BAA-18-100-SOL-00003_Amendment_1.pdf

Office of Biomedical Advanced Research and Development Authority (BARDA) Broad Agency Announcement (BAA)

BAA-18-100-SOL-00003

Amendment 1 June 15, 2018

Office of Acquisitions Management, Contracts, and Grants (AMCG)

200 C Street SW

Washington, DC 20201

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Table of Contents

Office of Biomedical Advanced Research and Development Authority (BARDA) Broad Agency Announcement (BAA)

INTRODUCTION

OVERVIEW INFORMATION

Agency Name:

Issuing Office:

Development Opportunity Title:

Announcement Type and Date:

Eligible Offerors:

Research and Development Opportunity Description:

Research and Development Areas of Interest:

Technological Maturity:

Number of Awards:

Type of Award:

Application Process:

Submission Deadlines and Government Response Time:

Contact and Submission Information:

Limitation on Communication After Submission:

Preliminary Inquiries:

TechWatch Program:

Special Instructions:

Proposal Handling and Submission Information:

BACKGROUND

Part I: Research and Development Areas of Interest

Area of Interest #1: CBRN Vaccines Area of Interest #2: CBRN Antitoxins and Therapeutic Proteins Area of Interest #3: Antibacterials Area of Interest #4: Radiological/Nuclear Threat Medical Countermeasures Area of Interest #5: Chemical Threat Medical Countermeasures Area of Interest #6: Burn Medical Countermeasures Area of Interest #7: Diagnostics Area of Interest #8: Influenza and Emerging Infectious Diseases (IEID) Vaccines Area of Interest #9: Influenza and Emerging Infectious Diseases (IEID) Therapeutics Area of Interest #10: Respiratory Protective Devices Area of Interest #11: Ventilators Area of Interest #12: MCM Production Platform Systems Area of Interest #13: Modeling as an Enabling Technology for Influenza, Emerging Infectious Disease, and CBRN Threats Area of Interest #14: Visual Analytics an Enabling Technology for

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Influenza, Emerging Infectious Disease, and CBRN Threats Part II: Development and Technical Objectives

Program Management Approach:

Regulatory Approach:

Development and Manufacturing Approach:

Part III: Reporting Requirements and Deliverables Reports:

Meetings:

Regulatory and Quality Management:

Audits / Site Visits:

Program Management Plans and Documentation:

Part IV: Special Considerations A. Contractor Responsibility Regarding Sensitive Information:

B. Security Plan:

C. Identification and Disposition of Data:

D. Confidentiality of Information:

E. Publications:

F. Press Releases:

G. Export Control Notification:

H. Manufacturing Standards:

I. Prohibition on Contractor Involvement with Terrorist Activities:

J. Invoices:

Part V: Quad Chart/White Paper Instructions (Stage 1) Stage 1: Quad Chart and White Paper Preparation Quad Chart and White Paper Submission Chart and White Paper Review

Part VI: Full Proposal Instructions (Stage 2) Stage 2: Full Proposal Instructions Volume I – Technical Proposal Volume I - Technical Proposal Attachments Volume II – Cost Proposal Volume II - Cost Proposal Attachments Stage 2: Full Proposal Submission

Part VII: Quad Chart/White Paper and Full Proposal Evaluation A. Quad Chart/White Paper Evaluation Criteria B. Full Proposal Evaluation Criteria C. Other Evaluation Factors and Considerations D. Evaluation Rating E. Additional Information

Part VIII: Attachments Attachment 1: Technology Readiness Level Criteria Attachment 2: Target Product Profile Template Attachment 3: Regulatory Guidance for Devices Including Diagnostics 102 Attachment 4: Summary of Related Activities Attachment 5: Quad Chart Format Template Attachment 6: Government Notice for Handling and Submitting Proposals

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Attachment 7: Breakdown of Proposed Estimated Cost (Plus Fee) and Labor Hours (For Cost Proposal) Attachment 8: Cost Certification

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INTRODUCTION

This Broad Agency Announcement (BAA), which sets forth research and development (R&D) areas of interest (AOI) for the Office of Biomedical Advanced Research and Development Authority (BARDA), is issued under paragraph 6.102(d)(2)(i) of the Federal Acquisition Regulation (FAR). Proposals selected for award are considered to be the result of full and open competition and in full compliance with 41 U.S.C. § 3301. A formal Request for Proposal will not be issued. Paper copies of this announcement will not be issued. The U.S. Government (Government) reserves the right to select for award and fund all, some, or none of the proposals in response to this announcement. All proposals will be treated as sensitive competitive information and the contents only disclosed for the purpose of evaluation.

Offerors that are not responsive to the Government requests for information in a timely manner, defined as meeting government deadlines established and communicated with the request, may be removed from award consideration.

The Government reserves the right to award the instrument best suited to the nature of the research proposed and may award any appropriate contract type under the FAR.

OVERVIEW INFORMATION

Agency Name:

U.S. Department of Health and Human Services (HHS), Office of the Secretary, Office of the Assistant Secretary for Preparedness and Response (ASPR), Office of Biomedical Advanced Research and Development Authority (BARDA), 200 C Street SW, Washington, DC, 20201

Issuing Office:

Department of Health and Human Services (HHS), Office of the Secretary (OS), Office of the Assistant Secretary for Preparedness and Response (ASPR), Office of Acquisitions Management, Contracts, and Grants (AMCG), 200 C Street SW, Washington, DC, 20201

Development Opportunity Title:

Office of Biomedical Advanced Research and Development Authority (BARDA) Broad Agency Announcement (BAA)

Announcement Type and Date:

Broad Agency Announcement, November 6, 2017 as: BAA-18-100-SOL-00003

This Broad Agency Announcement combines versions of three related Broad Agency Announcements (BARDA CBRN BAA, BARDA Influenza BAA, and BARDA SST BAA), which have been re-issued annually.

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This BAA is available on the following websites:

• Federal Business Opportunities - FBO.gov1

• MedicalCountermeasures.gov2

• Public Health Emergency - PHE.gov3

• Grants.gov4

Amendments to this BAA will be posted to the websites listed above when they occur.

Interested parties are encouraged to check these websites periodically for updates and amendments.

Eligible Offerors:

This BAA is open to ALL responsible sources. Offerors may include single entities or teams from private sector organizations, Government laboratories, and academic institutions.

To be eligible for award, a prospective recipient must meet certain minimum standards pertaining to financial resources, ability to comply with the performance schedule, prior record of performance, integrity, organization, experience, operational controls, technical controls, technical skills, facilities, and equipment.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they address the following conditions. FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector AND must provide a letter on letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to government solicitations and compete with industry, and compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be primes or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority (as well as, where relevant, contractual authority) establishing their ability to propose to government solicitations. Specific supporting regulatory guidance, together with evidence of agency approval will be required to establish eligibility. BARDA will consider eligibility submissions on a case-by-case basis;

however, the burden to prove eligibility for all team members rests solely with the Proposer.

Historically Black Colleges and Universities (HBCU), Minority Institutions (MI), Small Business concerns, Small Disadvantaged Business concerns, Women-Owned Small Business concerns, Veteran-Owned Small Business concerns, Service-Disabled Veteran-Owned Small Business concerns, and HUB Zone Small Business concerns are

1 https://www.fbo.gov/ 2 https://www.medicalcountermeasures.gov/ 3 http://www.phe.gov/ 4 http://www.grants.gov/ https://www.fbo.gov/ https://www.medicalcountermeasures.gov/ http://www.phe.gov/ http://www.grants.gov/

BARDA BAA-18-100-SOL-00003 Amendment 1 Page 7 encouraged to submit proposals and to join other entities as team members in submitting proposals.

In accordance with federal statutes, regulations, and U.S. Department of Health and Human Services (HHS) policies, no person on grounds of race, color, age, sex, national origin, or disability shall be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any program or activity receiving financial assistance from the HHS.

Research and Development Opportunity Description:

The Office of Acquisitions Management, Contracts, and Grants (AMCG) on behalf of the Office of Biomedical Advanced Research and Development Authority (BARDA) solicits proposals for the advanced research and development of medical countermeasures (MCM) for chemical, biological, radiological and nuclear (CBRN) agents, pandemic influenza, and emerging infectious diseases that threaten the U.S. civilian population.

BARDA anticipates that R&D activities awarded under this BAA will serve to advance candidate medical countermeasures towards licensure or approval by the U.S. Food and Drug Administration (FDA). This BAA will also serve to advance the knowledge and scientific understanding of candidates’ platform technologies, modeling and forecasting, and visual analytics.

The purpose of this BAA is to solicit proposals that focus on research and development in the following solicited AOI as listed here and further described in Part I of this announcement. The BAA does not support the acquisition of products or the construction of facilities.

Research and Development Areas of Interest:

Development and technical objectives are described in Part II. Efforts proposed by Offerors may cover all aspects of MCM Advanced Research and Development, including Non-Clinical Research and Development, Process Development, Platform Development, Formulation, Manufacturing, and Clinical Evaluation.

Technological Maturity:

Offerors must identify in their Quad Chart and White Paper the current Technology Readiness Level (TRL) of their product, and the TRL identified should meet or exceed the requirements of the given Development Area of Interest. Each White Paper should also contain sufficient supporting information and data to justify the TRL rating. Criteria for determining the appropriate TRL for a product can be found in Attachment 1. Note that all activities within a TRL (or sublevel) must be completed to have achieved that TRL status. One TRL criteria document is provided for use with diagnostics and medical devices (Attachment 1A) and one TRL criteria document is provided for use with therapeutics and vaccines (Attachment 1B). TRL requirements for enabling technologies or products that are not directly applicable to the TRL criteria will be considered on a case-by-case basis.

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Number of Awards:

Multiple awards of various values are anticipated and are dependent upon the program priorities, proposals’ scientific/technical merits, how well the proposals fit BARDA’s areas of interest, and available funds. Anticipated funding for the program is subject to congressional appropriations. The program funding is subject to change due to government discretion and funding availability.

Type of Award:

A contract award under this BAA may utilize Cost-Reimbursement, including Cost (C), Cost-Sharing (CS), Cost-Plus-Incentive-Fee (CPIF), and Cost-Plus-Fixed-Fee (CPFF) Contracts, and Firm-Fixed-Price (FFP) Contracts.

Offerors submitting Full Proposals should submit cost-sharing contract (or cost contract) proposals. When cost sharing is proposed, the amount of cost participation should depend on the extent to which the R&D effort or results are likely to enhance the Offeror’s expertise, capability, or competitive position.

If an Offeror does not believe that a Cost-Sharing contract (see FAR 16.303) (or Cost contract [see FAR 16.302]) is appropriate, then the Offeror should provide the reason in writing under “B. Basic Cost/Price Information” of the Cost Proposal (Part VI, Stage 2, Volume II – Cost Proposal Attachments). The reason should include an explanation (i) as to why there is no probability that the Offeror would receive any present or future benefits from an award, (ii) of the R&D expected to be of only minor value to the Offeror, or (iii) of a statute that precludes the use of cost sharing.

If the Government contemplates the award of a cost-reimbursement type contract, the Offeror must demonstrate prior to award that its accounting system is adequate for administering a cost-reimbursement contract. Offerors should propose the type of arrangement they believe best satisfies the requirement.

The Government may also elect to make awards in the form of grants and cooperative agreements, and Other Transactions (OT) agreements, as authorized for BARDA under the Pandemic and All Hazards Preparedness Reauthorization Act (2013).

The costs of preparing responses to this BAA are not considered an allowable direct charge on any resultant award.

Application Process:

Stage 1: Prepare a cover sheet, Quad Chart, and White Paper in accordance with the preparation guidance. Offerors must submit their Quad Chart and White Paper in accordance with the instructions provided in Part V. The Quad Chart and White Paper should describe the effort in sufficient detail to allow evaluation of the concept's technical merit and its potential contribution to the BARDA mission. BARDA will evaluate White Papers based on the criteria provided in Part VII.

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Offerors whose Quad Chart and White Paper receive a favorable evaluation will be invited via e-mail to submit a Full Proposal. Offerors whose Quad Chart and White Paper did not receive a favorable evaluation will be notified via e-mail, and will be provided with information on technical issues and concerns that BARDA has regarding the proposed product. This written feedback is the only response that will be provided to unsuccessful Stage 1 Offerors.

Stage 2: Offerors must submit their Full Proposals in accordance with the instructions provided in Part VI. Full Proposals will be evaluated against criteria as described in Part VII. Proposals that do not conform to the requirements outlined in the BAA or to the instructions provided in the invitation letter will not be considered for further action.

Submission Deadlines and Government Response Time:

Table 1: Submission Deadlines and Government Response Time

Proposal Stage Deadline for Submission* Government Response Stage 1: Quad Chart and White Paper

A Quad Chart and White Paper may be submitted on any day during the open period of the BAA. Submission deadlines are as follows:

January 31, 2018 April 30, 2018 July 31, 2018 October 31, 2018 January 31, 2019 April 30, 2019 July 31, 2019 October 31, 2019

The final White Paper submission deadline is October 31, 2019.

A receipt confirmation will be sent within 1 week.

A decision will be made within 90 calendar days of the submission deadline.

Stage 2: Full Proposal As specified in the Invitation Letter.

A Full Proposal may be submitted on any day during the open period of the BAA.

Full Proposal submission deadline is October 31, 2019.

A receipt confirmation will be sent within 1 week.

A decision will be made within 90 calendar days of receipt of Full Proposal.

*Submissions must be submitted no later than 4:30 PM Eastern Standard Time for each due date.

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Contact and Submission Information:

All inquiries and submissions regarding this BAA must be sent to:

BARDA-BAA@hhs.gov.

Technical questions only should be directed to the Technical Point of Contacts (POC) listed under each area of interest. The Technical POCs are located in “Part I: Research and Development Areas of Interest.”

Limitation on Communication After Submission:

Be advised that after a White Paper (or Full Proposal) has been submitted, all communications related to that submission must be through the Contracting Office at BARDA-BAA@hhs.gov. Communications following the Government response to a White Paper or Full Proposal submission must be through the Contracting Officer identified in the response letter.

When submitting a Full Proposal following receipt of White Paper Response Letter from the Contracting Officer, submit the Full Proposal to BARDA-BAA@hhs.gov, carbon copy (cc) the Contracting Officer, and reference the Response Letter in the first paragraph of the email.

Do not cc or blind carbon copy (bcc) the technical POCs or any other individuals within Program during submission of a Full Proposal. Similarly, do not cc or bcc the technical POCs or any other individuals within Program when sending inquires to BARDA-BAA@hhs.gov or directly to the Contracting Officer.

Preliminary Inquiries:

The Government realizes that the preparation of a development proposal often represents a substantial investment of time and effort by the Offeror. In an attempt to minimize this burden, BARDA encourages organizations and individuals interested in submitting proposals to make preliminary inquiries as to the general need for the type of R&D effort contemplated before expending extensive effort in preparing a detailed proposal or submitting proprietary information.

TechWatch Program:

Offerors are encouraged to participate in the TechWatch program prior to any White Paper or Full Proposal submissions. Participation in the TechWatch program affords Offerors an opportunity to present their capabilities to BARDA scientific subject matter experts and program managers, as well as Office of Acquisitions Management, Contracts, and Grants (AMCG) acquisition professionals. These personnel can evaluate products/technologies, suggest techniques and strategies for meeting technical and regulatory challenges, provide insight on how a product or technology may address BARDA's objectives, and provide general information about BARDA's mission and programs. To request a TechWatch meeting and for more information about the TechWatch program, Offerors should visit the TechWatch website5. Entities with a White

5 https://www.medicalcountermeasures.gov/barda/advancing-innovation/techwatch.aspx mailto:BARDA-BAA@hhs.gov mailto:BARDA-BAA@hhs.gov mailto:BARDA-BAA@hhs.gov mailto:BARDA-BAA@hhs.gov https://www.medicalcountermeasures.gov/barda/advancing-innovation/techwatch.aspx

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Paper or proposal currently under review under any ASPR solicitation are not eligible to schedule a TechWatch meeting related to that submission.

Special Instructions:

Special instructions will be advertised via the BAA as they become apparent. These additional instructions would be tailored to specific AOI and may have unique submission due dates. The information requested in these instructions should be used along with Part VI of the BAA to format and prepare the Technical (Volume I) and Cost (Volume II) Proposals. Offerors shall follow the instructions in Part VI of the BAA, and include the information requested therein.

Proposal Handling and Submission Information:

Treatment of Submission Documents: All proposals are treated as Offeror’s proprietary information prior to award and the contents are disclosed only for the purpose of evaluation. The Offeror must indicate any limitation to be placed on disclosure of information contained in the proposal in accordance with the instructions as set forth in FAR 52.215- 1(e) “Restrictions on disclosure and use of data.”

Classified Submissions: Classified proposals will not be accepted. All submissions must be Unclassified.

Use of Color Proposals: All proposals received shall be stored as electronic images.

Electronic color images require a significantly larger amount of storage space than black-and- white images. As a result, Offerors' use of color in proposals should be minimal and used only when necessary for details. Do not use color unless necessary.

Post-Employment Conflict of Interest: There are certain post-employment restrictions on former federal officers and employees, including special government employees (Section 207 of Title 18, U.S.C.). If a prospective Offeror believes a conflict of interest may exist, the situation should be emailed to the appropriate Contracting Officer, prior to expending time and effort in preparing a proposal. The appropriate HHS personnel will discuss any conflict of interest with prospective Offeror.

Unsuccessful Proposal Disposition: Proposals will not be returned. The original of each proposal received will be retained by ASPR pursuant to FAR 4.805 and all other non-required copies destroyed.

Government Notice for Handling and Submitting Proposals: Refer to Attachment 6 for inclusion requirement of the Government notice.

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BACKGROUND

This Broad Agency Announcement (BAA) sets forth advanced development areas of interest for the Office of Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the Office of the Secretary (OS) of the U.S. Department of Health and Human Services (HHS). This BAA is issued under paragraph 6.102(d)(2) of the Federal Acquisition Regulation (FAR), and proposals selected for award are considered to be the result of full and open competition and in full compliance with The Competition in Contracting Act of 1984, 41 U.S.C. 253.

BARDA is the lead federal agency for supporting advanced development of MCM to protect the United States against public health emergency threats, including CBRN agents, emerging infectious diseases, and pandemic influenza. The Pandemic and All Hazard Preparedness Reauthorization Act authorizes BARDA to promote (i) innovations in technologies that may assist MCM advanced research and development, (ii) research and development of tools, devices, and technologies, and (iii) research to promote strategic initiatives, such as rapid diagnostics, broad spectrum antimicrobials, and vaccine manufacturing technologies. The continuing threat of terrorism, pandemic influenza, and emerging diseases underscores the compelling need to develop new and improved MCM for protecting all segments of the civilian population. BARDA is soliciting proposals for the advanced research and development of MCM for CBRN agents; the ever-present and ever-evolving threat of novel influenza; and the re-emergence and emergence of infectious diseases that threaten the U.S. civilian population. This BAA will support the development of candidate products and diagnostic tools to meet the challenging requirements of CBRN MCM (e.g. post- exposure efficacy, extended shelf life, storage, distribution, and dispensing).

The priorities of the BARDA Influenza and Emerging Infectious Diseases Division are closely aligned with the Public Health Emergency Medical Countermeasures Enterprise Review6 (August 2010), the President’s Council of Advisors on Science and Technology’s Report to the President on Reengineering the Influenza Vaccine Production Enterprise to Meet the Challenges of Pandemic Influenza7 (August 2010), the BARDA Strategic Plan 2011-20168 (October 2011), and HHS Pandemic Influenza Plan9 (June 2017).

Vaccines, therapeutics, diagnostics, ventilators, and respiratory protective devices are essential for protecting all segments of the civilian population from pandemic influenza and other emerging infectious diseases. This BAA will support advanced development activities of medical countermeasures for influenza and other emerging respiratory viruses to be specified by BARDA. BARDA’s priority for influenza vaccines is sustainable, cost effective approaches that improve pandemic influenza preparedness and rapid response capabilities. BARDA’s strategy to address this priority includes 1) improve vaccine effectiveness; 2) modernize production processes to decrease response time; 3) increase and diversify the sustainable domestic vaccine manufacturing infrastructure; 4) develop new adjuvants, delivery approaches, and other strategies that

6 https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf 7 http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST-Influenza-Vaccinology-Report.pdf 8 https://www.medicalcountermeasures.gov/media/745/bardastrategicplan9-28--508.pdf 9 https://www.cdc.gov/flu/pandemic-resources/pdf/pan-flu-report-2017v2.pdf https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST-Influenza-Vaccinology-Report.pdf http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST-Influenza-Vaccinology-Report.pdf https://www.medicalcountermeasures.gov/media/745/bardastrategicplan9-28--508.pdf https://www.cdc.gov/flu/pandemic-resources/pdf/pan-flu-report-2017v2.pdf

BARDA BAA-18-100-SOL-00003 Amendment 1 Page 13 can provide a priming and protective response with a single vaccine dose and are more amenable to mass vaccinations in a response event. BARDA is also prioritizing broadly reactive immunotherapeutics, such as monoclonal antibodies, that will be effective in treating severely ill, hospitalized patients of all ages who are infected with influenza or in specific cases as described in subsequent sections, other emerging infectious diseases.

Such therapeutics will demonstrate effectiveness when given later than 48 hours after onset of symptoms. Additional focus will be placed on MCM and devices suitable for use in at-risk populations such as children, pregnant women, the elderly, and persons with compromised immune systems. BARDA will endeavor to prioritize projects that provide benefits to all populations, while also allowing for focused development projects or studies for at-risk populations where necessary.

BARDA’s CBRN priorities are aligned with the preparedness mission of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), as articulated in the 2016 PHEMCE Strategy and Implementation Plan10. Specifically, HHS has generally adopted a strategy of developing and acquiring MCM for post-event response to CBRN threats. Preventive measures are appropriate only for threats of such potential catastrophic consequence that a pre-event strategy will be examined in order to reduce vulnerability and mitigate post-event consequences. Currently, no pre-event MCM strategies are deemed necessary and feasible at this time for the U.S. civilian population. Therapeutics and diagnostics or the use of post-event prophylaxis will be the preferred strategy for all other threats. Priority will be placed on MCM that focus on post-event prophylaxis or post-exposure treatment. Some CBRN programs are reaching maturity and their intended goal, and receive less emphasis in this process. More emphasis will be placed upon product candidates that have multi-purpose indications (i.e., CBRN usage and commercial indication for public health needs). Additional focus will be placed on supporting the development of medical countermeasures suitable for use in special populations such as children, pregnant women, the elderly, and persons with compromised immune systems, prioritizing and supporting projects that provide benefits to all populations where possible and exploring focused development projects or studies where necessary. To that end, BARDA supports the advanced research and development, and acquisition of MCM such as vaccines, therapeutics, and diagnostics.

BARDA addresses the many challenges to the development of MCM that mitigate the effects of CBRN, pandemic influenza, and emerging infectious disease threats by leveraging commercial technologies, innovative methodologies, and resources used by academia and the private sector. BARDA invests where it has identified gaps or opportunities in technical capabilities that improve the execution of its mission, and is currently focusing on several enabling technologies: standardized technologies (platforms) for rapid MCM development; predictive modeling and novel quantitative analysis capabilities; and visual analytics tools. The refinement of existing platform technologies and the development of innovative new platform technologies for rapid response vaccine, therapeutic, and diagnostic development is an essential part of a paradigm shift in product development from a “one-off” to a “plug-and-play” approach, that can expedite the technical and regulatory path from threat identification to safe, effective human use. Predictive modeling and quantitative analysis plays a key role in determining how large a pandemic or CBRN incident may be and informing development and manufacturing of critical MCM to address the crisis. Visual analytics capabilities, applications, and tools allow visual access to increasingly larger and more complex data

10 https://www.medicalcountermeasures.gov/media/36937/2016_phemce_sip.pdf https://www.medicalcountermeasures.gov/media/36937/2016_phemce_sip.pdf

BARDA BAA-18-100-SOL-00003 Amendment 1 Page 14 sets in an easily understandable format to support the breadth of BARDA’s MCM product development.

Awards resulting from this BAA may also benefit from multiple core services that BARDA already provides and will provide in the future. These core services include an animal study network, flexible manufacturing facilities, and technical expertise in development, manufacturing, regulatory affairs, quality systems, and clinical studies.

For additional requirements information, visit:

• The Pandemic and All Hazard Preparedness Act11 Pub. L. No. 109-417, 42 U.S.C. § 241 et seq. (PAHPA) and

• The Pandemic and All Hazard Preparedness Reauthorization Act Pub. L. No.

113-512, (PAHPRA).

Learn more about legal authorities, policies, and committees13 and strategies and reports14 for pandemic influenza, Chemical, Biological, Radiological, and Nuclear Medical Countermeasures.

11 http://www.gpo.gov/fdsys/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf 12 http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf 13 http://www.phe.gov/preparedness/legal/Pages/default.aspx 14 https://www.medicalcountermeasures.gov/federal-initiatives/strategies-and-reports.aspx http://www.gpo.gov/fdsys/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf http://www.phe.gov/preparedness/legal/Pages/default.aspx https://www.medicalcountermeasures.gov/federal-initiatives/strategies-and-reports.aspx https://www.medicalcountermeasures.gov/federal-initiatives/strategies-and-reports.aspx

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Part I: Research and Development Areas of Interest

This section presents an overview of the research and development projects that BARDA seeks to support through this BAA.

Offerors contemplating submitting Quad Charts and White Papers are strongly encouraged to contact BARDA technical POC for the respective area of interest.

Be advised that after a White Paper (or Full Proposal) has been submitted, all communications related to that submission must be through the ASPR’s Office of Acquisitions Management, Contracts, and Grants (AMCG).

Area of Interest #1: CBRN Vaccines

1.1. Anthrax and Smallpox. Submissions for anthrax and smallpox vaccines will not be considered during the open period of this BAA, unless specifically announced through special instructions.

1.2 Sudan ebolavirus and Marburg virus. BARDA is interested in advanced development projects for monovalent vaccines against Sudan ebolavirus and Marburg virus. The proposed vaccine candidate must have demonstrated protection from lethal challenge in non-human primate studies. Preference will be given to candidate products with one or more of the following:

• Phase 1 clinical data

• active Investigational New Drug (IND) with the FDA

• safety toxicity data

• preliminary formulation

• stability indicating assay

• demonstrated small scale manufacturing process

The objective of this program is to advance projects through the end of Phase 2 clinical development. Multivalent candidates will be considered only upon completion of phase 2 clinical study with clear guidance from FDA on regulatory pathway.

1.3 Expansion of availability of licensed anthrax and smallpox vaccines to at risk populations: BARDA is interested in programs to expand availability of licensed anthrax and smallpox vaccines for at risk populations, e.g. pediatric populations.

Interested parties should refer to the Presidential Commission for the Study of Bioethical Issues report “Safeguarding Children: Pediatric Medical Countermeasures”15

1.4 Vaccines against Burkholderia pseudomallei and Burkholderia mallei.

BARDA is interested in advanced development projects for vaccines against B.

pseudomallei and B. mallei. The proposed vaccine candidate must have demonstrated protection from lethal challenge in mouse and non-human primate studies. The following

15 https://www.medicalcountermeasures.gov/BARDA/Documents/PCSBI_Pediatric-MCM508.pdf https://www.medicalcountermeasures.gov/BARDA/Documents/PCSBI_Pediatric-MCM508.pdf

BARDA BAA-18-100-SOL-00003 Amendment 1 Page 16 characteristics provide information regarding BARDA’s preferred profile:

• Vaccines against B. pseudomallei will be acceptable, but those that would target B. mallei in addition are preferred.

• Vaccines showing protection against aerosolized infection, or protection against multiple routes of exposure, are preferred.

• Timeline to Investigational New Drug (IND) submission of less than two years is preferred.

• Vaccines with preliminary formulation ready to be transitioned to GMP manufacturing are preferred.

• Vaccine candidates that offer sterilizing immunity in addition to protection are preferred, but not required.

The objective of this program is to advance projects through the end of Phase 1 clinical development. The following activities are expected to be included:

• Development of any necessary assay(s) for lot release

• Establishment of animal models acceptable to FDA, if necessary

• Development of small scale GMP manufacturing process

• GLP toxicology studies

• Nonhuman primate efficacy studies to include pre-exposure prophylaxis and post-exposure prophylaxis (in conjunction with antibiotic treatment)

• Development and qualification of necessary immunoassays

• Conduct of a Phase 1 clinical trial

Technical Point of Contact: Dr. Eric Espeland; Eric.Espeland@hhs.gov

Contracting Point of Contact: Jonathan Gonzalez; Jonathan.Gonzalez@hhs.gov mailto:Eric.Espeland@hhs.gov mailto:Jonathan.Gonzalez@hhs.gov

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Area of Interest #2: CBRN Antitoxins and Therapeutic Proteins

2.1 Anthrax Antitoxins. Candidates for funding under this BAA must be at TRL-6 or higher and either expand current response capabilities through product type (e.g., peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.).

2.2 Botulism Antitoxins. Candidates for funding under this BAA must either expand current response capabilities through product type (e.g., monoclonal antibodies, peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.). Candidates at TRL-5 or higher are preferred; however, candidates earlier in development may be considered based on the significance of potential improvement upon existing capabilities.

2.3 Smallpox Antiviral. Programs must have evidence of antiviral activity against orthopoxviruses. Programs at higher TRLs (above TRL 5) will be given priority.

2.4 Viral Hemorrhagic Fevers Antiviral. Candidates for funding under this BAA must be at TRL-5 (lead identified) or higher and either expand current response capabilities through product type (e.g., single mAbs, peptides, small molecules or novel compounds), mechanism of action or transformational change in operational use and total life cycle cost (e.g., shelf-life >10 years, significant reduction in cost of goods, etc.).

Technical Point of Contact: Dr. Chia-Wei Tsai; Chia-Wei.Tsai@hhs.gov

Contracting Point of Contact: Erin Greninger; Erin.Greninger@hhs.gov

Area of Interest #3: Antibacterials

In accordance with the Pandemic and All-Hazards Preparedness Act (PAHPA) of 2006 and reauthorized in 2013 (PAHPRA), BARDA has the responsibility to ensure that the United States has a sufficient supply of vaccines and drugs to respond to public health emergencies caused by pandemic influenza, emerging infectious diseases, and chemical, biological, and radiological and nuclear threats. BARDA recognizes the dual utility of antimicrobials for the treatment and prevention of diseases caused by bacterial and viral threat agents and clinically relevant drug resistant pathogens. To achieve its’ national security mission, BARDA seeks to establish public-private partnerships with industry to accelerate the advanced research, clinical development, and regulatory approval of new antibacterial products for the treatment or prevention of infections. Of particular interest to the Government are proposals, which aim to:

3.1 Develop and test antibacterial products that are in development for post-exposure prophylaxis (PEP) and treatment efficacy against one or more of the following biodefense threat agents: Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei. Minimum inhibitory concentration (MIC) data for multiple strains of one or more of these biothreat agents is required; data from non-clinical studies evaluating the antibacterial candidate against any of these biothreat agents in relevant animal models of infection will strengthen a proposal.

mailto:Chia-Wei.Tsai@hhs.gov mailto:Erin.Greninger@hhs.gov

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3.2 Develop new small molecule drugs that treat or prevent resistant bacterial infections either alone or in combination with other therapeutics;

3.3 Develop non-traditional antibacterial therapeutics that treat or prevent resistant infections. Examples include, but are not limited to antibody-based approaches, host-directed therapies including immune modulators, antimicrobial peptides, bacteriophage, microbiome approaches, and inhibitors of quorum sensing or expression of bacterial virulence factors.

Products should also possess activity against one or more of the pathogens categorized by the CDC as an “Urgent” or “Serious” public health threat in the September 2013 CDC Report titled “Antibiotic Resistance Threats in the United States, 2013”. Competitiveness will be enhanced if the proposed candidate possesses activity against Gram negative pathogens.

Under this area of interest, most aspects of drug development are considered permissible including clinical studies, nonclinical studies, safety, toxicology, pharmacokinetics/pharmacodynamics (PK/PD), and microbiological studies, manufacturing, analytical assay development and validation, regulatory submission preparation, and the development and use of diagnostics to enhance clinical trial enrollment.

Qualities that strengthen the competitiveness of a proposal include:

• Candidates demonstrating substantial improvements over existing antimicrobial products are of greatest interest including novel first in class compounds with unprecedented mechanisms of action. If a candidate belongs to an existing class (same/similar chemistry and pathogen target) of antimicrobial products, there must be significant advantages such as overcoming existing resistance mechanisms and/or greatly improved therapeutic properties.

• Greater technological advancement of the candidate: Successive progression through TRLs and corresponding completion of commercial drug development activities will increase the attractiveness of proposals. Data from IND enabling toxicology studies is a requirement improved upon by having filed an IND, and further made attractive with progression into and completion of Phase 1, 2, and 3 clinical studies.

• Regulatory feasibility: Evidence of supportive regulatory correspondences from the FDA concerning the development plan of the candidate will strengthen a proposal submission.

• Special populations: Antimicrobials that offer therapeutic benefit to special populations, particularly pediatric subjects, are an important and underserved area. Proposals that have specific plans and proposed activities to advance a product for approved use in special populations will be viewed more favorably.

• Cost sharing: Proposals that demonstrate a commitment of resources from the Offeror in the form of sharing the cost of the proposed development plan are most advantageous.

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Learn more about Antibacterials16.

Technical Point of Contact: Dr. Christopher Houchens; Christopher.Houchens@hhs.gov

Contracting Point of Contact: Erin Greninger; Erin.Greninger@hhs.gov

Area of Interest #4: Radiological/Nuclear Threat Medical Countermeasures

Injuries resulting from accidental or intentional radiation exposures (from radiological dispersal devices (RDD) or nuclear detonations) are likely to be complex and could include combined injuries from radiation exposure concomitant with mechanical trauma or thermal burns. Radiation causes severe systemic injury at the cellular level including DNA damage and reactive oxygen species production that result in additional cellular physiological etiologies, including cellular apoptosis, loss of progenitor cells, endothelial cell damage, altered metabolism, and induction of inflammatory responses. These systemic injuries lead to the development of infection/sepsis and the clinical manifestations of vascular injury, coagulopathies, ischemia, and resultant multi organ failure.

This area of interest is focused on development of medical countermeasures (MCMs) to treat radiation injury. Programs proposing work in this area of interest should be at a TRL for the radiation, or related, indication of TRL 5 (i.e., completed all activities described for TRL 5); Submissions not meeting the TRL 5 maturity requirement will not be reviewed. Additionally, Offerors should have held a pre-IND meeting with FDA to discuss licensure as an MCM prior to the submission of a White Paper to the BARDA BAA, and should be prepared to provide the minutes from the meeting, if requested.

Development programs should plan to address the needs of at-risk populations.

There are several considerations when proposing a product development program for BARDA Area of Interest 4 – Radiological/Nuclear Threat Medical Countermeasures:

Radiological and Nuclear Strategic Considerations

a) Concept of Operations (CONOPs) for Radiological and Nuclear Incidents

An emergency response to a radiological/nuclear event will likely follow two general phases of treatment: field care and definitive care. The field care treatment phase is generally defined as the first 72 hours of the emergency response, during which time resources and trained personnel are expected to be exceedingly scarce, thus delaying and limiting access to treatment. The definitive care treatment phase extends beyond the initial 72 hours of the emergency response and includes the full range of medical care necessary to manage a patient’s condition, with treatment administered at medical centers and hospitals operating at surge capacity. BARDA priorities include the repurposing of already approved therapies for a new Acute Radiation Syndrome (ARS) indication or advanced development of new therapies. Desirable MCM characteristics to improve flexibility and usability in a mass casualty incident include ease of storage (e.g.

storage at room temperature), favorable deployment and route of administration, and efficacy when administered a minimum of 24 hours or later after a radiation exposure.

Efficacy should be based on improved survival outcome or mitigation of clinical endpoints of radiation injury. Priorities for the definitive care treatment phase could also

16 https://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx https://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx mailto:Christopher.Houchens@hhs.gov mailto:Erin.Greninger@hhs.gov https://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx

BARDA BAA-18-100-SOL-00003 Amendment 1 Page 20 include blood products, cellular therapies and products that enhance the engraftment and/or activity of these therapies.

b) Repurposing Commercially Available Products

BARDA may support evaluation of FDA approved drugs with existing commercial markets for repurposing to expand current indications. For proposed novel products, Offerors should identify a relevant commercial indication and propose activities that offer leveraging opportunities for both the MCM and commercial indication. A clear business strategy should be included in the plan.

c) Addressing Multiple Relevant Indications or Multiple Threat Areas

BARDA prioritizes MCMs that have the potential to treat multiple relevant indications or multiple threat areas (e.g., radiation injury combined with mechanical trauma; radiation and chemical injury).

Radiological and Nuclear Programmatic Priorities

4.1 Advanced Development of MCMs to treat radiation injury due to acute exposure to ionizing radiation. BARDA could support:

a) Evaluation of licensed products for repurposing. Products should have a label indication that could reasonably be expanded to include use in a mass casualty event to treat radiation injury due to acute exposure to ionizing radiation. The proposed development plan could include activities for additional commercially relevant indications.

b) Novel therapeutics to address thrombocytopenia due to acute exposure to ionizing radiation.

c) Novel therapeutics to address systemic injury responses due to acute exposure to ionizing radiation (mechanical trauma can be included as a second indication).

Priority target pathways include coagulopathy, fibrinolysis, vascular injury and sepsis.

Note that the development of field use anti-neutropenics (second generation anti-neutropenics) will not be supported under this funding opportunity.

4.2 Blood Products: Advanced development of next generation blood products that will enhance our ability to respond to mass casualty events and meet blood product treatment gaps. Proposed intended use can be radiation injury, mechanical trauma or both (see considerations above). Potential areas of blood product development include but are not limited to:

a) Development of cell products derived from stem-cells and their progenitors to produce safe and non-alloimmunizing human red blood cell, platelet, or white blood cell products for use in transfusing humans;

b) Technologies for reliably producing hematopoietic stem cells and their progenitors, including optimization of directed differentiation and engraftment of functional and safe hematopoietic cells

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c) Technologies to improve cell processing, optimization of ex vivo expansion, scale up, production, and Good Manufacturing Practice (GMP) manufacturing of human-derived or stem-cell derived blood products.

4.3 Decorporation Agents: Development of decorporation agents, which are either passive (limited generally to the blood pool) or active chelators (preferred; seeks intracellular or distributed depots). BARDA will continue to fund projects to support advanced research and development of Prussian blue formulations appropriate for children under the age of two years.

BARDA encourages innovation. For Area of Interest 4: Radiological/Nuclear, innovations could range from pre-clinical through licensure development plans or strategies. For example, product development plans might include a systems biology approach, blood pharming strategies, or novel regulatory strategies, such as the development of species specific products for approval under the animal rule.

Learn more about Radiological and Nuclear Medical Countermeasures17.

Technical Point of Contact: Dr. Mary J. Homer; Mary.Homer@hhs.gov

Contracting Point of Contact: Jonathan Gonzalez; Jonathan.Gonzalez@hhs.gov

Area of Interest #5: Chemical Threat Medical Countermeasures

Area of Interest #5 includes medical countermeasures (MCMs) that treat the acute health effects of chemical threats, are easy to administer in a mass-casualty situation, and are rapidly effective as post-exposure therapies. The MCMs should be safe and effective for the entire population, including infants, children, adolescents, elderly, pregnant women and immunocompromised individuals. The technical readiness level (TRL) for candidates should be at TRL 4 (i.e. completed all activities described for TRL

4) or higher; in vivo activity and potential for efficacy consistent with the product's intended use as an MCM against a threat agent (i.e.