Attachment_-_HHS-NIH-NIAID-BAA2017-1_-_Amendment_1.pdf

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2017 Omnibus Broad Agency Announcement No. HHS-NIH-NIAID-BAA2017-1 – Amendment 1

Solicitation Issue Date: March 3, 2017

Participating NIAID Divisions:

1. Division of Allergy, Immunology, and Transplantation (DAIT)

2. Division of Microbiology & Infectious Diseases (DMID)

Issuing Office: Office of Acquisitions, DEA, NIAID, NIH, 5601 Fishers Lane, Room 3D32, MSC 9821, Bethesda, MD 20892-9821

Issuing Contracting Officer: George Kennedy kennedyg@mail.nih.gov

(240) 669-5170

This solicitation contains opportunities to submit a proposal under the following distinct Research Areas, which are identified below:

* Proposals must be received by 3:00 PM Eastern Time on the date specified herein. Please see the Proposal Submission Instructions for more information.

RESEARCH

AREA

NIAID

DIVISION

TITLE PAGE

NO.

PROPOSALS

DUE:

001 DAIT Adjuvant Development Program 5 06/13/2017 *

002 DAIT Development of Radiation/Nuclear Medical Countermeasures 16 05/30/2017 *

003 DAIT Development of Radiation/Nuclear Predictive Biomarkers and Biodosimetric Devices

19 05/30/2017 *

004 DMID

Development of Broad Spectrum Therapeutic Products for Biodefense, Anti-Microbial Resistant Infections and Emerging Infectious Diseases

07/03/2017 *

005 DMID Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases

31 07/03/2017 * mailto:kennedyg@mail.nih.gov

NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES (NIAID)

2017 Omnibus Broad Agency Announcement

No. HHS-NIH-NIAID-BAA2017-1

TABLE OF CONTENTS

I. Broad Agency Announcement Information………………………………………………………………. p. 3

II. Contracting Officer Points of Contact…………………………………………………………………….. p. 3

III. Research Areas and Technical Objectives………………………………………………………………… p. 4

1. Division of Allergy, Immunology, and Transplantation (DAIT), Adjuvant Development

Program………………………………………………………..…………………………………….. p. 4

A. Background……………………………………..………………………………………….. p. 4

B. Research Areas

i. Research Area 001: Adjuvant Development Program……………………………………… p. 5

C. Additional Technical Proposal Instructions…………………………..…………………… p. 7

D. Reporting Requirements and Deliverables………………………………………………. p.13

2. Division of Allergy, Immunology, and Transplantation (DAIT), Radiation/Nuclear Countermeasures Program………………………………………………………..…………………………………….. p.14

A. Background……………………………………………………………………………….. p.14

i. Research Area 002: Development of Radiation/Nuclear Medical Countermeasures…… p.16

ii. Research Area 003: Development of Radiation/Nuclear Predictive Biomarkers and

Biodosimetric Devices…………………………………………………………………………… p.19

C. Additional Technical Proposal Instructions………………………………………..…… p.22

D. Reporting Requirements and Deliverables……………………………………………. p.25

3. Division of Microbiology and Infectious Diseases (DMID)………………………………………. p. 27

A. Background……………………………………………………………………………….. p.27

i. Research Area 004: Development of Broad Spectrum Therapeutic Products for Bio-defense, Anti-Microbial Resistant Infections and Emerging Infectious Diseases………. p.27

ii. Research Area 005: Advanced Development of Vaccine Candidates for Biodefense and Emerging Infectious Diseases…………………………………………………………….. p.30

C. Additional Technical Proposal Instructions – DMID…………………………………….. p.33

D. Reporting Requirements and Deliverables – DMID……………………………………… p.39

IV. Instructions, Conditions, and Notices to Offerors………………………………………………………… p.44

1. General Information…………………………………………………………………………. p.44

2. Instructions to Offerors……………………………………………………………………… p.46

A. General Information………………………………………………………………… p.46

B. Technical Proposal Instructions ……………………………………………………. p.50

C. Business Proposal Instructions ………………………………………………………p.76

V. Evaluation Factors for Award …………………………………………………………………….. p.90

VI. Attachments……………………………………………………………………………………………… p.97

I. BROAD AGENCY ANNOUNCEMENT INFORMATION

You are invited to submit a proposal in accordance with the requirements of this BROAD AGENCY ANNOUNCEMENT (BAA). The BAA is governed by Federal Acquisition Regulation (FAR) 6.102 and FAR 35.016, as well as the NIH Policy Manual, Manual Chapter 6035, Broad Agency Announcements. A BAA may be used as a solicitation mechanism for basic and applied research directed toward advancing the state-of-the-art or increasing knowledge or understanding and that part of development not related to the development of a specific system or hardware procurement. BAAs are general in nature, identifying areas of research interest, and shall only be used when meaningful proposals with varying technical/scientific approaches can be reasonably anticipated.

This solicitation contains multiple distinct Research Areas. Offerors may submit a proposal in response to one, any combination of, or all of the Research Areas contained herein. Offers submitted in response to this BAA must present separate detailed technical and business proposals designed to meet the Technical Objectives described for each Research Area proposed. The Statement of Work (SOW), including the specific technical requirements and performance specifications, shall be developed and proposed by the Offeror, not the Government.

Proposals are NOT evaluated against each other since they are not submitted in accordance with a common Statement of Work issued by the Government. Instead, Research and Technical Objectives are provided in the BAA that describe individual Research Areas in which the Government is interested. Proposals received in response to the BAA are evaluated in accordance with the Evaluation Factors for Award specified in this announcement. The Government reserves the right to conduct discussions with all, some, one, or none of the proposals received in response to this BAA. If discussions are conducted, NIAID reserves the right to suggest modifying, adding or deleting milestones, decision points, research plans, processes, schedules, budget or product. The Government also reserves the right to make awards without discussions.

Additionally, the Government reserves the right to accept proposals in their entirety or to select only portions of proposals for award. Multiple awards are anticipated. The selection for award under this BAA will be based upon the evaluation factors, importance to the agency programs, and the availability of funds.

II. CONTRACTING OFFICER POINTS OF CONTACT

This BAA contains Research Areas issued by multiple Divisions within the National Institute of Allergy and Infectious Diseases. The Contracting Officer points of contact for questions related to specific Research Areas issued by the Division of Allergy, Immunology, and Transplantation (DAIT) and Division of Microbiology and Infectious Diseases (DMID) are identified below:

Division of Allergy, Immunology, and Transplantation (DAIT)

Research Area 001: Adjuvant Development Program

Tom Bahrami, M.B.A.

Contracting Officer Phone: (240) 669-5147 E-mail: bahramit@niaid.nih.gov

Research Area 002: Development of Radiation/Nuclear Medical Countermeasures;

Research Area 003: Development of Radiation/Nuclear Predictive Biomarkers and

Biodosimetric Devices

Liem Nguyen mailto:bahramit@niaid.nih.gov

Phone: (240) 669-5144 E-mail: Liem.Nguyen@nih.gov

Division of Microbiology and Infectious Diseases (DMID)

Research Area 004: Development of Broad Spectrum Therapeutic Products for Biodefense, Anti-microbial Resistant Infections and Emerging Infectious Diseases;

Research Area 005: Advanced Development of Vaccine Candidates for Biodefense and

Emerging Infectious Diseases

George Kennedy, J.D.

Phone: (240) 669-5170 Email: kennedyg@mail.nih.gov

III. RESEARCH AREAS AND TECHNICAL OBJECTIVES

1. DIVISION OF ALLERGY, IMMUNOLOGY, AND TRANSPLANTATION (DAIT), ADJUVANT

DEVELOPMENT PROGRAM

A. BACKGROUND:

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and other agencies in the Department of Health and Human Services (DHHS) support extramural research to develop new products to protect the public from the health consequences of infectious pathogens, including emerging infectious diseases, defined as pathogens that have newly appeared in a population or have existed but are rapidly increasing in incidence or geographic range.

As part of this mission, NIAID supports the development of new vaccine adjuvants that stimulate immune responses to: protect against pathogenic infection; specifically activate the appropriate arms of the immune system; and result in stronger, more protective vaccines against emerging infectious diseases.

In 2010, NIAID convened a Blue Ribbon Panel to develop an NIAID Strategic Plan for Research on Vaccine Adjuvants (http://www.niaid.nih.gov/sites/default/files/NIAID- StrategicPlanVaccineAdjuvants.pdf) to guide its adjuvant discovery, development and translational research programs. The NIAID Division of Allergy, Immunology and Transplantation (DAIT), has an interest in supporting the development of adjuvants through this Broad Agency Announcement (BAA), which solicits proposals for a renewed research program that includes the preclinical testing and development of new adjuvant candidates to advance novel adjuvant:vaccines towards licensure for human use. These novel adjuvants will stimulate innate and/or adaptive immune responses. For the purpose of this BAA, adjuvants are defined according to the U.S. Food and Drug Administration (FDA) as “agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen.”

Currently, only three adjuvants have been approved for use in the United States – (1) alum (several aluminum salts), (2) 4’-monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide, adsorbed to alum (AS04), and (3) MF59, an oil-in-water emulsion of squalene oil. Additional research is needed to address limitations of current vaccines including the search for new vaccine adjuvants, which (a) effectively and safely induce selective immune mechanisms associated with protection against specific diseases; (b) can be delivered by different vaccination routes; (c) can mailto:Liem.Nguyen@nih.gov mailto:kennedyg@mail.nih.gov http://www.niaid.nih.gov/sites/default/files/NIAID-StrategicPlanVaccineAdjuvants.pdf http://www.niaid.nih.gov/sites/default/files/NIAID-StrategicPlanVaccineAdjuvants.pdf safely and effectively be used in special populations; (d) enhance currently used vaccines; and (e) mediate long-term immunological memory.

DAIT supports three adjuvant programs: 1) Adjuvant Discovery Program which began in 2003 and was renewed in 2009 and 2014 (BAA-NIAID-DAIT-NIH-AI-2013168); 2) Molecular Mechanisms of Combination Adjuvants began in 2016 (RFA-AI-15-005) and 3) the Adjuvant Development Program, which began in 2008, was renewed in 2013 (BAA-NIAID-DAIT-NIHAI2012146) and currently supports four awards:

HHSN272201300029C Leidos, Frederick, MD HHSN272201300028C NanoBio Corporation, Ann Arbor, MI HHSN272201300022C Tulane University, New Orleans, LA HHSN272201300023C University of Washington, Seattle, WA

These awards are due to expire in September 2018.

The purpose of this solicitation is to renew the Adjuvant Development Program to advance novel adjuvants towards licensure for human use. This initiative supports the development of adjuvants through immunological characterization studies and compound optimization, up to and including IND-enabling studies, for a period not to exceed 5 (five) years. The main emphasis will remain on testing and further development of adjuvants for human licensure as components of licensed or investigational vaccines to protect against one or more non-HIV disease pathogens relevant to human disease. This solicitation supports the development of adjuvants for: 1) novel vaccines against diseases for which no licensed vaccines are currently available; 2) more effective vaccines to replace or supplement those with suboptimal efficacy (e.g., Bacille Calmette-Guerin vaccine for tuberculosis), lack of long-term efficacy (e.g., acellular pertussis vaccine), limited efficacy in special populations or “non-responders” (e.g., vaccines against Hepatitis B); or 3) adjuvants that lessen the need for multiple boosting as is currently the norm for many pediatric vaccines. NIAID is particularly interested in the development of early childhood vaccines with adjuvants other than Alum that would favor a Th1 immune response. In the past, the Adjuvant Development Program has supported the development of adjuvant:HIV immunogen combinations. In this iteration, the offeror shall not propose studies involving HIV. The government may add adjuvant:HIV immunogen-combinations to the research supported under this solicitation, subject to Contractor interest.

The goal of Research Area 001, below, is to support the development of one adjuvant per award by conduct of one or more of the activities illustrated in the research area description below.

B. RESEARCH AREA (DAIT: ADJUVANT DEVELOPMENT PROGRAM)

Research Area 001 – Adjuvant Development Program .

Budget and Award Information

The NIAID estimates that the average annual total cost (direct and indirect costs combined) is approximately $2.0M per award. It is anticipated that the total cost for the award(s) may vary depending upon the scope of the project and the technical objectives of the award(s). Total proposed costs and the length of time for which funding is requested should be consistent with the nature and complexity of the proposed research. The period of performance proposed by an offeror should not exceed five (5) years. The NIAID plans to award up to five (5) contracts.

Awards are anticipated to be made in or around September 2018.

Technical Objectives

The objective of this solicitation is to support the development of one adjuvant:vaccine combination (one adjuvant for one or more licensed or investigational vaccines) toward licensure for human use within the five-year contract period of performance through carrying out one or more of the following activities as specified in the negotiated Statement of Work. For the purpose of this solicitation, an adjuvant is defined as a single immunostimulatory compound or a combination of synergistic stimulatory compounds. For this Research Area an offeror may propose to carry out work that by its nature is not innovative but is essential to move a field forward.

Offerors may submit more than one proposal. Each proposal must address the study of one adjuvant:vaccine combination (one adjuvant for one or more vaccines) against one or more non-HIV disease pathogens relevant to human disease. The development of either preventative or therapeutic adjuvant:vaccines against one or more non-HIV disease pathogen relevant to human disease is acceptable. Each individual proposal shall include development or further optimization of only one adjuvant. For the primary contract, adjuvants shall focus on currently licensed or investigational vaccines to protect against one or more non-HIV disease pathogens relevant to human disease.

Depending on the developmental stage at which an adjuvant is entered into the Program, the offeror may choose to perform some or all of the IND-enabling studies. The Contractor shall be responsible for:

• Optimization of only one adjuvant (for one or more vaccines) for enhanced safety and efficacy; this may include structural alterations or modifications to formulation or delivery.

• Establishment of an immunological profile of activity and immunotoxicity that will be of use to evaluate the capability of the adjuvant to advance to human testing.

• Conduct of Preclinical IND-enabling studies such as pilot lot or cGMP manufacturing of adjuvant or adjuvant:vaccine, toxicology, stability testing, and pharmacokinetics/absorption, distribution, metabolism and excretion studies.

• Development of Timelines and Milestones for the proposed activities (may be revised during negotiations with NIAID if proposal deemed meritorious by the review panel).

Depending on the developmental stage at which an adjuvant is entered into the Program, the offeror may choose to propose additional IND-enabling studies. Examples of such studies are provided in Section III.1.C. DAIT: ADJUVANT DEVELOPMENT PROGRAM – Additional Technical Proposal Instructions, under 1.(b) of the Product Development Plan.

Technical Approach

A. For the purposes of this solicitation, proposals shall meet the following requirements:

1. Each proposal must focus on the development or further optimization of only one adjuvant candidate for one or more licensed or investigational vaccines.

2. Adjuvant studies must focus on one or more non-HIV disease pathogen(s) relevant to human disease.

3. The adjuvant has been previously identified as minimally reactogenic and characterized as safe after administration in an animal model. For example, safety could be documented by assessing acute morbidity/mortality, weight loss, injection site reactogenicity, pyrogenicity, respiratory distress or other related indicators of health in animals receiving the adjuvant.

4. Inclusion of data demonstrating that the adjuvant functions by stimulating the innate and/or adaptive immunity.

5. Inclusion of documented evidence demonstrating a mechanism of action for the adjuvant, such as activation of signal transduction pathways for dendritic cells, promotion of antibody production by B cells, or induction of Th1 or Th2 cytokines.

6. Documentation that the adjuvant safely augments the ability of a vaccine to protect against pathogen challenge in an in vivo animal model. The evidence of protection must be obtained from studies performed under well-controlled and documented experimental conditions, with a statistically significant better outcome than found under appropriate control conditions. If protection studies have not been conducted because appropriate containment facilities are not available, evidence of immune responses to the adjuvant that may be surrogates of immune responses for the protection in vivo will be acceptable.

7. Inclusion of data confirming that the adjuvant has immune-enhancing activity with human primary cells or tissues.

8. Documented evidence of access to all required materials and methods.

This contract will NOT provide funds to support the following activities:

• The further development of an adjuvant:vaccine candidate supported by the previous NIAID Adjuvant Development BAA-NIAID-DAIT-NIHAI2012146.

• The further development of an adjuvant that has been previously licensed in the U.S. for use with any vaccine.

• The development of adjuvants as stand-alone agents.

• The design and conduct of clinical trials (see http://clinicaltrials.gov/ct2/about-studies/glossary for the NIH definition of a clinical trial).

• The discovery and initial characterization of adjuvant candidates.

• More than one adjuvant in a proposal.

• The discovery or development of adjuvants or vaccines to prevent or treat cancer, allergic diseases or autoimmunity.

• Platform development such as vehicle or delivery systems.

• The development and/or optimization of a pathogen-specific vaccine component.

-- END OF RESEARCH AREA 001 --

C. DAIT: ADJUVANT DEVELOPMENT PROGRAM - Additional Technical Proposal Instructions:

The following information supplements Section IV – Instructions, Conditions, and Notices to Offerors, of this solicitation, and should be used for preparing proposals in response to Research Area 001. Separate and distinct proposals must be submitted for each Research Area to which you http://clinicaltrials.gov/ct2/about-studies/glossary are proposing. It is recommended that your proposal be organized in accordance with the order of your Statement of Work and the technical evaluation criteria provided in Section V.

(A) TECHNICAL APPROACH

Offerors may submit proposals for more than one adjuvant. However, separate Technical and Business Proposals are required for each adjuvant.

1. Product Development Plan

(a) Overview

Provide a summary of the Product Development Plan for the adjuvant selected for further development, outlining its intended use and specifications, approaches for carrying out each stage of the overall product development pathway, and clearly defined milestones and timelines necessary to complete and deliver an adjuvant suitable for future clinical studies within the 5-year contract performance period. Include a Gantt chart with tasks, milestones and decision gate criteria and also describe alternate strategies to address potential pitfalls.

(b) Product Development Activities

Although it is the responsibility of the Offeror to propose a Statement of Work, EXAMPLES of the types of product development activities that are within the scope of this BAA include:

1. Research and Development: design, conduct and complete non-clinical research and development studies to:

a. Evaluate the safety, pharmacokinetics/pharmacodynamics, bioavailability, formulation, dose, route of administration, and dose schedule of the adjuvant:vaccine, including in vitro and in vivo testing in an animal model(s), including non-human primates if appropriate, following FDA guidance and Good Laboratory Practice guidelines (GLP: as defined in the U.S. Code of Federal Regulations- 21CFR:58). FDA guidance for non-clinical studies may be found at the following site:

www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida nces/UCM292340.pdf. Animal studies must comply with the requirements as stated in the U.S. Code of Federal Regulations – CFR 601.90-95, Subpart H, “Approval of Biological Products When Human Efficacy Studies Are Not Ethical or Feasible.”

b. Develop, characterize, and qualify and/or validate reagents and assays required for evaluation of the adjuvant:vaccine.

c. Establish immunological parameters and methods to predict and evaluate safety and efficacy in vitro and for future use in human subjects.

d. Modify the adjuvant to improve its immunological activity and reduce potential toxicity in humans.

e. Demonstrate that the adjuvant has immune enhancing activity with human primary cells or tissues.

2. Process Development and Pilot Lot Manufacturing

a. Develop and establish master and working cell banks in compliance with current

Good Manufacturing Practices guidelines (cGMP: as defined in the U.S. Code of Federal Regulations-21 CFR:58, 210, 211, 610, 820 and applicable guidance’s, such as Draft Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals (1993) http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInfor mation/OtherRecommendationsforManufacturers/default.htm, see “Points to Consider”).

b. Conduct process development activities that lead to the manufacture of cGMP grade adjuvant and adjuvant:vaccine.

c. Establish a well-documented and controlled production process.

d. Manufacture non-cGMP pilot lots to demonstrate the reliability and reproducibility of the production process, and produce cGMP pilot lots of the adjuvant and the adjuvant:vaccine in amounts sufficient to carry out required non-clinical studies.

e. Conduct long-term stability studies of cGMP adjuvant or adjuvant:vaccine.

2. Statement of Work:

Describe the work requirements needed to advance a novel adjuvant:vaccine towards licensure for human use, including performance specifications.

(B) REGULATORY COMPLIANCE, QUALITY ASSURANCE AND DATA

MANAGEMENT SYSTEMS

As required for the implementation of the Product Development Plan, the Contractor shall:

1. Adhere to FDA regulations and guidance, including requirements for the conduct of animal studies and assays under GLP and the manufacturing of the adjuvant or adjuvant:vaccine under cGMP. The Contractor shall maintain quality assurance documentation to support adherence in these areas.

2. Arrange for independent regulatory audits, as needed or as requested by the Contracting Officer’s Representative and the Contracting Officer. Audits may be requested to ensure that Contractor and/or subcontractor facilities and all planned procedures comply with the FDA regulations and guidance that are required to meet GLP and cGMP standards. All Contractor and/or subcontractor records and staff shall be available for site visits or audits.

The Contractor shall provide interim and final audit reports to the Contracting Officer’s Representative and the Contracting Officer within thirty (30) calendar days of the completion of the audit. The NIAID reserves the right to conduct independent audits of the Contractor and its subcontractors as to evaluate compliance with the FDA regulations and guidance, including those required to meet GLP and cGMP standards.

3. Develop and implement data management and quality control systems/procedures, including the transmission, storage, confidentiality, and retrieval of all study data.

4. Provide statistical design and analysis of data resulting from the research undertaken.

5. Provide raw data or specific analyses of data generated with contract funding to the Contracting Officer’s Representative.

(C) SCIENTIFIC AND TECHNICAL PERSONNEL

The Contractor shall provide a scientific and technical team of investigators with the expertise needed for the management and implementation of the Product Development Plan to be performed under this contract, including research, manufacturing, regulatory, statistical, management, and administrative activities. The Contractor’s team must include strong scientific leadership, as well as significant experience and expertise in the management, design, and execution of a research and development program focused on product development, manufacturing, and testing in vertebrate animals. Also to be included is a Principal Investigator with responsibility for project oversight.

(D) PROJECT MANAGEMENT

The Technical Proposal must include a Project Management Plan addressing the following:

1. Include a Project Manager with responsibility for monitoring and tracking day-to-day progress and timelines, and coordinating communication, project activities, projects undertaken by subcontractors, and costs incurred.

2. Describe how the project will be staffed, organized, and managed, including a detailed description of the responsibilities for all proposed administrative personnel who will be assigned to the contract, and an administrative framework indicating clear lines of authority and responsibility for all personnel including proposed subcontractors and consultants.

3. Describe project management systems that will be used to track activities and to keep multiple activities on time and budget.

4. Outline how the PI will communicate and interact with the Contracting Officer’s Representative and the Contracting Officer and how the PI will communicate, monitor, and manage the project both internally and externally (at subcontractor facilities).

5. Provide a plan for soliciting, evaluating, negotiating, awarding, and managing any proposed subcontracts in accordance with FAR Clause 52.244-2.

6. Describe experience and education of contract management staff in the acquisition and management of subcontracts under Federal contracts.

7. Describe experience with identification and remediation of subcontractor performance problems or noncompliance with subcontract terms and conditions.

8. Provide documentation that the offeror has intellectual property protection and/or proprietary freedom to develop the adjuvant:vaccine.

(E) FACILITIES, EQUIPMENT, TRAINING AND OTHER RESOURCES

1. The Contractor shall provide the equipment, facilities, training and other resources required to implement the Product Development Plan in compliance with all Federal and NIH regulations. Depending on the stage of development of the adjuvant, this may include:

a. The performance of IND-enabling assays and animal studies under GLP.

Production, characterization and release testing of the adjuvant or the adjuvant:vaccine under cGMP conditions.

b. The care and housing of laboratory animals, including appropriate veterinary coverage, the physical plant housing all animals and laboratories, and required safety and security procedures.

c. Adherence to NIH regulations on human subjects research.

d. The use of facilities and resources to conduct work in accordance with the

Biosafety Level (BSL) 2 and 3 guidelines (http://www.cdc.gov/biosafety/) and in accordance with the Biosafety in Microbiology and Biomedical Laboratories (BMBL) Guidelines, Centers for Disease Control and Prevention and the National Institutes of Health, fifth Edition (http://www.cdc.gov/biosafety/publications/index.htm).

e. The handling, storing, and shipping of potentially dangerous biological and chemical agents, including Select Agents, under biosafety levels required for working with the biological agents under study. The Biosafety in Microbiology and Biomedical Laboratories, 5th edition is available at:

http://www.cdc.gov/biosafety/publications/index.htm. The Centers for Disease Control and Prevention (CDC) Select Agent program can be found at:

http://www.selectagents.gov/.

2. The Contractor is required to undertake all studies with approval from its

Institutional Biosafety Committee. The Contractor shall provide copies of materials submitted for Institutional Biosafety Committee Review and documentation of approval of experiments to the Contracting Officer’s Representative with each annual report.

(F) CONTRACT REVIEW MEETINGS

1. Annual Review Meetings

Annually, the Contracting Officer’s Representative will plan, conduct and be responsible for logistical arrangements for an annual review meeting of all Contractors, to be held at a site chosen by the Contracting Officer’s Representative. All Contractor PIs, Project Managers, key investigators including subcontractor personnel, the Contracting Officer’s Representative, the Contracting Officer, and other designated NIAID staff shall attend these meetings. The Contracting Officer’s Representative may invite other Extramural Program Staff from NIH to attend these meetings. The agenda will be prepared by the Contracting Officer’s Representative. Meetings will be closed to the general public and shall involve oral and electronic presentations by the Contractors, including: updates on results of activities undertaken or completed since the last review meeting; updates on the predicted timeline, including an updated Gantt chart; a description of any problems encountered or anticipated; a discussion of approaches to overcoming problems; and a description of activities to be undertaken in the coming year.

2. Site Visits

Within sixty (60) calendar days of the effective date of the contract, the Contractor shall plan, conduct and be responsible for the logistical arrangements for a post award kickoff http://www.cdc.gov/biosafety/ http://www.cdc.gov/biosafety/publications/index.htm http://www.cdc.gov/biosafety/publications/index.htm http://www.selectagents.gov/ meeting at the Contractor’s site. The Principal Investigator, Project Manager, all key investigators, key subcontractor personnel, the Contracting Officer’s Representative and the Contracting Officer shall attend this meeting. Other NIAID staff, as designated by the Contracting Officer’s Representative, may also attend this meeting. The purpose of this meeting shall be to review the Product Development Plan and to coordinate activities and communication between the Contractor and the NIAID. The Principal Investigator shall provide a copy of any slide presentations to the Contracting Officer’s Representative. The Contracting Officer and Contracting Officer’s Representative may request site visits at the Contractor site(s) annually or as needed.

3. Quarterly Teleconferences

The Contractor shall plan and conduct a teleconference meeting with the Contracting Officer’s Representative each quarter of the contract period of performance, to discuss technical progress and financial invoices. One (1) week prior to the teleconference, the Contractor shall submit an agenda to the Contracting Officer’s Representative. Within one (1) week after the teleconference, the Contractor shall provide a meeting summary of the teleconference to the Contracting Officer’s Representative. The timing of the Quarterly Teleconference meetings may be altered or adjusted by the Contracting Officer’s Representative as needed to address progress on the contract.

4. Additional Contract Meetings/Teleconferences

The Principal Investigator, Project Manager, key investigators, and key subcontractor personnel shall attend additional meetings or teleconferences at the request of the Contracting Officer’s Representative. Such meetings will be requested, as necessary, to discuss contract specific issues and to review recommended changes or deviations from milestones and timelines in the Product Development Plan.

5. Uniform Cost Assumptions

Offerors should use the following assumptions for the purposes of estimating costs and preparing the technical proposal:

a. Technical Cost Assumptions

1. Business Proposals must provide a breakdown by line item cost, including: Direct Labor, Direct Materials, Animal costs (including housing), Subcontracts, Consultants, Travel (refer to the instructions in Section IV, 2., C. - Business Proposal Instructions, of this solicitation).

2. It is anticipated that this contract will be aligned with the deliverables identified in the Research and Technical Objectives. Consequently, Business Proposals must provide a breakdown of costs for each milestone as well as a cost estimate for the entire project period of performance. The Business Proposal must also include a detailed Gantt chart that provides timelines delineating each milestone and associated tasks, subtasks and budgets to the subtask level of detail.

b. Travel

1. Annual Meeting: Assume (required) annual 1 day programmatic meeting in years 1- 4 of the contract, to be held in the Rockville, MD area, back-to-back with the 11/2 day annual meeting of the NIAID Adjuvant Development Program (attendance at Adjuvant Development Program’s annual meeting is optional for Adjuvant Development contractors). Include travel costs (transportation, meals, hotel, etc.)

for Contractor staff members, including the Principal Investigator, key co-investigators, collaborators and subcontractors (up to 7 individuals).

2. Subcontractor Site Visits: Budget travel costs (transportation, meals, hotels, etc.)

for two 2-day trips per year for up to 3 personnel to visit sites of subcontracts, if applicable.

D. DAIT: ADJUVANT DEVELOPMENT PROGRAM - Reporting Requirements and Deliverables:

1. Reporting Requirements

In addition to reporting requirements and deliverables identified elsewhere in this solicitation, it is expected that awards resulting from Research Area 001 will include the following reports and deliverables:

a. Semi-Annual Technical Progress Reports

This report is to include a summation of the work performed and the results obtained for the contract period of performance. This report shall be in sufficient detail to describe the results achieved, including any difficulties encountered and proposed or implemented remedies.

b. Final Report

This report is to include a summation of the work performed and the results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Final Report shall be submitted in accordance with the DELIVERIES Article in SECTION F of the contract. A Semi-Annual Progress Report will not be required for the period when the Final Report is due.

The Contractor shall provide the Contracting Officer’s Representative and Contracting Officer with one electronic copy each of the Final Report in draft form in accordance with the DELIVERIES Article in SECTION F of this contract 60 calendar days prior to the completion date of this contract. The Contracting Officer’s Representative will review the draft report and provide the Contracting Officer with comments within 30 calendar days after receipt. The Final Report shall be corrected by the Contractor, if necessary and the final version delivered as specified in the above paragraph.

c. Summary of Salient Results.

The Contractor shall submit, with the Final Report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract.

d. Report on Select Agents or Toxins and/or Highly Pathogenic Agents

The Contractor shall describe what agents or toxins were used, if any, and list the studies conducted with them.

2. Deliverables

Delivery of other reports and deliverables will be proposed by the Offerors in their technical proposal. They will be developed further after receipt of proposals as a result of finalization of the Statement of Work and other terms and conditions of any resultant contract during negotiations.

All electronic reports and deliverables shall be submitted through the NIAID Electronic Reports and Deliverables System, available here: https://erds.niaid.nih.gov/

-- END OF DAIT: ADJUVANT DEVELOPMENT PROGRAM --

2. DIVISION OF ALLERGY, IMMUNOLOGY, AND TRANSPLANTATION (DAIT),

RADIATION/NUCLEAR COUNTERMEASURES PROGRAM

Over the last three decades, world events have highlighted the growing threat of terrorism and its many forms, including the 1995 Tokyo sarin gas attack; radiological dispersal devices (dirty bombs) planted, but never detonated in Chechnya in 1995 and 1998; and the deliberate spread of anthrax spores and ricin through the United States postal service in 2001 and 2003, respectively. These incidents provide insight into the range of approaches used by terrorists, which include the potential to use chemical, biological, and/or radiological/nuclear weapons. Acts of radiological or nuclear terrorism could involve the use of stolen or improvised nuclear devices, attacks on nuclear power plants or reactors, the detonation of a dirty bomb, or the placement of radiation sources in public locations or in food or water supplies. Moreover, natural disasters like the 2011 earthquake and tsunami in Japan, which resulted in damage to the Fukushima Daiichi Nuclear Power Plant, and release of radiation into the environment, further emphasize the need for the United States Government to be prepared with stockpiled medical countermeasures (MCMs, e.g. drugs and/or biodosimetry devices) to be used in the event of a radiation incident.

Radiation/nuclear incidents and disasters can potentially result in the large-scale exposure of civilian populations to a high dose of radiation in a short period of time, which may lead to Acute Radiation Syndrome (ARS). Depending on the dose of whole-body exposure to radiation, biological effects can range from acute effects, including nausea and vomiting within hours; hematopoietic and gastrointestinal injury leading to immunosuppression, infection, hemorrhage and death within days to weeks (ARS); to late lung, cardiovascular, and kidney complications months after irradiation (delayed effects of acute radiation exposure or DEARE).

The United States Government recognizes the need to develop MCMs to address the systemic damage from radiation exposure following a radiological/nuclear incident. To this end, the Project BioShield Act of 2004, “Project BioShield”, Public Law 108-276, was enacted on July 21, 2004.

The Act provides the Department of Health and Human Services (HHS) with authorities to procure MCMs for the Strategic National Stockpile (SNS) and to perform advanced research and development on priority MCMs against chemical, biological, radiological, and nuclear threats.

Under this act, the National Institute of Allergy and Infectious Diseases (NIAID) Radiation and Nuclear Countermeasures Program (RNCP) was charged by HHS, on behalf of the National Institutes of Health (NIH), to address radiation-induced injuries resulting from a radiological/nuclear incident, with funds provided from a special congressional appropriation.

The coordinated efforts to support research and development of MCMs by the NIH, as well as other HHS sister agencies, is outlined in the HHS Public Health Emergency Medical Countermeasures https://erds.niaid.nih.gov/ http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx

Enterprise (PHEMCE) implementation plan. The NIH is committed to accelerating the development of both medical approaches to treat injuries, and biodosimetry biomarkers and/or devices, for triage use in mass casualty situations, and supporting advanced development and deployment efforts to make them available for possible procurement by the Biomedical Advanced Research and Development Authority (BARDA) and subsequent storage in the SNS, overseen by the Centers for Disease Control and Prevention (CDC).

In 2005, based on the recommendations of a Blue Ribbon Panel, NIAID published its Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats, which was most recently updated in 2012. These plans describe a multifaceted program to expand research infrastructure and radiobiology expertise; promote the development of biodosimetry methods to assess radiation injury; and research, identify, develop, and obtain licensure for MCMs to mitigate/treat radiation-induced injuries, in order to save lives during a radiation emergency.

The goal of Research Area 002, below, is to support the development of safe and effective MCMs to mitigate and/or treat tissue injuries arising from exposure to ionizing radiation from a radiological or nuclear incident, thereby leading to a reduction in radiation-associated morbidities and mortalities.

Since the program’s inception, NIAID has sponsored early-stage/applied research, product development programs and targeted initiatives focused on development of drugs to mitigate and/or treat complications of ARS and DEARE syndromes (e.g. hematopoietic, gastrointestinal, pulmonary, renal, central nervous system, cutaneous, and radiation combined injury). Investment in this portfolio has led to the establishment of several rodent and non-human primate animal models which are critical for licensure of radiation mitigators under the U.S. Food and Drug Administration (FDA) Animal Rule. In fact, studies funded by the RNCP led to FDA approval of both Neupogen® (filgrastim) and Neulasta® (pegfilgrastim) for the adult and pediatric hematopoietic-ARS indication in March 2015 and November 2015, respectively. Although progress has been made in licensing products to treat some forms of radiation injury, drugs are still needed to address other forms of hematopoietic injury, as well as for the treatment of other organ systems affected by radiation exposure.

The goal of Research Area 003, below, is to advance the development and translation of biodosimetry biomarkers and/or devices to inform triage and treatment strategies for a mass casualty radiation incident.

The number of casualties from a radiological or nuclear incident could can result in many persons exposed to radioactive fallout downwind from the explosion. Such victims might not initially show clear signs and symptoms of radiation toxicity, even if exposed to substantial doses of radiation.

Similarly, persons exposed to a radiological dispersal device might also present minimal evidence of exposure. In addition, person-to-person variability must be considered in early and delayed radiation damage to organs and tissues in response to a given radiation dose. Confounding factors include genetic pre-disposition, age, body size, underlying illnesses, and immune status. Therefore, estimates of radiation exposure dose alone will not necessarily predict the extent of radiation injury to organs and tissues. Hence, the need for rapid, accurate and sensitive biomarker assays/techniques and diagnostic platforms that can confirm exposure and predict acute and delayed radiation injury to different organs and tissues in victims of radiation incidents.

Existing biodosimetry techniques and devices, and others in development, cannot assess biological variability. In addition, these techniques and devices do not predict the severity of injury sustained by specific organs and tissues, and thus do not allow for the prompt organ- and tissue-directed medical treatment that might be provided by any available radiation MCMs. With the potential of a http://www.phe.gov/Preparedness/mcm/phemce/Pages/strategy.aspx https://www.niaid.nih.gov/sites/default/files/radnucstrategicplan.pdf https://www.niaid.nih.gov/sites/default/files/radnucstrategicplan.pdf https://www.niaid.nih.gov/sites/default/files/radnucprogressreport.pdf mass casualty occurring, the measurement of absorbed radiation dose (biodosimetry) is needed to better inform health care and first responders on the appropriate triage and treatment strategies following a radiological or nuclear incident, in order to facilitate precise and timely medical intervention, reduce morbidity, and save lives.

B. RESEARCH AREAS (DAIT: RADIATION/NUCLEAR COUNTERMEASURES PROGRAM)

Research Area 002 - Development of Radiation/Nuclear Medical Countermeasures .

NIAID anticipates that one or two awards may be issued for a total cost of up to $2 million for the non-severable base work across all contracts (direct and indirect costs combined), depending on the number of technically meritorious proposals, importance to agency programs, and availability of funds. The total cost for each award(s) may vary depending upon the scope of the project and the technical objectives of the award(s).

The total duration of a proposed contract should be consistent with the nature and complexity of the offeror’s proposed research. The total performance period comprised of the base and any options proposed by an Offeror should not exceed three (3) years.

Awards are anticipated to be made in or around April 2018.

Offerors are invited to submit proposals to advance the development of one lead candidate MCM that has shown concept feasibility. MCM candidates should increase survival by mitigating and/or treating acute or delayed radiation injury.

Proposals should include a plan to conduct translational research and development and, if applicable, provide additional information and data to support U.S. Food and Drug Administration (FDA) approval or licensure and submission of an Investigational New Drug (IND) application. Offerors should include a well-defined product development path that includes IND-enabling studies that will be performed under the contract.

Specifically, this Research Area is intended to support the research and development of promising new approaches to mitigate and/or treat tissue injuries arising from exposure to ionizing radiation, which may include, but are not limited to: biologics, including cytokines and free radical scavengers; cellular therapies; and drugs, such as, anti-inflammatory agents, antibiotics, and anti-fibrotics.

The lead MCM to be supported by this initiative must meet all of the following scientific and technical requirements prior to submission of the proposal:

1. The lead MCM should already have demonstrated efficacy (i.e., demonstrating clinically-relevant and statistically-significant reduction in mortality and/or major morbidity in animal models of acute or delayed radiation injury predictive of the human response) when administered at least 24 hours after radiation exposure. The MCM preferably should be easy to distribute and use in a mass casualty incident (e.g., the preferred routes of administration are oral, subcutaneous, inhaled, transdermal or intramuscular);

2. The lead MCM should be safe to use in normal, healthy individuals if appropriate biodosimetry is not available to confirm radiation dose received prior to initiating treatment). The lead MCM should be previously identified as minimally reactogenic using animal model safety studies and/or in human clinical studies for another indication. For example, safety could be documented by assessing acute morbidity/mortality, weight loss, injection site reactogenicity, pyrogenicity, respiratory distress or other related indicators of health;

3. Radiation exposure type, dose level, and dose rates proposed for study need to be relevant to a terrorist incident or accidental exposure. Studies using fractionated radiation exposures, commonly used for clinical radiotherapy treatments would NOT be appropriate, unless information gained would be directly applicable to an unintentional exposure scenario; and

4. A target product profile for the lead MCM that includes:

a. Preliminary data to support the selection of the MCM, specifically: animal studies that demonstrate efficacy when delivered 24 hours or later after radiation exposure using appropriate animal models and assays.

b. Safety studies and PK/PD studies, if any.

c. Intended use/indication of the lead MCM and the biodefense/public health gap that the product is intended to fill.

d. The performance specifications and features the MCM would meet in order to provide therapeutic benefit.

e. Physicochemical characteristics, current formulation, and a mechanism of action, if known.

f. Discussions or meeting minutes with the FDA, if any, that are relevant to development activities for the proposed therapeutic product.

This contract will provide funds to support the following activities:

1. Non-clinical Research and Development, including:

a. Animal model(s) development.

b. Reagent and assay development.

c. Efficacy studies in animals to optimize route of administration, formulation, dose, dose schedule, and dose modifying factor (DMF). Studies should be designed to be suitable (species, endpoints, measurements) for predicting future pivotal Good Laboratory Practice (GLP) efficacy studies under the FDA Animal Rule (21 CFR 314.600-314.650, 601.90- 601.95). Efficacy is defined hereafter as a statistically significant improvement in survival in an in vivo model of radiation injury when the MCM is first administered at least 24 hours or later after radiation exposure.

d. Efficacy studies to test the lead MCM in the context of other expected medical management, including growth factors.

e. Mechanism of action studies.

f. Bioavailability; pharmacokinetic; and adsorption, distribution, metabolism, and…