Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Partnerships for Diagnostics to Address Antimicrobial Resistance of Select Bacterial Pathogens (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. March 27, 2014 - See Notice NOT-AI-14-044. Notice of Change to Research Objectives.
Funding Opportunity Announcement (FOA) Number	RFA-AI-14-019
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	The purpose of this Funding Opportunity Announcement (FOA) is to solicit research applications for projects focused on development and/or production of diagnostics that will enable rapid, sensitive, specific, culture-independent detection of high-priority antimicrobial-resistant Gram-negative bacterial pathogens. This FOA is focused on select healthcare-associated bacteria where resistance compromises effective treatment, including: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and extra-intestinal pathogenic Escherichia coli. Applications must include a Product Development Strategy and demonstrate substantive participation by at least one industrial participant.

Posted Date	March 12, 2014
Open Date (Earliest Submission Date)	May 19, 2014
Letter of Intent Due Date(s)	May 19, 2014
Application Due Date(s)	June 19, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October 2014
Advisory Council Review	January 2015
Earliest Start Date	April 2015
Expiration Date	June 20, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

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

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit research applications for projects focused on development and/or production of medical diagnostics that permit rapid species identification, and optimally, corresponding antibacterial susceptibility profiles for one or more of the following causes of antibacterial-resistant infections in hospital settings: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and extra-intestinal pathogenic Escherichia coli. The primary goal of such diagnostics is to facilitate antibacterial stewardship, thereby reducing selective pressure and improving patient outcomes. A secondary goal, centered on increasing treatment options, is to facilitate enrollment in clinical trials for new antibacterial therapeutics against these pathogens. The proposed diagnostic must be designed to detect the target pathogen(s) in normally sterile sample types, such as blood, cerebral spinal fluid (CSF), and pleural fluid, but may also include the detection of the target pathogen(s) in the context of non-sterile sample types, such as those analyzed for hospital- and/or ventilator-associated pneumonia (HAP/VAP). The proposed diagnostic platforms and/or technologies must be supported by proof-of-concept data demonstrating feasibility. Examples of research areas supported include, but are not limited to: assay/prototype development; sample preparation; development of broad-spectrum platforms and/or production technologies; adaptation of products or platform technologies to new applications; optimization of products or technologies; process development; manufacturing; and diagnostic validation.

Industrial Participation

All applications submitted to this FOA by academic organizations must demonstrate substantive investment and participation in the project by at least one industry participant. For the purpose of this FOA, "industry" is defined as large or small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, and/or chemical companies, or non-profit agencies with demonstrated experience in product development. Substantive investment" is defined as a commitment of one or more resources including, but not limited to: product/prototype development support/guidance, personnel, in kind contributions of materials and/or reagents [i.e., chemical libraries, innovative biotechnology platforms, scale up of Good Manufacturing Process (cGMP) chemical synthesis or production, etc.], provision of animal or other laboratory models for evaluation, subcontracts, data management resources or regulatory support. Support for industrial partner activities may be included in the project budget. The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of the project may be affiliated with either an academic organization or industry. Applications submitted by industrial institutions or product development non-profit agencies do not require an additional partner.

Background

Escalating resistance to antibacterial agents is an increasing contributor to morbidity, mortality, and rising healthcare costs. Emerging pan-drug resistance has been documented for a subset of hospital-associated infections, such as those caused by the Gram-negative pathogens Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and extra-intestinal pathogenic Escherichia coli. The emergence of these untreatable infections highlights the importance of antimicrobial stewardship and the need to develop new therapeutics against the causative pathogens. Development of rapid and informative diagnostics will help address this growing public health challenge by allowing clinicians to quickly determine the most effective treatment for infected individuals and will facilitate antimicrobial stewardship by reducing the empiric use of broad-spectrum antimicrobials. Additionally, such diagnostics would benefit development and approval of new antibacterials by reducing the diagnostic uncertainty that necessitates enrollment of large numbers of patients who may not be evaluable in pivotal efficacy trials. Hence, rapid diagnostics should provide a means to reduce the size and cost of antibacterial clinical trials. Accordingly, development of new diagnostics that will enable enrichment of evaluable subjects in therapeutic clinical trials are of particular interest. An FDA Draft Guidance released in July 2013 provides information related to the development of diagnostics for this use (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM359184.pdf). It is expected that proposed diagnostics will be developed with the ultimate goal of obtaining FDA clearance; however such clearance need not be the final result of the proposed research project.

Research Objectives

The objective of this FOA is to solicit research that will advance the development and/or production of diagnostics that will enable rapid, sensitive, specific, culture-independent species identification of key Gram-negative hospital-associated pathogens (listed below). Priority will be given to diagnostics that additionally provide corresponding antibacterial susceptibility profiles for the targeted pathogen(s). Each application must propose a research and development project whose goal is to advance a diagnostic platform/technology. Research projects are not required to result in a "final" product. Moreover, it is not necessary to propose to complete the product development process up to the point of readiness for validation within the time frame of the project. Applications for projects that would significantly advance a candidate diagnostic product/platform toward clinical utility are responsive and encouraged.

Applications must include plans to detect one or more of the following Gram-negative bacteria pathogens:

• Klebsiella pneumoniae,
• Acinetobacter baumannii
• Pseudomonas aeruginosa
• Enterobacter species
• Extra-intestinal pathogenic Escherichia coli

Diagnostic platforms/technologies intended for differential diagnosis and/or clinical decision making must incorporate multiple bacterial targets, including at least one of the Gram-negative species listed above and may include diagnosis of additional pathogens. Detection of host factors predictive of bacterial infection that may provide clinically actionable information may also be included. A proposed diagnostic intended solely to facilitate clinical trial enrollment for a pathogen-specific drug may target a single Gram-negative species from the above list and optimally would report antibacterial susceptibility profiles.

The proposed diagnostic technologies must detect the target pathogen(s) from at least one normally sterile specimen type, such as blood, CSF, or pleural fluid. Focusing on these sample types will allow validation of the technology in a setting where colonizing organisms are not a complicating factor. There are a number of other types of hospital-associated infections where rapid diagnostics are also needed, but where the presence of commensal/colonizing organisms makes interpretation of test results difficult. Therefore, applications may also include plans to include detection of the target pathogen(s) in non-sterile sample types such as those analyzed for HAP/VAP; for such plans, applicants must specify how contamination with colonizing organisms will be addressed.

For the purposes of this FOA, the following test characteristics are of greatest importance:

• Rapid: Proposed diagnostic test time of < 3 hours for clinical diagnostics that identify species and resistance profile information or < 1 hour for clinical trial enrichment tools, which includes the time required to process the clinical sample (if appropriate) through detection and final test result;
• Culture-independent: the diagnostic should focus on direct detection of the target pathogen(s) from normally sterile samples;
• Sensitive: sensitivity should be equivalent to or exceed sensitivity of FDA-cleared tests for proposed agent(s) from the same sample type; and
• Specific: specificity should be equivalent to or exceed specificity of FDA-cleared tests for proposed agent(s) from the same sample type.

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

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

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

• Use of nanotechnology, microfluidic-based systems or any other novel or innovative system to process large numbers of patient samples;
• Integrated sample-to-answer technologies for rapid, multiplexed antigen or other analyte detection using novel and improved sample processing and detection methods and reagents;
• Integrated sample-to-answer technologies capable of high throughput multiplex screening using analytes or signature biomarkers to identify human immune or other physiological response to infection;
• Technologies capable of detecting drug-resistance/drug-susceptibility, relevant to clinical decision making;
• Technologies and capacity for high throughput, automated data management, output and analyses; and
• In vivo imaging methods and development of contrast reagents for visualization of pathogens or host immune responses in vivo.

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

NOTE: The following application types will be considered non-responsive and will not be reviewed:

• Applications proposing development of a diagnostic that lacks the required capability to detect at least one of the following pathogens: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and extra-intestinal pathogenic Escherichia coli.
• Applications proposing the development of a diagnostic that lacks the required capability to detect the specified pathogen from a normally sterile site, such as blood, CSF, or pleural fluid.
• Applications lacking proof-of-concept data for proposed diagnostic platforms/technologies.
• Applications that do not have the ultimate goal of detection and identification of pathogens in human clinical samples, or those which are focused on development of environmental or workplace pathogen/toxin detection technologies.
• Applications that propose clinical trial(s). While clinical development strategies may be included within an overall project, this FOA will NOT support clinical trials. Utilization of human-derived material in pre-clinical studies in support of compliance with regulatory requirements is permitted and encouraged.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $12 million in FY 2015 to fund 10 - 15 awards.
Award Budget	Budgets for direct costs of up to $750,000 per year may be requested. In addition, applicants may request up to a total of $300,000 for major equipment in the first year of the award to ensure that research aims can be met and biohazards can be contained. Consortium F&A is not included in the direct cost limitation.
Award Project Period	The scope of the proposed project should determine the project period. The maximum period is 5 years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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

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

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

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

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

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

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

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

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

• Applications from academic organizations must include substantive industry participation and investment.

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

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

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

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

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

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

The letter of intent should be sent to:

Dr. Nancy Lewis Ernst
National Institute of Allergy and Infectious Diseases
6700B Rockledge Drive Room 3135
Bethesda, MD 20817 (use 20892 for Courier)
Telephone: 301-451-7383
Fax: 301-480-2408
Email: ernstn@niaid.nih.gov

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

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

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

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

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

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

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

The overall Product Development Strategy, made up of the Milestone and Timeline and the Product Development Plan sections, is limited to 12 pages. (Note: Applicants should not add attachments in the Research and Related Other Project Information Component to circumvent page limits.)

Milestones and Timeline

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

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

Product Development Plan

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

• A statement of the intended use/indication of the proposed product and public health gap the product is intended to fill.
• A statement of the value of the project, including lay description of key technology objectives, innovation, and advantages compared to competing products, technologies, or services.
• A clear description of the goal(s) of the project, including one (or more) intermediate products (tools), final product(s) or stage(s) of product development to be completed during the award period. A specific final product profile that is intended for licensing indication is not requested.
• Descriptions of preclinical product development activities pertaining to the product proposed. For the purpose of this FOA, preclinical is defined as all activities beyond diagnostic assay/platform/prototype development.
• The performance specifications the product (diagnostic assay, method, technology, etc.), should have to demonstrate that it is equivalent or superior to the gold standard for identifying the proposed agent(s), including clinical sensitivity in appropriate human samples, clinical specificity in appropriate human samples, analytical sensitivity (limit of detection), analytical reactivity (pathogen strains detected for each pathogen), analytical specificity (cross-reactivity), and analytical reproducibility (test replicates at different agent concentrations, at different sites, etc.). If no FDA-cleared test is available for the agent(s), the specifications should be equivalent to or exceed performance specifications of FDA-cleared tests for similar types of agent(s).
• Data that support the selection of the candidate product for further development, including an assessment of the present capacity of the diagnostic method, technology or assay to meet the performance specifications.
• Discussions with FDA, if any, which are relevant to development activities for the candidate product.

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

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

Biographical Sketch: Citations for patents and patent applications that are relevant to the project and are owned or licensed by the applicant should be included in Selected Peer-reviewed Publication and Patent Citations.

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

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

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

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

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

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

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

• A clear description of the capabilities of the platform, method, technology or assay;
• A clear description of how the diagnostic/technology will be used;
• Plans for determining the sensitivity, specificity and validation of the technology, assay or diagnostic; and
• A description of a normally sterile specimen type (for example, blood, CSF, or pleural fluid) from which organisms will be detected. For applications that include detection of pathogens in HAP/VAP, describe how contamination with colonizing organisms will be addressed.

Applications must include plans to detect one or more of the following Gram-negative bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and extra-intestinal pathogenic Escherichia coli.

Diagnostic platforms/technologies intended for differential diagnosis and/or clinical decision making must incorporate multiple bacterial targets, including at least one of the Gram-negative species listed above and may include diagnosis of additional pathogens. A proposed diagnostic intended solely to facilitate clinical trial enrollment for a pathogen-specific drug may target a single Gram-negative species from the above list and optimally, would report antibacterial susceptibility profiles.

If plans include the detection of the target pathogen(s) in the context of other types of infections, such as HAP/VAP, specify how contamination with colonizing organisms will be addressed.

Industry Participation: All applications submitted by academic organizations must demonstrate substantive investment and participation in the project by at least one industrial participant as outlined in Section I.

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

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide with the following additional instruction. Abstracts of all patents and patent applications that are relevant to the project and are owned or licensed by the applicant should be submitted.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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

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

See more tips for avoiding common errors.

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

Mandatory Meetings

A mandatory 1 day progress review meeting will be held annually at the NIAID, or at a site designated by the NIAID Program Official, during which the Program Director/Principal Investigator and appropriate Key Personnel will present project accomplishments. A critical determinant of success will be the degree of communication between the PD/PI, Project Leaders and other significantly involved parties. Therefore, in addition to the one meeting listed above, additional meetings, which may be necessary for coordination of project activities, may be scheduled, if justified. Regular telephone and written communication with the NIAID Program Official is considered to be very important and is strongly encouraged.

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

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

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

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

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 diagnostic against one or more of the specified agents? Will a proposed diagnostic that includes the capability to report the antimicrobial susceptibility for each agent significantly influence clinical care/actions?

Investigator(s)

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

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?

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?Is the likelihood of successful project completion high given the current state of research and development as well as the proposed technical approach?

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

Are the milestones and timelines adequately described and appropriate for the proposed work? Is the product development strategy appropriate for the proposed work? Is sufficient information provided on the performance specifications of the product to demonstrate it is equivalent or superior to the gold standard for identifying the proposed agent? Is the preclinical product development adequately described for the product? Will the proposed industrial participation enhance the development of the project?

Environment

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

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

Product Development Strategy

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html

TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Dr. Maureen Beanan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-0999
Email: beananm@mail.nih.gov

Dr. Nancy Lewis Ernst
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-7383
Email: ernstn@niaid.nih.gov

Ms. Anneliese Galczynski
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-8328
Email: galczynskia@mail.nih.gov

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

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