N62645-PA-19-1 Program Announcement.DOCX

PROGRAM ANNOUNCEMENT

I. GENERAL INFORMATION

1. Agency Name

Naval Medical Logistics Command (NMLC)

2. Funding Opportunity Title

Austere Environment Consortium for Enhanced Sepsis Outcomes (ACESO) Award (Cooperative Agreement).

3. Sponsor’s Name

Naval Medical Research Center - Frederick

4. Funding Opportunity Number

N62645-PA-19-1

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: 10:00 A.M. Eastern Time, 05 August 2019.

8. Funding Decision Date

The government plans to make a funding decision by: 15 August 2019.

Each applicant will receive notification of the funding decision.

9. Funding Opportunity Description

i. ACESO Program Description

The Department of the Navy, Bureau of Medicine and Surgery (BUMED) is interested in receiving applications to continue a very successful Naval Medical Research Center (NMRC) program dedicated to improving the prevention, early recognition, diagnosis, and effective treatment of severe sepsis from all causes in austere environments. This program will continue to be supported by an established consortium of investigators with skills and expertise in infectious disease, critical care, systems biology, global health, and other relevant fields who will work together on a coordinated program of research. This consortium, named the Austere Environments Consortium for Enhanced Sepsis Outcomes (ACESO), will continue to generate knowledge and research data that can be rapidly translated into preventing and improving the outcome of severe sepsis in austere or resource-limited settings.

Etiologic causes of human disease that currently have no targeted therapies, and those that pose unique risks to the military with respect to emerging outbreaks, susceptibility of deployed forces, and/or deliberate release scenarios will continue to be the primary focus. ACESO’s research platform addresses gaps in the Department of Defense's (DoD) capabilities for improving knowledge on pathogens that manifest in symptoms of severe sepsis in austere settings, whether they be endemic, emerging, or biological threats. ACESO leverages a network of expert investigators, trained study staff, and established in-country infrastructure to execute research evaluating clinical management strategies and the pathogenesis of severe sepsis, to characterize the clinical aspects of sepsis related to various potential biological threats, to improve outcomes for severe sepsis in austere environments, to investigate the immunopathogenesis and long-term sequelae of infectious etiologies (especially hemorrhagic fevers), and to augment the capability to gather important clinical data in outbreak settings of severe emerging disease.

ii. Award Description

The NMRC sepsis research program (and thus ACESO) is intended to reduce the threat of severe sepsis and its causative agents to DoD forces deployed in resource-limited settings. Understanding the pathogenesis and immunology of severe sepsis syndrome (SSS), and developing appropriate clinical management to reduce mortality from SSS-causing diseases will directly enhance the mission of the DoD biodefense/emerging infectious disease enterprise to protect service members and the nation from biological threats. This information would also have implications within the fields of civilian public health and global health and security, as the economic and social impact of severe sepsis in developing countries is significant. The intent of this award is to fund an organization that can continue serving as the integrating coordinator for ACESO and work closely with NMRC to develop and implement scientific efforts of the consortium. The award is designed to maintain a hub that can bring together the expertise of military research laboratories with relevant accomplished civilian scientists (i.e., from the fields of infectious disease, critical care, computational biology, systems biology, and global health) at outstanding organizations and with appropriate patient populations in resource-limited and resource-replete settings.

The ACESO award resulting from this program announcement will be issued as a cooperative agreement between the recipient (ACESO Coordinator) and the Government (the Naval Medical Logistics Command [NMLC]). The ACESO Coordinator will share substantial programmatic involvement with NMRC. NMRC will provide program direction and scientific focus through the Grants Officer's Representative (GOR).

The ACESO Coordinator designated through this award will support ACESO-related research activities of consortium partners through ACESO award funds, with the potential exception of military treatment facilities (MTF's) or other US military or US Government institutes. The ACESO Coordinator will provide management and support (e.g., research personnel, supplies) to the federal research partners through various and appropriate means; however, no direct funds will be provided to any government institution by the ACESO Coordinator. Long term, ACESO will conduct studies and activities that support the award focus areas.

iii. ACESO Award Research Focus Areas

SSS is a clinical syndrome caused by numerous and diverse pathogens and typically presents as an undifferentiated febrile illness. SSS continues to profoundly impact military and civilian populations, being a foremost cause of in-hospital mortality. The effect of SSS would very likely be amplified in settings of large outbreaks of emerging or pandemic disease, biological warfare, or bioterrorism where resources could quickly be overwhelmed. Finally, while the epidemiology of SSS in under-developed countries is poorly characterized, it appears to be a significant cause of mortality. In austere or resource limited settings (e.g., deployed personnel, public health emergencies, poorly developed countries), initial presentation of sepsis may occur where access to advanced diagnostics and intensive care unit (ICU)-level care is limited. Improving outcomes in these settings depends on disease prevention, recognizing SSS early before resulting in shock, effective therapeutic interventions for non-agent specific SSS, rapid presumptive diagnosis of specific etiologic cause, and tailored therapies for known microbial cause.

In addressing these gaps, ACESO established a platform of world-class clinical research in resource-limited settings with complementary clinical research sites for SSS in United States (US) MTFs. This platform continues to implement research protocols around the world to address NMRC’s goals. Under the clinical protocols, ACESO will continue to collect physiological, biochemical, and microbiological data for integration into a comprehensive systems approach to investigate common pathogenic pathways of SSS. Recognizing the continued need for advanced analytics, ACESO will continue reaching out to established experts in bioinformatics and data analysis to support our comprehensive research approach.

Goal 1: Develop and continuously improve clinical management algorithms that improve morbidity and mortality of SSS that can be employed in austere or resource-limited settings.

Objective 1.1: Establish a platform with the capability for randomized clinical trials (RCTs) in resource-limited settings across multiple selected and/or established locations.

Objective 1.2: Evaluate clinical management algorithms for severe sepsis.

Goal 2: Identify unique physiological and biochemical markers for sepsis, severe sepsis, and agent identification based on host-pathway responses.

Objective 2.1: Establish a platform with the capability for high-quality clinical research in resource-limited settings.

Objective 2.2: Implement cutting-edge research protocols to identify host markers indicative of prognosis and diagnosis of sepsis and severe sepsis.

Goal 3: Discover common pathways of pathogenesis in severe sepsis that can be exploited for clinical intervention.

Objective 3.1: Acquire clinical and laboratory data.

Objective 3.2: Develop a database architecture for integration of large complex datasets.

Objective 3.3: Integrate and analyze data.

Goal 4: Identify signatures for host-based pathogen identification and targets for rapid bedside diagnostics. Partner with developers to test candidate diagnostics in clinical settings.

Objective 4.1: Evaluate candidate diagnostics at ACESO research sites.

Objective 4.2: Host-based signatures identified under Goal 2 as diagnostic for a particular pathogen or pathogen class will be rigorously evaluated.

Goal 5: Explore targets for novel host-directed therapeutics.

Goal 6: Validate novel applications of existing or emerging technologies for performance improvement in the clinical care of SSS in austere or resource-limited settings.

Objective 6.1: Transition the RCT for evaluation of bedside ultrasound.

Goal 7: Explore the immunology and long-term sequelae of bacterial and viral threat agents associated with SSS.

Objective 7.1: Evaluate the immunology and long-term sequelae of Ebola Virus (EBOV) infection.

Objective 7.2: Evaluate the immunology and long-term sequelae of patients with severe sepsis.

Goal 8: Integrate with larger efforts, develop, and implement improved sepsis care and bio-surveillance systems for emerging diseases and biological threats in strategically important developing countries.

Objective 8.1: Coordinate with the Defense Threat Reduction Agency (DTRA) Cooperative Biologic Engagement Program (CBEP).

Objective 8.2: Establish professional collaborations as necessary.

Goal 9: Establish outbreak response capabilities in order to improve understanding and clinical-management of high-consequence infections occurring in outbreaks/epidemics in resource-limited settings.

Objective 9.1: Establish working partnership with The World Health Organization (WHO) and other international players, and establish expertise in the clinical care field and research in outbreak response and sepsis in austere environments.

Objective 9.2: Collect on-the-ground observations and outbreak data to identify appropriate targets for further ACESO research efforts.

Objective 9.3: Write research protocols to address critical scientific questions in the appropriate recognition and care of sepsis during outbreaks.

iv. Consortium Oversight

An Executive Committee (EC) will consist of ACESO Partner Institution Principal Investigators and select appointed individuals, and will make recommendations regarding operational, tactical, and daily operational issues to the GOR. The EC is expected to maintain monthly or more frequent contact with a government appointed GOR, who will maintain full documentation of interactions. The ACESO Coordinator and the EC will propose sepsis-specific clinical research studies in resource-limited settings. The EC will not only supervise the conduct of clinical studies and determine which Consortium organizations will participate in each study, but will also make decisions regarding ongoing research, new projects, and annual budgets (with the consent of the GOR).

The Scientific Steering Committee (SSC) will be comprised of between 5 and 10 outside experts who will be appointed by NMRC and NMLC, and are not directly affiliated with ACESO research. The SSC will review progress and provide advice and guidance on scientific relevance, military relevance, and the coordination of proposed projects.

The SSC will review proposed Consortium studies and provide approval and recommendations prior to implementation. The SSC will also recommend areas of future study to the Consortium. The SSC will meet in person or virtually at least annually for 1-day meetings, during which current and future research will be presented concurrently with strategic direction from ACESO leadership. Based on these reports and presentations, the SSC and NMRC/NMLC staff will evaluate progress, provide feedback, and recommend modifications as needed to facilitate the success of the Consortium.

The GOR will be responsible for distilling the recommendations of both the SSC and the EC and presenting recommendations to the NMLC Grants Officer. The NMLC Grants Officer will issue the final approval of any proposed projects and/or studies.

v. Summary of Responsibilities

ACESO Management: ACESO leadership will be responsible for two main areas of program management and support: (1) Overall ACESO Program Management, and (2) ACESO Research Program Management.

1. Overall ACESO Program Management:

Overall ACESO Program Management (including headquarters management) responsibilities of the ACESO Coordinator, in coordination with the Biodefense Research Directorate (BDRD) ACESO Director (Government employee), will include (but are not limited to):

A. ACESO Coordinator will serve as the Deputy Director of the Consortium, and the primary liaison with the GOR.

B. Developing collaborations with Government, academic, and private organizations to achieve ACESO goals. This includes oversight of international clinical research network sites in Cambodia, Liberia, Uganda, and Ghana, as well as future research sites and oversight of any required domestic and international sub-awards, subcontracts, consultant agreements, and vendor agreements.

C. Providing administrative, contracting/purchasing services (for equipment and supplies required for the execution of consortium goals), human resources management, travel services, graphics production services and logistics expertise to support ACESO.

D. Providing information technologies (IT) support including but not limited to: the management of a Consortium-developed comprehensive data collection and data management systems that address the needs of all Clinical Study Sites in terms of access to data, data security, and data integrity measures.

E. Providing financial support including but not limited to: the management of costs to support the Clinical Study Sites (including provision of personnel, equipment, and materials required to conduct approved clinical studies).

F. Providing public relations support including but not limited to: management of Consortium-developed procedures for the timely publication of major findings and other public dissemination of data.

G. Ensuring that the Consortium adheres to the planned timeline and milestones for overall study execution.

H. Managing Consortium-designed and approved procedures for external scientific review, prioritization, and implementation of clinical studies proposed by or through Consortium members.

I. Establishing and managing procedures to ensure that all sites maintain compliance with local Institutional Review Boards (IRBs) and the Department of the Navy Human Research Protection Program (DON HRPP) for the proper conduct of clinical studies and the protection of human subjects.

J. Ensuring the standardized analyses of specimens, imaging products, and other data.

K. Managing Consortium-developed quality assurance and quality control mechanisms for study monitoring, including but not limited to:

1. Onsite monitoring program, to include safety conditions and issues.

2. Management plan for the handling, distribution, and banking of specimens and imaging products generated from Consortium studies.

3. Registration, tracking, and reporting of participant accrual.

4. Timely medical review, rapid reporting, communication of adverse events, and data management/coordination among all sites.

5. Interim evaluation and consideration of measures of outcome.

6. Implement statistical execution plans/support for all Consortium clinical studies.

L. Managing Consortium-developed intellectual and material property issues among organizations participating in the Consortium, should these issues arise.

M. Attending a pre-award planning meeting (hosted by NMLC) to discuss any technical or performance issues with the proposed Consortium and to support the award negotiations process (if required).

N. Developing, organizing, and submitting periodic written progress reports, annual reports, and a final written comprehensive report to NMRC and NMLC.

O. Providing safety and occupational health support.

P. Providing quality management program development and support.

Q. Providing facilities and facilities management support.

R. Providing clinical research project management.

S. Providing regulatory and clinical operation support.

T. Providing statistical / resource / data management and analysis support.

Unless otherwise specified, ACESO HQ will be co-located with NMRC BDRD at the Fort Detrick, MD facility. NMRC does not expect all requisite expertise and capacity for HQ management to be supplied as an integral part of the ACESO HQ; (if properly outlined and detailed) a significant portion of this capability could rely on reach-back to a parent organization.

As part of attaining the goals and performing the effort set forth above, studies may be conducted under this award that are funded separately from, and in addition to, projects funded by the Government. These separately non-Government funded studies must be identified by study titles and approved by and coordinated with the GOR and the NMLC Grants Officer.

2. Overall ACESO Research Program Management:

The ultimate goal of ACESO is to develop improved clinical management for sepsis in resource- limited settings. This will be accomplished through basic and applied research related to human clinical trials of sepsis, and improved research and application of clinical management in the care of severe emerging disease outbreaks.

ACESO Research Program Management responsibilities of the ACESO Coordinator (in coordination with and final approval of the GOR) will include (but are not limited to):

A. Responsibility for overall program implementation.

B. Overseeing a network of ACESO sites in Cambodia, Ghana, Liberia, and Uganda as well as opening and overseeing future research sites as the program expands.

C. Designing and overseeing clinical research studies to answer key research questions.

D. Developing the data analysis strategy for the consortium and conducting/managing advanced statistical analysis of research data.

E. Writing, publishing and presenting research findings in high-impact peer reviewed journals and conferences (subject to Government Approval).

F. Identifying and evaluating promising scientific pursuits, research tools, and collaborations.

G. Providing international laboratory program support.

H. Providing support by enhancing professional degree and leadership opportunities for partners at international sites and in turn building and expanding the consortium’s ability to develop human resource capacity that allows the consortium to optimize, capitalize and manage local research opportunities.

I. Providing support by recruiting and training host-country physicians to staff clinical research projects and Subject Matter Experts (SME)’s in infectious disease and critical care to serve in a supervisory or consultative role and in turn expanding the consortium’s capabilities to conduct clinical research in management of severe infections.

J. Providing multidisciplinary communication support by developing internal and external liaisons that can foster communication.

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

Research activities utilizing human subjects, biological substances and animal species are a core requirement of this agreement. For the requirements to conduct these types of research, please refer to the following section of this program announcement: VI.3. Use of Human Subjects in Research, VI.4. Use of Animal Species in Research, VI.5. Biosafety and Biosecurity Requirements and VI.6.Research Involving Recombinant or Synthetic Nucleic Acid Molecules.

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 thomas.l.hood26.civ@mail 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 22 July 2019.

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

11. Funds Available and Anticipated Number of Awards

NMLC intends to award a single Cooperative Agreement for a single 60 month period to the selected ACESO Coordinator to support the ACESO Consortium. The ACESO Coordinator will provide funding support for the selected clinical study sites and Consortium partners as sub-awards. Funding will be provided on the base award (and added incrementally) to provide for the operation of the consortium. 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 budget periods are included at the application stage to aid in cost proposal evaluation. The award will contain a single 60 month Contract Line Item Number (CLIN).

The maximum allowable funding for the entire 60 month base period is $52.10M, inclusive of direct and indirect costs. Funding is planned as follows:

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. Verify the status of the applicant organization’s 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 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. 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

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 three research focus areas. Failure of an application to document support of all three 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 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.

· 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).

· 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, accessible through SAM, 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 Contract Specialist.

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

Section 1352, Title 31, U.S.C. (PL 101-121, Section 319) entitled “Limitation on use of appropriated funds to influence certain Federal contracting and financial transactions.”

(1) No Federally appropriated funds have been paid or will be paid by or on behalf of the under-signed, 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 Federally 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 undersigned shall complete and submit Standard Form-LLL, “Disclosure Form to Report Lobbying,” in accordance with its instructions.

(3) The undersigned shall require that the language of this certification be included in the award documents for all sub-awards at all tiers (including subcontracts, 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 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

Human Subjects: The performance of research involving human subjects shall be conducted IAW 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, 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/.

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 and thereby lifting the restriction on human subject research under the named protocols only.

B. Required Assurances

The objectives of the ACESO award dictate that there will be Human Subject Research conducted by the consortium partner organizations. Therefore the ACESO Coordinator 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.

Consortium 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 consortium partner 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 consortium partner 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 consortium facilities with consortium staff (to include Principle Investigators) and under the consortium’s protocols and IRB.

Consortium 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 consortium partner 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 consortium partner 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 consortium partner 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 consortium 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 IAW 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 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 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):

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.

You 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 you receive notice from the NMLC Grants Officer that NMLC has reviewed and accepted your documentation.

In order for NMLC to accomplish that review, you shall provide following documentation as part of your Attachment 1 - Technical Volume.

You will not receive a separate approval for your proposed research under this paragraph. If you received the award based on a proposal including the two aforementioned items, you can assume the NMLC Grants Officer has accepted that documentation.