N62645-PA-19-2 Program Announcement - _FINAL.docx

PROGRAM ANNOUNCEMENT

I. GENERAL INFORMATION

1. Agency Name

Naval Medical Logistics Command (NMLC)

2. Funding Opportunity Title

Research and Development of Protective Vaccines and Other Countermeasures Against Infectious Disease Agents of Military Importance.

3. Sponsor’s Name

Naval Medical Research Center – Silver Spring

4. Funding Opportunity Number

N62645-PA-19-2

5. Catalog of Federal Domestic Assistance (CFDA) Number

12.340

6. Catalog of Federal Domestic Assistance (CFDA) Title

Naval Medical Research and Development

7. Application Submission Deadline

The application submission deadline is: 10:00 A.M. Eastern Time, 19 September 2019.

8. Funding Decision Date

The Government plans to make a funding decision by: 27 September 2019.

Each applicant will receive notification of the funding decision.

9. Funding Opportunity Description

i. Program Description

Infectious diseases have negatively impacted U.S. military operations dating as far back as the Revolutionary War. Recent outbreaks of Ebola, Chikungunya and Zika combined with the ongoing threats posed by malaria, infectious diarrhea and multi-drug resistant bacteria in regions where U.S. military personnel operate underscore the need for preventive measures to mitigate against the impact that infectious diseases have on the operational forces of the U. S. The goal of this Cooperative Agreement is to engage in a collaborative research and development (R&D) effort for protective vaccines and other countermeasures targeting the causative agents of malaria, travelers’ diarrhea, rickettsial pathogens, multi-drug resistant bacteria, and emerging viral diseases.

This work will focus on pursuing approaches for the development of effective vaccines, diagnostics against these pathogens, and therapies. Diagnosis is crucial in thoroughly evaluating candidate vaccines at clinical trial sites where the target disease is endemic. Other countermeasures may include passive immunotherapy and refined use of commercial off-the-shelf antimicrobial agents. For wound infections with multi-drug resistant bacteria, new treatment modalities that can either stand alone or augment current antimicrobial therapeutics should significantly improve clinical outcomes.

The collaborative countermeasure development efforts will target four areas of research: 1) Development and clinical evaluation of vaccines and other countermeasures against pathogens responsible for diarrheal illness; 2) Development and clinical evaluation of vaccines and novel countermeasures against malaria (Plasmodium falciparum and P. vivax); 3) Development and clinical evaluation of vaccines and other countermeasures against rickettsial and emerging viral pathogens; and 4) Development of non-antibiotic approaches, including the use of bacteriophages, to combat multi-drug resistant bacteria.

ii. Award Description

The intent of this award is to fund an organization that can provide a collaborative research effort and creative intellectual input to develop and evaluate preventive and therapeutic countermeasures for P. falciparum and P. vivax malaria, infectious diarrhea, rickettsial pathogens, emerging and re-emerging viral pathogens including dengue, MERS-CoV, Chikungunya, Zika, novel flu viruses and multi-drug resistant bacteria. The award will be issued as a cooperative agreement between the recipient and the Government (the Infectious Diseases Directorate, Naval Medical Research Center [IDD-NMRC]). The award recipient (awardee) will collaborate with IDD-NMRC to develop and implement scientific research efforts and share substantial programmatic involvement with IDD-NMRC. IDD-NMRC will provide overall program direction and scientific focus through the Grants Officer Representative (GOR). Research activities under this cooperative agreement will take place primarily within IDD-NMRC laboratories to minimize the need for the awardee to purchase specialized equipment or acquire additional laboratory space to conduct the research. This will result in significant savings to the U. S. Government. Collaborative research personnel provided by the awardee must have the necessary security clearances (if required) in place for access to IDD-NMRC facilities and IT networks. The awardee must have the capacity to award sub-grants and subcontracts as needed to meet research and development needs.

iii. Infectious Diseases Research Award Focus Areas

IDD-NMRC has already begun research and development activities toward developing and evaluating vaccines and countermeasures targeting infectious diseases of military importance. Many products that have been developed are at the pre-clinical stages or are in early Phase 1 / Phase 2 human clinical trials. The awardee will collaborate with IDD-NMRC to achieve the below listed goals of the program:

Infectious Diarrhea/Travelers’ Diarrhea

· Develop countermeasures against Campylobacter jejuni (CJ);

· Develop countermeasures against Enterotoxigenic Escherichia coli (ETEC);

· Conduct FDA-regulated clinical trials associated with ETEC, Shigella and Campylobacter countermeasure development and evaluation;

· Conduct epidemiological investigations to better understand the morbidity of travelers’ diarrhea to include acute illness, chronic sequelae, incidence, etiology and pathogen distribution; and

· Support countermeasure research and evaluation for other diarrheal pathogens of military interest.

Viral/Rickettsial Pathogens and Diagnostics

· Develop countermeasures for emerging and re-emerging viral and rickettsial pathogens;

· Develop therapeutics for treating or preventing emerging and re-emerging viral and rickettsial diseases;

· Conduct epidemiological investigations to better understand the incidence, etiology and pathogen of viral and rickettsial disease distribution;

· Develop countermeasures against Orientia tsutsugamushi;

Malaria

· Develop countermeasures against P. falciparum malaria; and

· Develop countermeasures against P. vivax malaria.

Multi-drug Resistant Bacteria

· Develop bacteriophage therapeutics against multi-drug resistant bacteria;

· Develop novel approaches to enhance care of patients suffering from wound infections with multi-drug resistant bacteria to improve clinical outcomes; and

· Conduct epidemiological investigations to better understand the incidence, etiology and pathogen distribution.

Cross-cutting Support

· Develop a humanized mouse model suitable for testing and down-selecting experimental vaccine candidates and studying the pathogenesis of infectious diseases of military importance; and

· Develop and clinically evaluate testing platforms for clinical and discovery research.

iv. General Information

IDD-NMRC is engaged in devising materiel solutions to mitigate the detrimental effects of infectious disease illness on military operations around the globe. To date several products have been developed targeting malaria, ETEC, Campylobacter, dengue and other arboviruses. Most of these products are preventive vaccines that have gone from concept development at the laboratory bench to early Phase 1 and Phase 2 clinical testing in humans. Investigators are also pursuing therapeutic modalities utilizing convalescent plasma, directed passive immunization, humanized immunoglobulin preparations, probiotic approaches, bacteriophage intervention, and small molecule prophylaxis. These studies also provide critical insight to questions regarding immune mechanisms of protection for these diseases.

Awardee efforts are needed to facilitate the clinical evaluation of vaccine candidates and other countermeasures, and include regulatory capabilities in areas such as:

1. Clinical Trials Regulatory Expertise (FDA-regulated research)

2. Epidemiology, Biostatistics

3. Program Management

During the performance period, the awardee will work collaboratively with IDD-NMRC towards advancing current products in its research portfolio to more advanced clinical testing and possible licensure while also assisting in devising new concepts and backup strategies for the current products.

v. Summary of Responsibilities

(a) Countermeasures for Bacterial Diarrhea The awardee will contribute efforts to advance the research and development of bacterial vaccines for ETEC and Campylobacter. The work will be conducted in IDD-NMRC laboratories where awardee personnel will collaborate with NMRC civilian and military personnel. Specific collaborative efforts will include:

· Develop countermeasures against Campylobacter jejuni (CJ)

· Conduct molecular biology studies of CJ in the human intestinal tract;

· Conduct preclinical Campylobacter candidate vaccine and countermeasure development studies; and

· Conduct Campylobacter human clinical trials and provide regulatory and epidemiology expertise and assistance.

· Develop countermeasures against Enterotoxigenic Escherichia coli (ETEC)

· Design, purify and characterize key ETEC antigens for incorporation into a preventive countermeasure product;

· Conduct preclinical ETEC candidate vaccine or other countermeasure development studies; and

· Conduct ETEC human clinical trials and provide regulatory and epidemiology expertise and assistance.

· Conduct human clinical trials for the purpose of Shigella vaccine development

· Conduct human clinical trials evaluating countermeasures other than vaccines against military relevant diarrhea

· Conduct epidemiological studies and reviews to support enteric disease countermeasure development.

(b) Countermeasures for Malaria The awardee will contribute to the collaborative effort in order to advance the research and development of a vaccine or other countermeasure against P. falciparum and P. vivax malaria. The work will be conducted in IDD-NMRC laboratories where awardee personnel will collaborate with NMRC civilian and military personnel. Specific collaborative efforts will include:

· Develop countermeasures against P. falciparum malaria.

· Conduct preclinical P. falciparum candidate vaccine or other countermeasure development studies. These studies may require the use of other species of malaria more conducive for study in animal models of malaria infection.

· Determine biomarkers and immune mechanisms of protection induced by candidate vaccines in animal models and humans.

· Conduct clinical trials.

· Develop countermeasures against P. vivax malaria.

· Conduct preclinical P. vivax candidate vaccine or other countermeasure development studies. These studies may require the use of other species of malaria more conducive for study in pre-clinical animal models of malaria infection.

· Determine biomarkers and immune mechanisms of protection induced by candidate vaccines in animal models and humans.

· Conduct clinical trials.

(c) Vaccines and Therapeutics for Emerging and Re-emerging Viral Diseases The awardee will pursue a collaborative effort to advance the research and development of a vaccine that is protective against all four serotypes of dengue virus. Work should also include therapeutic and preventive modalities targeting Zika, Chikungunya, MERS-CoV and novel influenza viruses. The work will be conducted in IDD-NMRC laboratories where awardee personnel will collaborate with NMRC civilian and military personnel. Specific efforts will include:

· Develop countermeasures against emerging and re-emerging viral pathogens

· Identify/discover novel methods and/or antigens/targets suitable for vaccines for emerging viral diseases.

· Conduct clinical trials and provide epidemiology expertise and assistance.

· Develop therapeutics for treating or preventing emerging and re-emerging viral diseases

· Identify/discover novel methods and/or antigens/targets suitable for therapeutics of emerging viral diseases.

· Conduct research and development to enhance the immunogenicity of dengue DNA vaccines.

· Conduct clinical trials and provide epidemiology expertise and assistance.

· Explore the use of the humanized mouse model to down select experimental vaccine candidates and study the pathogenesis of infectious diseases of military importance.

(d) Countermeasures for rickettsial diseases The awardee will pursue a collaborative effort to advance the research and development of a vaccine that is protective against rickettsial pathogens. The work will be conducted in IDD-NMRC laboratories where awardee personnel will work closely with NMRC civilian and military personnel. Specific collaborative efforts will include:

· Develop vaccines or other countermeasures against Orientia tsutsugamushi and Coxiella burnetii.

· Discover and characterize novel antigens that could be used in a future vaccine.

· Conduct preclinical candidate vaccine or other countermeasure development studies.

· Conduct epidemiological studies to direct further clinical development efforts.

(e) Development of the Humanized Mouse Model

· Explore the use of the humanized mouse model to down select experimental vaccine candidates and study the pathogenesis of infectious diseases of military importance.

· Research therapeutic monoclonal and polyclonal antibody products to treat and/or prevent infectious diseases of military importance.

(f) Development of Countermeasures Against Multidrug Resistant Wound Infections

· Advance the use of bacteriophage therapy to treat infections complicated by multidrug resistant bacteria, focusing primarily on Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens.

· Research the use of biomarkers that may be predictive of clinical outcomes in skin and soft tissue infections.

· Research the use of novel therapeutic approaches to treat and manage bacterial wound infections.

vi. Oversight of Research Activities Under the Cooperative Agreement:

The NMRC GOR will provide oversight of research activities covered under the cooperative agreement. The GOR will coordinate with program managers (PMs) from each IDD-NMRC department. The PMs will coordinate with project investigators to stay abreast of progress toward meeting established milestones.

vii. Use of Human Subjects / Human Biological Substances and Animal Species

Research activities utilizing human subjects and biological substances are a core requirement of this agreement. All Federal and Department of Defense (DoD) regulations must be met as applicable. Applicable laws and directives are rigorous and detailed. Regulatory support activities required under this agreement include: (1) FDA filings in support of Investigational New Drug (IND) and similar applications; (2) compliance with Sponsor requirements; (3) preparation and submission of protocols, reports and supporting materials in support of new and ongoing Institutional Review Board (IRB) reviews and DoD-mandated scientific reviews (SRB-reviews); and (4) as needed, some DoD-funded research involving human subjects requiring HRPO review in accordance with DoD Federal Acquisition Regulation Supplement (DFARS) Protection of Human Subjects in Research directives. A minimum of 3-months and additional submission requirements will be needed for studies requiring HRPO review.

Research activities utilizing animal species is a core requirement of this agreement. All Federal and Department of Defense (DoD) regulations must be met as applicable. Please note that no assurances are required for intramural research that involves animals; however, if the intramural research includes certain animal species (dog, cat, non-human primate, and marine mammals), the protocol must be approved by the Bureau of Medicine and Surgery Veterinary Affairs Department prior to the initiation of work.

10. Point(s) of Contact Questions of a technical or business nature should be submitted in writing to the NMLC Grants Officer via email at jayme.l.fletcher2.civ@mail.mil and jaclyn.p.svincek.civ@mail.mil. Please cite the funding opportunity number in the subject line.

The deadline for the submission of questions is 10:00 AM Eastern Time on 03 September 2019.

Amendments or revisions to the funding opportunity will be posted to the following web page: Grants.gov (http://www.grants.gov/)

11. Funds Available and Anticipated Number of Awards

NMLC intends to award a single Cooperative Agreement for a 60-month period of performance (divided into five 12-month budgets) to the awardee for collaborative efforts with IDD-NMRC on infectious diseases research. Funding will be provided on the base award (and added incrementally) to provide for the personnel and research materiel that is necessary for the collaborative research being conducted under the cooperative agreement. All direct and indirect costs of any sub-award (sub-grant or sub-contract) must be included in the total direct costs of the primary award.

The maximum allowable funding for the entire 60-month period is $56,826,775.52M, inclusive of direct and indirect costs. Funding is planned as follows:

Period

Amount

Within the guidelines provided in the Application Instructions, funds can cover:

· Salary to include administrative support

· Research supplies

· Equipment and equipment maintenance

· Clinical research costs, including research subject compensation

· Animal research costs

· Support for developing and maintaining collaborations

· Assistance and collaboration with writing and submitting manuscripts and reports

· Travel between collaborating institutions

· Travel costs to attend scientific/technical meetings

· Other direct costs as described in the Application Instructions for the budget

II. ELIGILIBLITY INFORMATION

1. Eligibility

All Qualified sources from academia and industry may submit applications under this funding opportunity. Historically Black Colleges and Universities (HBCUs) and Minority Institutions (MIs) are encouraged to submit applications and join others in submitting applications. However, no portion of this funding opportunity will be set aside for HBCU and MI participation.

Federally Funded Research & Development Centers (FFRDCs), including Department of Energy National Laboratories, are not eligible to receive an award under this funding opportunity. Cost sharing/matching is not an eligibility requirement.

2. Dun and Bradstreet Data Universal Numbering System (DUNS) Number and System for Award Management (SAM)

Applicant organizations and all sub-recipient organizations must have a DUNS number to submit applications to Grants.gov. The applicant organization must also be registered in the Entity Management functional area of the SAM with an “Active” status to submit applications through the Grants.gov portal. Applicant organizations should verify the status of their Entity registration in SAM well in advance of the application submission deadline. Allow several weeks to complete the entire SAM registration process. If an applicant has not fully complied with the requirements at the time the Federal awarding agency is ready to make a Federal award, the Federal awarding agency may determine that the applicant is not qualified to receive a Federal award and use that determination as a basis for making a Federal award to another applicant. Refer to the General Application Instructions for further information regarding Grants.gov requirements.

The Federal Funding Accountability and Transparency Act of 2006 (Public Law 109-282), as amended by Section 6202 of Public Law 110-252, requires that all agencies establish requirements for recipients reporting information on sub-awards and executive total compensation as codified in the award provision in Appendix A to 2 CFR part 170, “Reporting subaward and executive compensation information (refer to REP Article IV. Reporting on subawards and executive compensation (September 2017)) in the DoD R&D General Terms and Conditions dated July 2018. Any company, non-profit agency or university that applies for financial assistance as either a prime or sub-recipient under this funding opportunity must provide information in its application that describes the necessary processes and systems in place to comply with the reporting requirements identified in 2 CFR 200.330.

III. APPLICATION AND SUBMISSION INFORMATION

Please refer to the separate Application Instructions document.

IV. EVALUATION INFORMATION

1. Review and Selection Process

The award decision will be based on a competitive selection of the application resulting from a three-tier review process.

The first tier is a completeness review that ensures that the application provides support of all research focus areas outlined in Section I.9.iii of this Program Announcement. Failure of an application to document support of all research focus areas may (at the discretion of the Grants Officer) cause an application to not be forwarded for the peer and programmatic reviews and therefore not be eligible to be funded.

The second tier is a peer review of applications against established criteria for determining technical merit as identified below in paragraph 2.

The third tier is a programmatic review that compares applications to each other and makes a recommendation for funding to the Commander (NMRC) for concurrence, and then to the NMLC Grants Officer for award processing.

2. Review Criteria

A. Peer Review

To determine technical merit, all applications will be evaluated according to the criteria listed below. Criteria 1 through 3 are of equal importance, and when combined, are more important than Criteria 4.

1) Overall scientific and technical merits of the application;

2) Military relevance and contributions of the proposed effort;

3) The applicant’s capabilities, related organizational experience, previous work, facilities, techniques, key personnel (qualifications, capabilities and experience) or unique combinations of these which are integral factors for achieving the proposed objectives; and

4) Budget: Whether the budget is appropriate for the proposed effort and within the funding limitation of this funding opportunity.

B. Programmatic Review

The following equally weighted criteria will be used by programmatic reviewers to make the funding recommendation.

1) Ratings and evaluations of the peer reviewers;

2) Programmatic relevance;

3) Adherence to the intent of the funding opportunity; and

4) Evaluation on the cost of the applicant’s solution(s) based on the work to be performed in accordance with the scope of this project and organizational experience.

V. AWARD ADMINISTRATION INFORMATION

1. Administrative Requirements

Organizations must register in Grants.gov to submit applications through the Grants.gov portal. The registration process may take several weeks, so organizations should register as soon as possible.

All applicants must:

· Be registered as an Entity within the SAM (http://www.sam.gov) and receive confirmation of an “Active” status before submitting an application through Grants.gov;

· Maintain an active SAM registration with current information at all times during which it has an active Federal award or an application under consideration by any agency;

· Provide its DUNS number in each application it submits to the agency;

· Have the management capability and adequate financial and technical resources, given those that would be made available through the cooperative agreement, to execute the program of activities envisioned under the cooperative agreement;

· Have a satisfactory record of executing such awards (if a prior recipient of an award); and Be otherwise qualified and eligible to receive a cooperative agreement under applicable laws and qualifications.

Prior to making an assistance agreement award where the Federal share is expected to exceed the simplified acquisition threshold, as defined in 2 CFR 200.88, over the period of performance, the Federal awarding agency is required to review and consider any information about the applicant that is available in the Federal Awardee Performance and Integrity Information System (FAPIIS).

An applicant organization may review FAPIIS and submit comments to FAPIIS on any information about the organization that a Federal awarding agency previously entered and is currently available in FAPIIS.

The Federal awarding agency will consider any comments by the applicant, in addition to other information in the designated integrity and performance system, in making a judgment about the applicant’s integrity, business ethics, and record of performance under Federal awards when determining a recipient’s qualification prior to award, according to the qualification standards of the Department of Defense Grant and Agreement Regulations (DoDGARs), Section 22.415.

2. Certifications

A. Representations for Assistance Agreements

The applicant that is selected for award will be required to complete NMLC’s Representations Form during the negotiations process. This form will be sent to the applicant who is selected for award by the NMLC Grants Officer.

B. Certification Regarding Lobbying Activities

Cooperative Agreement awards greater than $100,000, under Section 1352, Title 31, U.S.C. (PL 101-121, Section 319), require a certification of compliance with a national policy mandate concerning lobbying. Grant and Cooperative Agreement applicants shall provide this certification by electronic submission of SF424 (R&R) as a part of the electronic application submitted via Grants.gov (complete Block 17). The certification applies to each applicant seeking federal assistance funds exceeding $100,000.

CERTIFICATION REGARDING LOBBYING ACTIVITIES

Certification of compliance with the national policy requirement regarding lobbying activities is required from all recipients of awards over $100,000. Submission of this certification is required by 31 USC 1352 and is a prerequisite for making or entering into an award over $100,000. Complete SFLLL (Disclosure of Lobbying Activities), if applicable, and attach to Block 18 of the SF424 (Research & Related) (Application for Federal Assistance) Form.

Certification for Contracts, Grants, Loans, and Cooperative Agreements By signing an application, the applicant certifies, to the best of his or her knowledge and belief, that:

(1) No Federally appropriated funds have been paid or will be paid, by or on behalf of the undersigned, to any person for influencing or attempting to influence an officer or employee of an agency, a member of Congress, an officer or employee of Congress, or an employee of a member of Congress in connection with the awarding of any Federal contract, the making of any Federal grant, and the making of any Federal loan, the entering into of any cooperative agreement, and the extension, continuation, renewal, amendment, or modification of any Federal contract, grant, loan, or cooperative agreement.

(2) If any funds other than Federal appropriated funds have been paid, or will be paid, to any person for influencing or attempting to influence an officer or employee of any agency, a member of Congress, an officer or employee of Congress, or an employee of a member of Congress in connection with this Federal contract, grant, loan, or cooperative agreement, the undersigned shall complete and submit SFLLL (Disclosure of Lobbying Activities), in accordance with its instructions.

(3) The undersigned shall require that the language of this certification be included in the award documents for all subawards at all tiers (including subgrants, and contracts under grants, loans, and cooperative agreements) and that all subrecipients shall certify and disclose accordingly.

This certification is a material representation of fact upon which reliance was placed when this transaction was made or entered into. Submission of this certification is a prerequisite for making or entering into this transaction imposed by 1352 USC 31. Any person who fails to file the required certification shall be subject to a civil penalty of not less than $10,000 and not more than $100,000 for each such failure..

3. Funding

Funding may be provided incrementally during the life of the award. Under cost-reimbursement type awards, payments are made in response to monthly vouchers or invoices submitted by the awardee. Under grants and cooperative agreements, advance payments are normally made periodically, in accordance with the negotiated payment schedule included in the award document.

4. Government Obligation

Only a warranted Grants Officer may obligate the Government to the expenditure of funds for an award under this funding opportunity. The Government does not fund preparation of applications or support research that is inferred from discussions with technical program officers.

5. Maximum Obligation

NMLC does not modify awards to provide additional funds for such purposes as reimbursement for unrecovered indirect/facilities and administrative costs resulting from the establishment of final negotiated rates or for increases in salaries, fringe benefits, and other costs.

VI. OTHER INFORMATION

1. Government Property/Government Furnished Equipment (GFE) and Facilities

Government research facilities, laboratory equipment and IT equipment (desktop computers, laptop computers, and mobile devices) are available and should be considered as potential Government-furnished equipment/facilities. The use of these facilities, equipment and IT devices are authorized, provided the personnel requiring the use of this equipment have the necessary training and security clearances in place.

2. Security Classification

To facilitate intra-program collaboration and technology transfer, the Government will attempt to enable technology developers to work at the unclassified level to the maximum extent possible. If access to classified material will be required at any point during performance, the applicant must clearly identify such need in the Technical Volume.

Note: Normally, work under an assistance agreement does not require access to classified material.

3. Use of Human Subjects in Research

A. Applicable Regulations

Human Subjects: The performance of research involving human subjects shall be conducted in accordance with The Common Federal Policy for the Protection of Human Subjects codified by the Department of Health and Human Services at 45 CFR 46 Part A, and implemented by the Department of Defense with 32 CFR 219 “The Common Rule,” 10 USC 980 “Limitation on Use of Humans as Experimental Subjects,” Department of Defense (DoD) Instruction 3216.02 “Protection of Human Subjects and Adherence to Ethical Standards in DoD-Supported Research,” and Secretary of the Navy Instruction 3900.39D (series) “Human Research Protection Program,” as well as other applicable federal and state law and regulations, and Department of the Navy guidance. The recipient must be cognizant of and abide by the additional restrictions and limitations imposed on the DoD regarding research involving human subjects, specifically as they regard vulnerable populations, recruitment of military research subjects, informed consent and surrogate consent, and chemical and biological agent research. Food and Drug Administration regulation and policies may also apply. Department of the Navy, Human Research Protection Program (DON HRPP) guidance for human subject research is located at https://www.med.navy.mil/Pages/InfoViewPage.aspx?ItemID=6

Any human subject research to be conducted under this cooperative agreement requires a Human Research Protection Officer (HRPO) approval. No funds are to be expended until the HRPO review has been received by the NMLC Grants Officer and a subsequent modification has been issued to the assistance agreement to list the approved human subject research protocol by name.

Example from the terms and conditions of a NMLC assistance agreement award:

“Human subject research is not allowed under this award, except under the protocol(s) named below:

A. Protocol A.

B. Protocol B.”

When a HRPO review has been received by the NMLC Grants Officer, the research protocol will be added to this list in the award terms and conditions, thereby lifting the restriction on human subject research under the named protocols only.

B. Required Assurances

The objectives of the Research and Development of Protective Vaccines and Other Countermeasures Against Infectious Disease Agents of Military Importance award dictate that there will be Human Subject Research conducted by the successful awardee. Therefore, the awardee must possess the following assurances:

· An active (i.e., not expired) Federal-wide Assurance (FWA) appropriate for research to be conducted under the award. The FWA shall remain active for the duration of the award. The FWA is issued by the Department of Health and Human Services.

C. Intramural Research

Intramural research is research (or services supporting the research) conducted by one or more Government agencies using Government facilities with Government staff (to include Principal Investigators) and under Government protocols and a Government IRB.

The awardee must complete the following requirements prior to the performance of research involving human subjects or expenditure of funding on such effort (whichever occurs first):

· The awardee shall rely on the Government organization’s designated IRB as the IRB of record for the research to be supported under the award. The awardee shall enter into a DoD Institutional Agreement for IRB Review (IAIR) with the designated Government organization. The IAIR will apply to all human subject research supported under the specific study(s). The IAIR shall be executed by the parties no later than 30 days after the effective date of the award, or before commencement of performance of research involving human subjects or expenditure of funding, whichever occurs first.

· Awardee personnel providing support under the award shall complete initial and ongoing research ethics and human subject protections training appropriate to each individual’s level of involvement, duties, and responsibilities. Specific training requirements will be directed by the designated Government organization.

· The awardee shall obtain written notice from the designated Government organization that: (i) awardee and/or partner personnel identified as supporting human subject research under the award have been added to the applicable research protocol; (ii) performance of the protocol has been approved by the designated Government organization’s Institutional Official and that performance may begin; (iii) a determination that the protocol meets exemption criteria including the exemption category or classification of research risk (e.g., minimal risk); (iv) confirmation of continuing acceptability of the awardee and/or partner’s assurances; and (v) Human Research Protection Official (HRPO) review of the protocol has been completed. Awardee personnel shall not commence performance of research involving human subjects until stated notice is received.

· The awardee shall notify the designated Government organization of personnel changes under the award. New personnel that will perform research involving human subjects will be required to complete applicable training and will be added to the applicable research protocol(s) as discussed above.

The awardee shall supplement administrative efforts by the designated Government organization to ensure compliance with the listed requirements for intramural research. This includes identifying contract personnel that contribute to the required human subject research under the award and maintaining records of training and other documentation to demonstrate compliance with human research protection requirements under the award. The awardee shall also assist with the continuing review of the human subject research that is necessary under the award.

Failure of the awardee to comply with the listed requirements for intramural research will result in the issuance of a stop-work order to immediately suspend, in whole or in part, work and further payment under this award or will result in other issuance of suspension of work and further payment for as long as determined necessary at the discretion of the Grants Officer.

The listed requirements for intramural research are applicable to and shall be included in all subawards made by the awardee’s administrator to organizations that may conduct human subject research.

D. Extramural Research Extramural research is research that is funded by the Government, but that is conducted using awardee or subawardee facilities with awardee or subawardee staff (to include Principal Investigators) and under the awardee or subawardee’s protocols and IRB.

If the awardee or subawardee is conducting extramural research involving human subjects must complete the following requirements prior to the performance of research involving human subjects or expenditure of funding on such effort (whichever occurs first):

The awardee or subawardee must submit the following documents (if applicable) for review by the designated Government organization’s HRPO:

· IRB Approval Letter or IRB Exemption Determination Letter

· IRB Risk level Determination for Non Exempt Research (Minimal or Greater than Minimal Risk)

· IRB Approved Protocol for Non Exempt Research

· IRB Approved Informed Consent Form for Non Exempt Research (or documented exemption in protocol)

The awardee or subawardee must receive written notice that the research has been reviewed by the designated Government organization’s HRPO and that performance may begin.

Failure of the awardee or subawardee to comply with the listed requirements for extramural research will result in the issuance of a stop-work order to immediately suspend, in whole or in part, work and further payment under this award or will result in other issuance of suspension of work and further payment for as long as determined necessary at the discretion of the Grants Officer.

The listed requirements for extramural research are applicable to and shall be included in all sub-awards made by the awardee administrator to organizations that may conduct human subject research.

4. Use of Animal Species in Research

A. Applicable Regulations

The performance of research involving animal species shall be conducted in accordance with rules on animal acquisition, transport, care, handling, and use in (i) 9 CFR Parts 1-4, Department of Agriculture rules that implement the Laboratory Animal Welfare Act of 1966 (7 U.S.C. 2131-2159, as amended); and (ii) the “Guide for the Care and Use of Laboratory Animals,” National Institutes of Health Publication No. 86-23; Prohibitions on the purchase or use of dogs and cats for certain medical training purposes, in Section 8019 (10 U.S.C. 2241 note) of the DoD Appropriations Act, 1991 (Pub. Law 101-511) and Rules of the Departments of Interior (50 CFR Parts 10-24) and Commerce (50 CFR Parts 217-227) implementing laws and conventions on the taking possession, transport, purchase, sale, export or import of wildlife and plants, including the Endangered Species Act of 1973 (16 U.S.C. 1531-1543); Marine Mammal Protection Act (16 U.S.C. 1361-1384); Lacey Act (18 U.S.C. 42); DoD Instruction (DoDI) 3216.01, “Use of Animals in DoD Programs and the Convention on International Trade in Endangered Species of Wild Fauna and Flora.

All other applicable federal and state law and regulations, DoD and Department of the Navy guidance also applies.

B. Intramural Research

Intramural research is research (or services supporting the research) conducted by one or more Government agencies using Government facilities with Government staff (to include Principal Investigators) and under Government protocols and a Government IRB.

Please note that no assurances are required for intramural research that involves animals; however, if the intramural research includes certain animal species (dog, cat, non-human primate, and marine mammals), the protocol must be approved by the Bureau of Medicine and Surgery Veterinary Affairs Department, prior to the initiation of work.

Failure of the awardee to comply with the listed requirements for intramural research will result in the issuance of a stop-work order to immediately suspend, in whole or in part, work and further payment under this award or will result in other issuance of suspension of work and further payment for as long as determined necessary at the discretion of the Grants Officer.

The listed requirements for intramural research are applicable to and shall be included in all subawards made by the awardee’s administrator to organizations that may conduct research involving animal species.

D. Extramural Research

Extramural research is research that is funded by the Government, but that is conducted using awardee or subcontracted partner facilities with awardee staff (to include Principal Investigator (PI)) and under the awardee’s protocols and IRB.

The awardee’s organization or associated partners conducting extramural research involving animal species must comply with the following requirements prior to the performance of research involving animal species or expenditure of funding on such effort (whichever occurs first):

For extramural research involving certain animal species (dog, cat, non-human primate, and marine mammals), a site visit to the facility may be required at the discretion of the Bureau of Medicine and Surgery Veterinary Affairs Department.

Failure of the awardee to comply with the listed requirements for extramural research will result in the issuance of a stop-work order to immediately suspend, in whole or in part, work and further payment under this award or will result in other issuance of suspension of work and further payment for as long as determined necessary at the discretion of the NMLC Grants Officer.

The listed requirements for extramural research are applicable to and shall be included in all subawards made by the awardee to organizations that may research involving animals.

5. Biosafety and Biosecurity Requirements.

The awardee and all subawardees must comply with applicable provisions of DOD 6055.18-M, Safety Standards for Microbiological and Biomedical Laboratories, including ensuring compliance with standards meeting at least the minimum applicable requirements of the current edition of Centers for Disease Control and Prevention, “Biosafety in Microbiological and Biomedical Laboratories (BMBL),” and National Institutes of Health, “The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).” The NIH Guidelines are available at https://osp.od.nih.gov/biotechnology/biosafety-and-recombinant-dna-activities/.

6. Research Involving Recombinant or Synthetic Nucleic Acid Molecules.

Applications which call for experiments using Recombinant or Synthetic Nucleic Acid Molecules and/or organisms and viruses containing Recombinant or Synthetic Nucleic Acid Molecules must include documentation of compliance with the National Institutes of Health "Guidelines for Research Involving Recombinant DNA Molecules". The NIH Guidelines are available at https://osp.od.nih.gov/biotechnology/biosafety-and-recombinant-dna-activities/.

Performance of experiments using Recombinant or Synthetic Nucleic Acid Molecules and/or organisms and viruses containing Recombinant or Synthetic Nucleic Acid Molecules, shall not begin until the awardee receives notice from the NMLC Grants Officer that NMLC has reviewed and accepted the awardee’s documentation.

In order for NMLC to accomplish that review, the awardee shall provide the following documentation as part of the applicant’s Attachment 1 - Technical Volume.

The awardee will not receive a separate approval for the proposed research under this paragraph. If the applicant received the award based on a proposal including the two aforementioned items, the awardee can assume the NMLC Grants Officer has accepted that documentation. If such research is added later, the awardee will have to provide the two items of documentation listed above and a revised proposal. If this research is approved, the awardee will receive a modification incorporating the revised proposal.

For research involving countries outside the United States, if the host country has established rules for the conduct of recombinant or synthetic nucleic acid molecule research, then the research must be in compliance with those rules. If the host country does not have such rules, the proposed research must be reviewed and approved by an NIH-approved IBC or equivalent review body and accepted in writing by an appropriate national governmental authority of the host country. The safety practices that are employed abroad must be reasonably consistent with the NIH Guidelines.

7. Organizational Conflicts of Interest

All Applicants and proposed sub-awardees must affirm whether they are providing Systems Engineering and Technical Assistance (SETA) or similar assistance to any NMRC technical office(s) through an active contract or subcontract. All affirmations must state which office(s) the applicant assists and identify the corresponding, prime assistance agreement/contract numbers. Affirmations shall be furnished at the time of application submission. All facts relevant to the existence or potential existence of organizational conflicts of interest (2 CFR 200.112 and 2 CFR 200.318(c)) must be disclosed. The disclosure shall include a description of the action the applicant has taken or proposes to take to avoid, neutralize, or mitigate such conflict. Applications that fail to fully disclose potential conflicts of interests or do not have acceptable plans to mitigate identified conflicts will be rejected without technical evaluation and withdrawn from further consideration for award. If a prospective applicant believes that any conflict of interest exists or may exist (whether organizational or otherwise), the applicant should promptly raise the issue with NMLC by sending his/her contact information and a summary of the potential conflict by e-mail to the Business Point of Contact in Section I, item 10 above, before time and effort are expended in preparing an application and mitigation plan. If, in the sole opinion of the Grants Officer after full consideration of the circumstances, any conflict situation cannot be effectively avoided or mitigated, the application may be rejected without evaluation and withdrawn from further consideration for award under this funding opportunity.

8. Project Meetings and Reviews

Project meetings and reviews will be conducted at the departmental level as well as in conjunction with scheduled reviews and meetings as required by the funding sponsors. For costing purposes, applicants should assume that most of these meetings will be at or near NMRC or other awardee or Government facilities. Interim meetings are likely, but these will be accomplished via video telephone conferences, telephone conferences, or via web-based collaboration tools.

9. Award Negotiations

Extramural research programs are implemented predominantly through the award of assistance agreements that are made to an organization, not to the individual Principal Investigator(s) (PI[s]). A representative from NMLC will contact the business official authorized to negotiate on behalf of the PI’s organization. The award start date will be determined during the negotiation process.

Only an appointed NMLC Grants Officer may obligate the Government to the expenditure of funds. No commitment on the part of the Government should be inferred from discussions with any other individual. Any pre-award costs associated with a research effort are made at an organization’s own risk. The incurring of pre-award costs by an organization does not impose any obligation on the Government in the absence of appropriations, if an award is not made, or if an award is made for a lesser amount than an organization expected.

10. Reporting Requirements for Awards

The Government requires periodic reports to be submitted to continue the research and funding through the entire period of performance. Specific reports required by the Government will be described in the award and may include: quarterly, mid-term, annual, and final research progress reports; fiscal reports; non-exempt human studies reports; and animal use reports.

11. Equipment

Unless otherwise specified in the award, the title to equipment or other tangible property purchased with Government funds will vest in institutions of higher education or with non-profit organizations whose primary…