission process, the AOR/SO will have the option to Reject the application and submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to ensure that the issues are addressed and corrected. Once rejected, applicants should follow the instructions for correcting errors in Section 2.12, including the requirement for cover letters on late applications. The Reject feature should also be used if you determine that warnings are applicable to your application and need to be addressed now. Remember, warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two weekdays if no action is taken. Some warnings may need to be addressed later in the process.
• If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement.

6. Other Submission Requirements

RESEARCH PLAN

1. Research Focus

Applicants are encouraged to read the updated NIAID Strategic Plan for Biodefense Research (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/biosp2007.pdf) before preparing an application. This program supports development of new and promising products for biodefense. Each application must propose a research and development project whose goal is to develop and/or advance a countermeasure (vaccine, adjuvant, therapeutic, immunotherapeutic or diagnostic) or vaccine technology, specific for one or more NIAID Category B food- and water-borne priority pathogens listed above. It is not necessary to propose to complete the product development process up to the point of readiness for clinical trials within the time frame of this project. Applications that would significantly advance a specific product toward clinical or field usefulness are responsive.

NOTE: Applications for development of a broad spectrum vaccine or therapeutic against a non-listed pathogen or toxin that would protect against a listed NIAID Category B food- or water-borne pathogen or toxin MUST include in the Research Plan:

• Identification of the targeted NIAID Category B food- or water-borne pathogen or toxin and a clear justification of the research approach; and
• Early and ongoing experiments to validate the efficacy of the candidate vaccine or therapeutic against a virulent form of the targeted NIAID Category B food- or water-borne pathogen or toxin.

NOTE: All applications for research projects focused on diagnostics should include in the Research Plan:

• 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.

2. Mandatory Meetings

One mandatory progress review meeting will be held annually at the NIAID, or at a site designated by the NIAID Program Official, during which the Principal Investigator and appropriate Key Personnel will present project accomplishments. Requested budgets must include funds for travel by the 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. The NIAID Program Official and External Advisors (when applicable) will be present. A critical determinant of success will be the degree of communication between the Principal Investigator, 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.

3. Major 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. Prior approval from program staff, listed below in Section VII. Agency Contact(s), must be obtained for requests for equipment that exceed this amount. Unapproved equipment requests that exceed $300,000 will not be considered for funding.

4. Good Laboratory and Good Manufacturing Practices

When appropriate, applicants must document in the Research Plan 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.

ADDITIONAL SUBMISSION REQUIREMENTS (DO NOT COUNT TOWARDS PAGE LIMITS FOR RESEARCH PLAN)

1. 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 is not included in the 25-page limit of the Research Plan. The Milestones and Timeline must be included as an attachment to the Research & Related Other Project Information form under item 11 Other Attachments. The Milestones and Timeline section 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).
• Patent status or other protection of project intellectual property.

2. Product Development Plan

Applicants are required to include an add-on section entitled Product Development Plan in the application to assist reviewers and program staff in project evaluation. This section must be no more than 5 pages and is not included in the 25-page limit of the Research Plan. The Product Development Plan must be included as an attachment to the Research & Related Other Project Information form under item 11 Other Attachments. The Product Development Plan should follow the Milestones and Timeline 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 product profile that is defined by licensing indication is not requested.

Additionally, the Product Development Plan must include descriptions pertaining to early-stage and/or mid-stage-specific product development activities, as applicable, detailed below. Applications for projects that span early-stage and mid-stage should include the relevant information requested for both activities.

Early-Stage Product Development Projects

For the purpose of this RFA, early-stage is defined as all activities leading to and including lead candidate identification (vaccines, therapeutics, or adjuvants) or identification of clinical diagnostic targets and development of assays to detect these targets or initial development of diagnostic platform technology (diagnostics).

Product Development Plans for early-stage projects should include:

• A detailed description of the qualitative and quantitative criteria and data elements to be used to assess the scientific merit of feasibility or proceeding to the next stage of development.
• A description of the distinct stages/activities that are gates for Go/No Go decisions for advancing to the next stage.

Mid-Stage Product Development Projects

For the purpose of this RFA, mid-stage is defined as all activities beyond lead candidate identification (e.g. safety evaluation, stability testing, manufacturing, development, etc.), diagnostic assay development, or initial development of diagnostic platform technology.

Product Development Plans for mid-stage vaccine, therapeutic or adjuvant 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 to support the characterization and selection of the candidate product for further development. Specifically, a summary of data that demonstrates efficacy in appropriate animal models and assays against one or more of the selected pathogens is required. 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.

Product Development Plans for mid-stage 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 pathogen(s) and/or toxin(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 pathogen concentrations, different sites). If no FDA-cleared test is available for the pathogen(s) and/or toxin(s), the specifications should be equivalent to or exceed performance specifications of FDA-cleared tests for similar types of pathogen(s) and/or toxin(s).
• Data to support the usefulness of the candidate product for selection 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.

NOTE: Applications lacking a free-standing and detailed Product Development Plan will be deemed unresponsive and will not be reviewed.

3. Physical and/or Facility Security

Applicants must address issues related to physical or facility security and biocontainment and biosafety (http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm) pertinent to the specific pathogens of interest in an add-on section entitled Biosafety and Biocontainment . Guidelines for Institutional Biosafety Committees are available at: http://www4.od.nih.gov/oba/IBC/IBCindexpg.htm. This section must be no more than 1 page and is not included in the 25-page limit of the Research Plan. The Biosafety and Biocontainment section must be included as an attachment to the Research & Related Other Project Information form under item 11 Other Attachments and should follow the Product Development Plan.

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

Page limitations of the PHS398 Research Plan component must be followed as outlined in the SF424 (R&R) Application Guide. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Section V. Application Review Information

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1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• 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 impact/ priority score;
• Receive a written critique; and
• Receive a second level of review by the National Advisory Allergy and Infectious Disease Council.

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

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

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority 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 five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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 vaccine, adjuvant, 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/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, 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, immunotherapeutics, and 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? Are the proposed objectives/milestones appropriate and feasible? Is the proposed product development plan feasible and appropriate for future product development?

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?

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the 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.

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.

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.

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

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.

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

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

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).

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.

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 (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.htm); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

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1. Award Notices

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 NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Dr. Melody Mills
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 1303, MSC-6604
6610 Rockledge Drive
Bethesda, MD 20892-6604
Telephone: (301) 435-2876
FAX: (301) 402-1456
E-Mail: [email protected]

Dr. Michael Schaefer
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 5003, MSC-6604
6610 Rockledge Drive
Bethesda, MD 20892-6604
Telephone: (301) 451-3758
FAX: (301) 480-1263
E-Mail: [email protected]

2. Peer Review Contact(s):

Dr. Gregory Jarosik
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3117, MSC 7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 496-0695
Fax: (301) 480-2408
Email: [email protected]

3. Financial/Grants Management Contact(s):

Cassandra Fields
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2245, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20817-7614
Telephone: (301) 594-6355
Fax: (301) 493-0597
Email: [email protected]

Section VIII. Other Information

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Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants ( NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.