N62645-PA-17-1 Program Announcement.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-17-1

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: 1:00 P.M. Local Time, July 21, 2017

6. Funding Decision Date

The government plans to make a funding decision by: August 10, 2017

Each applicant will receive notification of the funding decision.

7. Funding Opportunity Description

A. Program Description Infectious diseases have negatively impacted U.S. military operations dating as far back as the Revolutionary War. Recent conflicts and outbreaks involving infectious agents such as Ebola, Chikungunya and Zika underscore the need for preventive measures to mitigate the effects on operational forces of the U. S. The goal of this Cooperative Agreement is to engage in a collaborative research and development (R&D) effort to devise protective vaccines and other countermeasures targeting the causative agents of malaria, travelers’ diarrhea, rickettsial pathogens and emerging viral diseases. Research will also focus on developing novel countermeasures targeting multi-drug resistant bacteria that are associated with combat related wound infections.

This work utilizes novel approaches for antigen discovery essential for the development of effective vaccines and diagnostics against these pathogens. Diagnosis is crucial in thoroughly evaluating candidate vaccines at vaccine test sites where the target disease is endemic. Other countermeasures include passive immunotherapy and refined use of commercial on-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 patient clinical outcomes.

To accomplish these goals, the collaborative vaccine and countermeasure development efforts will involve four areas of research: 1) Development and clinical evaluation of vaccines and other countermeasures against bacterial pathogens responsible for diarrheal illness, 2) Development and clinical evaluation of vaccines 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) Advancing the use of bacteriophage in treating multi-drug resistant bacteria.

B. Award Description

The intent of this award is to fund an organization that can provide collaborative assistance with manpower (scientists, research associates, research assistants, laboratory aides , nurses, clinical trials staff, program managers, and technicians), materiel (research supplies, equipment), and clinical trials (research subject compensation) for research efforts focusing on the development and evaluation of preventive and therapeutic countermeasures for P. falciparum and P. vivax malaria, bacterial causes of infectious diarrhea, rickettsial pathogens, 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 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. Collaborative research personnel provided by the awardee must have the necessary work permits/visas and security clearances 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.

i. 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 vaccines against Campylobacter jejuni (CJ).

· Develop vaccines against Enterotoxigenic Escherichia coli (ETEC).

· Collaborate with NMRC to conduct and provide regulatory assistance for research studies and clinical trials associated with ETEC, Shigella and Campylobacter countermeasure development and evaluation.

· Provide epidemiology expertise and collaborate with NMRC in order to better understand the morbidity of travelers’ diarrhea to include acute illness, chronic sequelae, incidence, etiology and pathogen distribution.

Viral/Rickettsial Pathogens and Diagnostics

· Develop vaccines for emerging and re-emerging viral pathogens.

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

· Develop vaccines against Orientia tsutsugamushi.

Malaria

· Develop vaccines against P. falciparum malaria.

· Develop vaccines 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.

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.

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

ii. General Information

IDD-NMRC has for years been 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 2 clinical testing in humans. Investigators are also pursing therapeutic modalities utilizing convalescent plasma as well as humanized immunoglobulin preparations derived from transchromosomic cows and goats, which have been utilized to answer research questions regarding immune mechanisms of protection. These products are being evaluated as passive immunization candidates for clinical use.

Collaborative efforts are needed to facilitate the clinical evaluation of vaccine candidates, other countermeasures and research and administrative initiatives (which provide technical, basic science and epidemiologic assistance). These include personnel and regulatory capabilities in areas such as:

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

2. Epidemiology, Biostatistics

3. Program Management The humanized mouse model, currently under development, has been instrumental in the evaluation of vaccines against malaria, dengue, HIV and rickettsial pathogens. It has also shown promise in the study of disease pathogenesis, and the generation of therapeutic monoclonal and polyclonal products.

IDD-NMRC investigators, in collaboration with scientists from other NMRC directorates, have successfully completed pre-clinical research that demonstrated the utility of bacteriophage therapy in treating wound infections with antibiotic resistant Acinetobacter baumanii.

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.

iii. Summary of Responsibilities

(a) Vaccines for Bacterial Diarrhea The awardee will contribute to the collaborative effort (both in manpower and materiel assistance) in order 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 vaccines against Campylobacter jejuni (CJ)

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

· Conduct preclinical Campylobacter candidate vaccine development studies

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

· Develop vaccines against Enterotoxigenic Escherichia coli (ETEC)

· Design, purify and characterize key ETEC antigens for incorporation into a vaccine product.

· Conduct preclinical ETEC candidate vaccine development studies

· 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

· Provide regulatory and epidemiology guidance and expertise.

(b) Vaccines for Malaria The awardee will contribute to the collaborative effort (both in manpower and materiel assistance) in order to advance the research and development of a vaccine 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 vaccines against P. falciparum malaria.

· Conduct preclinical P. falciparum candidate vaccine 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 vaccines against P. vivax malaria.

· Conduct preclinical P. vivax candidate vaccine 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 contribute to the collaborative effort (both in manpower and materiel assistance) in order to advance the research and development of a vaccine that is protective against all four serotypes of dengue virus. Work will also be performed to devise 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 collaborative efforts will include:

· Develop vaccines 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) Vaccines for rickettsial diseases The awardee will contribute to the collaborative effort (both in manpower and materiel assistance) in order 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 against Orientia tsutsugamushi.

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

· Conduct preclinical candidate vaccine development studies.

· Provide epidemiology expertise and assistance.

(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.

· Generate 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 mostly on Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens.

· Identify biomarkers predictive of clinical outcomes in skin and soft tissue infections.

· Explore other novel therapeutic approaches to treat and manage bacterial wound infections.

iv. 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.

v. 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), (4) as needed, some DoD-funded research involving human subjects will also require 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.

8. Point(s) of Contact

Questions of a technical or business nature should be submitted in writing to the NMLC Grants Officer via email at usn.detrick.navmedlogcomftdmd.mbx.research@mail.mil. Please cite the funding opportunity number in the subject line.

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

9. Funds Available and Anticipated Number of Awards

NMLC intends to award a single Cooperative Agreement for a single 18 month period 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 18 month base period is $27.7M, inclusive of direct and indirect costs. Funding is planned as follows:

Amount

Total

$27.7M

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

Collaboration and assistance with the development/writing/submission of grant proposals

· 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

All responsible 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.

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 2 CFR 33.110. 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 33.220. An entity is exempt from this requirement UNLESS in the preceding fiscal year it received: a) 80 percent or more of its annual gross revenue in Federal contracts (and subcontracts), loans, grants (and subgrants), and cooperative agreements; b) $25 million or more in annual gross revenue from Federal contracts (and subcontracts), loans, grants (and subgrants), and cooperative agreements; and c) the public does not have access to information about the compensation of the senior executives through periodic reports filed under section 13(a) or 15(d) of the Securities Exchange Act of 1934 or section 6104 of the Internal Revenue Code of 1986.

III. APPLICATION AND SUBMISSION INFORMATION

See 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 two-tier review process. The first tier is a peer review of applications against established criteria for determining technical merit. The second tier is a programmatic review that compares applications to each other and makes a recommendation for funding to the Commanding Officer (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 more important than Criteria 4. Criteria 1 through 3 are of equal importance.

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;

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

4) Evaluation on the cost of their 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.

System for Award Management (SAM): All applicants must:

· Be registered as an Entity with 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.

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 Contract Specialist.

B. Certification Regarding Lobbying Activities Cooperative Agreement awards greater than $100,000, under Section 845, 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 following certification applies to each applicant seeking federal assistance funds exceeding $100,000:

CERTIFICATION REGARDING LOBBYING ACTIVITIES

(1) No Federal appropriated funds have been paid or will be paid by or on behalf of the applicant, 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, 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 the Federal contract, grant, loan, or cooperative agreement, the applicant shall complete and submit Standard Form-LLL, “Disclosure Form to Report Lobbying,” in accordance with its instructions.

(3) The applicant shall require that the language of this certification be included in the award documents for all sub-awards at all tiers (including subcontracts, sub-grants, and contracts under grants, loans, and cooperative agreements) and that all sub-recipients 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 Section 1352, title 31, U.S.C. 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

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 3900.39 (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, and 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 http://www.med.navy.mil/bumed/humanresearch/.

B. Required Assurances

The objectives of the IDD-NMRC award dictate that there will be intramural Human Subject Research conducted by the various departments within IDD-NMRC. It is anticipated that clinical trials will take place at either the NMRC Clinical Trials Center or the WRAIR clinical trials center, although it is possible that other non-DoD clinical trials centers may be utilized. Regardless, the awardee and any partner organizations conducting Human Subject Research 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 Principle Investigators) and under Government protocols and a Government IRB.

The awardee or associated partners conducting intramural 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 and associated partner(s) shall rely on the Government organization’s designated IRB as the IRB of record for the research to be supported under the award. The consortium partner shall enter into a DoD Institutional Agreement for Institutional Review Board (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 and/or partner 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 contract and/or partner personnel shall not commence performance of research involving human subjects until stated notice is received.

· The awardee contract and/or partner 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 subcontracted partner facilities with awardee staff (to include Principle Investigators) and under the awardee’s protocols and IRB.

The awardee’s organization or associated partners 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 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 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 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 subawards made by the awardee to organizations that may conduct human subject research.

3. 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 Department of Defense 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); and Convention on International Trade in Endangered Species of Wild Fauna and Flora.

All other applicable federal and state law and regulations, Department of Defense 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 Principle 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 Principle Investigators) 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):

· A copy of the animal use protocol signed and submitted by the principle investigator to the supporting institute.

· A copy of an approval letter from the IACUC (Institutional Animal Care and Use Committee) that is supporting the animal use.

· A completed copy of the BUMED Animal Use Appendix for Research Involving Animals.

· Copies of the last two USDA Inspection reports from the supporting Institute.

· Confirmation of institutes OLAW Assurance (if applicable).

· Confirmation of institutes AAALAC Accreditation (if applicable).

· If neither (5 ) or (6 )applies then: A statement signed by the Institutional Official that states the care and use of animals will be conducted in accordance with the National Research Council's Guide for the Care and Use of Laboratory Animals and applicable Federal and DoD Regulations.

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 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 conduct human subject research.

4. Research Involving Recombinant DNA Molecules

Applications which call for experiments using recombinant DNA molecules and/or organisms and viruses containing recombinant DNA molecules must include documentation of compliance with the National Institutes of Health "Guidelines for Research Involving Recombinant DNA Molecules", of July 5, 1994 (59 FR 34496) and amended April 27, 2016.

5. Organizational Conflicts of Interest

All Applicants and proposed sub-awardees must affirm whether they are providing scientific, 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 (FAR 9.5) 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. In accordance with FAR 9.505 and without prior approval, an organization cannot simultaneously be a SETA and a research and development performer. 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 7 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.

6. Project Meetings and Reviews

Project meetings and reviews will be conducted at the IDD-NMRC 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.

7. 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.

8. 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.

09. 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 purpose is conducting scientific research. Normally, the title will vest in the recipient if vesting will facilitate scientific research performed by the organization for the Government. Title to equipment or other tangible property purchased by for-profit organizations will conditionally vest in the organization subject to the requirements of 2 Code of Federal Regulations (CFR) part 200. However, if the award is subsequently transferred to a new organization, the Department of Defense (DoD) reserves the right to require the transfer of equipment purchased with the award funds to the Federal Government or to an eligible third party.

10. Inquiry Review

If an application is not recommended for funding, the organization or PI may submit an inquiry within 30 business days after the date on which the funding status notification email for that application is sent. The inquiry must specifically address a factual or procedural error that is believed to have occurred during review of the application. Inquiries in response to funding decisions should be submitted to the NMLC Grants Officer via email at usn.detrick.navmedlogcomftdmd.mbx.research@mail.mil. Please cite the funding opportunity number in the subject line.

An inquiry review panel will determine whether a factual or procedural error occurred in either peer or programmatic review and, if so, recommend corrective action where appropriate. Considering the recommendation of the inquiry review panel, a final determination will be made by the NMLC Grants Officer and is not subject to appeal. Questions related to the inquiry review process prior to or after submitting an inquiry should be directed to the NMLC Grants Officer via email at usn.detrick.navmedlogcomftdmd.mbx.research@mail.mil. Please cite the funding opportunity number in the subject line.

11. J-1 Visa Waiver

Each organization is responsible for ensuring that the personnel associated with any application recommended for funding are able to complete the work without intercession by the DoD for a J-1 Visa Waiver on behalf of a foreign national in the United States under a J-1 Visa.

12. Clinical Trial Registry

PIs are required to register clinical trials individually on www.clinicaltrials.gov using a Secondary Protocol ID number designation of “NMLC-NMLC Award Number” (e.g., NMLC-N62645-17-2-XXXX). If several protocols exist under the same application, the Secondary Protocol ID number must be designated “NMLC-NMLC Award Number-A, B, C, etc.” (e.g., NMLC-N62645-17-2-XXXX-A). Clinical trials must be registered prior to enrollment of the first patient. All trials that meet the definition on the National Institutes of Health database (see http://prsinfo.clinicaltrials.gov/, click on “Data Element Definitions”) are required to register. Failure to do so may result in a civil monetary penalty and/or the withholding or recovery of grant funds as per U.S. Public Law 110-85.

13. Title to Inventions and Patents

The recipient has patent rights in Subject Inventions, as defined in 37 CFR 401.2, in accordance with (IAW) 37 Code of Federal Regulations (CFR) part 401, subject to the requirements of 37 CFR 401.14. The Federal government shall have a nonexclusive, nontransferable, irrevocable, paid-up license to practice or have practiced for or on behalf of the United States any Subject Invention. Furthermore, the Federal Government, IAW 37 CFR part 401 has the right to reproduce, publish or otherwise use the data first produced under an award and to authorize others to receive, reproduce, publish or otherwise use such data for Federal purposes. Data will be delivered to the Federal Government IAW the agreement, but not less than annually. The recipient may copyright any work subject to copyright protection. The DoD reserves a royalty-free, nonexclusive and irrevocable right to reproduce, publish, or otherwise use the work for Federal purposes and to authorize others to do so.

14. Administrative and National Policy

This award is governed by the guidance in 2 Code of Federal Regulations (CFR) part 200, "Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards," as modified and supplemented by the Department of Defense's (DoD) interim implementation found at 2 CFR part 1103, "Interim Grants and Cooperative Agreements Implementation of Guidance in 2 CFR part 200" (79 FR 76047, December 19, 2014), all of which are incorporated herein by reference and the articles below.

Provisions of Chapter I, Subchapter C of Title 32, CFR, "DoD Grant and Agreement Regulations," other than parts 21, 22, 32, 33 and 37, continue to be in effect and are incorporated herein by reference, with applicability as stated in those provision

15. NMLC Assistance Agreement Terms & Conditions

The following terms and conditions (T&Cs) apply to assistance agreement awards made by NMLC:

T&Cs for Institutions of Higher Education, Hospitals, and Other Non-Profit Organizations T&Cs for For-Profit Organizations T&Cs for Foreign Institutions

These T&Cs are located at http://www.med.navy.mil/sites/nmlc/Pages/DBU-RnG.aspx.

17 | N62645-PA-17-1 Program Announcement