BAA-18-100-SOL-00003_Amendment_35.pdf

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

BAA-18-100-SOL-00003

Amendment 35 November 15, 2022

Biomedical Advanced Research Development Authority (BARDA)

Contracts Management & Acquisition (CMA)

200 C Street SW

Washington, DC 20201

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 2

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 Antivirals and Antitoxins 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 and Blast 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: [Suspended] MCM Production Platform Systems ... 53 Area of Interest #11 for DRIVe: [Suspended] Solving Sepsis Area of Interest #12 for DRIVe: [Suspended] Early Notification to Act, Control and Treat (ENACT) Area of Interest #13: [Suspended] Advanced Manufacturing Technologies

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 3

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:

K. Executive Order 14042. All applicable contracts and OTAs issued under this BAA must comply with Executive Order 14042, requiring vaccination of individuals receiving USG funding. FAR Clause 52.223-99 is incorporated as a result of EO 14042

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 115

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 4

Attachment 4: Summary of Related Activities

Attachment 5: Quad Chart Format Template

Attachment 6: Government Notice for Handling and Submitting Proposals Attachment 7: Breakdown of Proposed Estimated Cost (Plus Fee) and Labor Hours (For Cost Proposal) Attachment 8: Cost Certification

Attachment 9: Biographical Sketch (NIH, non-fellowship) Attachment 10: BARDA BAA Process Flow Chart Attachment 11: Submission Data Integration Table

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 5

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), Administration for Strategic 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), Administration for Strategic Preparedness and Response (ASPR), Biomedical Advanced Research Development Authority (BARDA)/ Contracts Management & Acquisition (CMA), 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.

This BAA is available on the following websites:

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 6

• MedicalCountermeasures.gov1

• Public Health Emergency - PHE.gov2

• Grants.gov3

• SAM.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 encouraged to submit proposals and to join other entities as team members in

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

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 7 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:

Contracts Management & Acquisition (CMA) 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 Part VIII: 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.

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

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 8 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 and Advanced Innovation Act of 2019.

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.

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 9

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.

The application process is also described in the BARDA BAA Process Flow Chart (Part VIII: Attachment 10) and online on PHE’s BARDA Broad Agency Announcement5.

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 January 31, 2020 April 30, 2020 July 31, 2020 October 31, 2020 January 31, 2021 April 30, 2021 July 31, 2021 October 31, 2021 May 2, 2022 Dec 15, 2022

The final White Paper submission deadline is Dec 15, 2022

A receipt confirmation will be sent within 1 week.

A response will be provided within 120 days of the submission deadline.

5 https://www.phe.gov/about/amcg/BARDA-BAA/Pages/default.aspx https://www.phe.gov/about/amcg/BARDA-BAA/Pages/default.aspx

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 10

Proposal Stage Deadline for Submission* Government Response

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 Dec 15, 2022

A receipt confirmation will be sent within 1 week.

A response will be provided within 120 days of the submission deadline.

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

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 11

Submission Instructions:

All submissions in response to this BARDA BAA must be submitted to the BARDA Digital Resources (BDR) Portal (https://bdr.hhs.gov/) via the process described below.

IMPORTANT: Respondents will be required to apply for a BDR Portal account. This account can be requested by visiting the BDR Portal site and following the applicable prompts.

The account request process is simple but may take several days for approval and access. Account requests will require the Respondent to enter a set of basic information (i.e., first and last name, e-mail address, and phone number). Upon confirmation of a BDR Portal account, the Respondent will login using the prescribed two-factor authentication method. Once login is complete, the Respondent will be prompted to enter information about Respondent’s organization and to input the submission with other project-specific information.

Failure to submit on-time due to late registration will result in the submission not being considered for award.

Respondents will be provided automated confirmation of successful submission.

Prior to submission of a White Paper, 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.

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 mailto:BARDA-BAA@hhs.gov mailto:BARDA-BAA@hhs.gov mailto:BARDA-BAA@hhs.gov

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 12

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 Contracts Management & Acquisition (CMA) 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 website6. Entities with a White 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 Part VIII:

6 https://www.medicalcountermeasures.gov/Request-BARDA-TechWatch-Meeting/ https://www.medicalcountermeasures.gov/Request-BARDA-TechWatch-Meeting/

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 13

Attachment 6 for inclusion requirement of the Government notice.

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 14

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 Administration for Strategic Preparedness and Response (ASPR), in 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- Hazards Preparedness and Advanced Innovation Act of 2019 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 Review7 (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 Influenza8 (August 2010), the BARDA Strategic Plan 2011-20169 (October 2011), and HHS Pandemic Influenza Plan10 (June 2017).

Vaccines, therapeutics, diagnostics, 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 can provide a priming and protective response with a single vaccine dose and are more amenable to

7 https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf 8 https://www.medicalcountermeasures.gov/BARDA/documents/2010%20pcast-influenza-vaccinology.pdf 9 https://www.medicalcountermeasures.gov/media/745/bardastrategicplan9-28--508.pdf 10 https://www.medicalcountermeasures.gov/BARDA/Documents/pan-flu-report-2017v2.pdf https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf https://www.medicalcountermeasures.gov/media/1138/mcmreviewfinalcover-508.pdf https://obamawhitehouse.archives.gov/sites/default/files/microsites/ostp/PCAST-Influenza-Vaccinology-Report.pdf https://obamawhitehouse.archives.gov/sites/default/files/microsites/ostp/PCAST-Influenza-Vaccinology-Report.pdf https://www.medicalcountermeasures.gov/media/745/bardastrategicplan9-28--508.pdf https://www.medicalcountermeasures.gov/BARDA/Documents/pan-flu-report-2017v2.pdf

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 15 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 older adults, 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 2017-2018 PHEMCE Strategy and Implementation Plan11. 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, older adults, 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 sets in an easily understandable format to support the breadth of BARDA’s MCM

11 https://www.medicalcountermeasures.gov/BARDA/documents/2017-phemce-sip.pdf https://www.medicalcountermeasures.gov/BARDA/documents/2017-phemce-sip.pdf

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 16 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 Act12 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.

113-513, (PAHPRA).

• The Pandemic and All-Hazards Preparedness and Advanced Innovation Act of 201914 Public Law 116-22 and 42 USC247d-7e15; (PAHPAIA)

Learn more about legal authorities, policies, and committees16 and strategies and reports17 for pandemic influenza, Chemical, Biological, Radiological, and Nuclear Medical Countermeasures.

12 https://www.govinfo.gov/content/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf 13 https://www.govinfo.gov/content/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf 14 https://www.congress.gov/bill/116th-congress/senate-bill/1379 15 https://uscode.house.gov/view.xhtml?req=42+USC+247d-7e 16 http://www.phe.gov/preparedness/legal/Pages/default.aspx 17 https://www.medicalcountermeasures.gov/federal-initiatives/strategies-and-reports.aspx https://www.govinfo.gov/content/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf https://www.govinfo.gov/content/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf https://www.govinfo.gov/content/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf https://www.congress.gov/bill/116th-congress/senate-bill/1379 https://www.congress.gov/bill/116th-congress/senate-bill/1379 https://uscode.house.gov/view.xhtml?req=42+USC+247d-7e 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

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 17

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/BARDA’s Contracts Management & Acquisition (CMA).

The final white paper submission deadline is Dec 15, 2022. The final full proposal submission deadline is Dec 15, 2022 or as specified in the invitation letter.

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 18

Area of Interest #1: CBRN Vaccines

The mission of BARDA’s CBRN Vaccine program includes a critical need to develop vaccines to prevent the spread of disease or potentially protect those individuals who may be or who have recently been exposed to a threat agent but are not yet symptomatic. The CBRN Vaccine program seeks to support new vaccines or technologies that can provide flexible approaches to address emerging threats, improve operational logistics, and increase the sustainability of preparedness strategies.

Vaccine(s) will be critical to mount an appropriate response to the emergence or spread of a pathogen that poses a significant threat to national security or public health. The current area of interest will focus on Ebola viruses, Marburg virus.

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 Ebola and Marburg virus. BARDA is interested in advanced development projects for monovalent vaccines against Sudan ebolavirus and Marburg virus, as these viruses represent urgent, unmet needs in terms of vaccine preparedness. The proposed vaccine candidate must have demonstrated protection from lethal challenge in non-human primate studies. The suggested animal model will utilize an acceptable intramuscular challenge model, with the Gulu strain (for Sudan ebolavirus) and/or the Angola strain (for Marburg virus). While not required, preference will be given to candidate products with Phase 1 clinical data, an active Investigational New Drug (IND) with the FDA, safety toxicity data, and demonstrated manufacturing process to support use in clinical trials. The objective of this program is to advance projects through the end of Phase 2 clinical development. The scope of work may include late preclinical development as long as IND submission is expected within one year of submission.

Multivalent candidates will be considered only upon completion of phase 2 clinical study with clear guidance from FDA on regulatory pathway.

Alternative administration approaches and technologies that may reduce or eliminate bottlenecks related to ancillary supplies and distribution are of high interest. In the case of Sudan and Marburg vaccines, any such approaches should be evaluated early in the development program. For example, approaches that may be amenable to administration of the vaccine without needles, or distributed manufacturing of the vaccine, would potentially reduce bottlenecks related to syringe and needle availability and manufacturing scale up.

BARDA is interested in advanced development projects for licensed vaccines against Zaire ebolavirus that may meet key program goals in terms of improving the operational use of late-stage products. BARDA’s goals in this area are focused on 1) expanding label indication to include special populations and/or 2) generating data to support a potential boosting strategy, if needed. Projects in this area will be limited to vaccine candidates for which phase 2 clinical trials have been completed.

Technical Point of Contact: Daniel Wolfe; Daniel.Wolfe2@hhs.gov

Contracting Point of Contact: BARDA-BAA@hhs.gov with the subject line “Contracting questions: AOI 1 (CBRN Vaccine): <brief description>” mailto:Daniel.Wolfe2@hhs.gov mailto:BARDA-BAA@hhs.gov?subject=Contracting%20questions:%20AOI%201%20(CBRN%20Vaccines):%20%3cbrief%20description%3e

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 19

Area of Interest #2: CBRN Antivirals and Antitoxins

BARDA is seeking therapeutics that will improve preparedness and response against toxins and viruses that pose a threat to the American public. Candidates must demonstrate efficacy against anthrax, botulism, smallpox or filoviruses as summarized in 2.1-2.4. BARDA is also interested in such candidates that have potential for broad activity against multiple toxins, toxin classes, viruses, virus genera or virus families.

BARDA’s strategy is to develop products that are sustainable, improve operational logistics or capabilities, and reduce risk through diversification of countermeasures.

Candidates for funding under this area should be at TRL-5 (lead identified) or higher, as indicated below. However, candidates earlier in development may be considered if it is anticipated they will significantly improve existing capabilities. Competitive products will expand current response capabilities either through:

1. Product type (e.g., mAbs or mAb cocktails, peptides, small molecules or novel compounds, etc.)

2. Mechanism of action

3. A significant change in operational use and/or total life cycle cost (e.g., route of administration, shelf-life >10 years, significant reduction in cost of goods, etc.)

Additional considerations for Offerors preparing white papers or full proposals can be found in Part II: Development and Technical Objectives of this BAA.

2.1 Anthrax Antitoxins. Candidates for funding under this BAA must advance or expand current response capabilities against the threat of inhalational anthrax. The Department of Homeland Security issued Material Threat Determinations for Bacillus anthracis (B. anthracis) in 2004 and multi-drug resistant (MDR) B. anthracis in 2006. B.

anthracis is considered a serious bioterrorism agent due to the ability of the spores to persist in the environment, the ability of aerosolized spores to readily cause infection, and the high mortality of inhalation anthrax.

HHS is pursuing a comprehensive strategy to address the threat of anthrax, including the procurement of antimicrobial drugs, vaccines, and therapeutics to the Strategic National Stockpile. A competitive product will encompass some or all of the characteristics below to maximize and diversify the capabilities of the United States Government to launch an effective response to a public health emergency caused by anthrax:

• Non-intravenous route of delivery;

• A minimum of three-year shelf life with the potential for extension to 10-years;

• Product form not requiring cold-chain;

• Equivalent or improved efficacy in comparison to currently licensed products;

• Different product class and/or mechanism of action relative to FDA-approved anthrax antitoxins;

• Compatibility with, and mechanism of action that complements, antibiotic treatment;

• Potential for efficacy against toxins produced by MDR or engineered B.

anthracis.

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 20

2.2 Botulism Antitoxins. Candidates for funding under this BAA must advance or expand current response capabilities against the threat of botulinum intoxication. In 2004, the Department of Homeland Security (DHS) determined that Clostridium botulinum (C. botulinum) presents a material threat to national security. Based on this Material Threat Determination and the subsequent Material Threat Assessment, HHS has identified a requirement for a botulinum antitoxin with efficacy against botulinum neurotoxin serotypes A-G.

To improve upon and diversify the United States Government’s preparedness against this priority threat, BARDA aims to support the development of improved next-generation botulism antitoxins. A competitive antitoxin product will encompass some or all of the characteristics below to maximize and diversify the capabilities of the United States Government to launch an effective response to a public health emergency caused by botulinum:

• A single heptavalent product or a combination of antitoxins that covers serotypes A-G;

• Non-intravenous route of delivery;

• A minimum of three-year shelf life with the potential for extension to 10-years;

• Product form not requiring cold-chain;

• Equivalent or improved efficacy in comparison to currently licensed products;

• Different product class and/or mechanism of action relative to FDA-approved botulinum antitoxins.

2.3 Smallpox Antiviral. The Department of Homeland Security (DHS) issued a Material Threat Determination for smallpox in 2004, establishing it as a threat to national security. Periodic smallpox outbreaks were common prior to the twentieth century with fatality rates of greater than thirty percent. Although smallpox was eliminated as an endemic disease by 1980, the potential re-emergence of the virus via natural sources or a bioterrorist act remain a possibility.

A competitive therapeutic candidate will encompass the characteristics below to build upon existing capabilities of the United States Government:

• TRL-6 or higher;

• Demonstrated preclinical efficacy against orthopoxviruses in appropriate animal models;

• Different product class and/or mechanism of action relative to existing FDA-approved smallpox therapeutics;

• Potential to complement existing FDA-approved smallpox therapeutics;

• Offers potential for a substantial improvement in or expansion of current response capabilities; products that offer minimal or incremental gains are not a current priority.

2.4 Filovirus Therapeutics. In 2006, the Department of Homeland Security determined that Ebola virus and Marburg virus are material threats to national health security. Medical countermeasures that can be deployed in the event of a filovirus outbreak are a crucial component to the United States Government’s outbreak response plan. BARDA is seeking to augment response capabilities with therapeutics targeting species of Ebolavirus and Marburgvirus with potential to cause disease in humans.

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 21

A competitive therapeutic candidate will encompass some or all of the characteristics below to build upon existing capabilities of the United States Government:

• Demonstrated preclinical efficacy for at least one filovirus species in a relevant animal model, with strong preference for efficacy when administered after onset of symptoms and for demonstrated or anticipated efficacy against multiple filovirus species;

• A minimum of three-year shelf life with the potential for extension to 10-years;

• Product form not requiring cold-chain;

• Non-intravenous route of delivery;

• A product type other than a monoclonal antibody or antibody cocktail.

Specifically for candidate products with preclinical efficacy only for the Zaire ebolavirus, candidates must be TRL-6 or higher and have at least one of the following:

• Non-intravenous route of delivery;

• Different product class and/or mechanism of action relative to existing FDA-approved Ebola virus therapeutics;

• Potential to complement existing FDA-approved Ebola virus therapeutics via demonstrable efficacy in immune privileged sites, including the reproductive tract and central nervous system; efficacy against persistent infection; beneficial impact on long term sequelae associated with Ebola virus infection; or efficacy in severe acute infection.

Technical Point of Contact: Dr. Karen Martins; Karen.Martins@hhs.gov questions: AOI 2 (CBRN Antitoxin): <brief description>” mailto:Karen.Martins@hhs.gov mailto:BARDA-BAA@hhs.gov?subject=Contracting%20questions:%20AOI%202%20(CBRN%20Antitoxin):%20%3cbrief%20description%3e

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 22

Area of Interest #3: Antibacterials

The mission of BARDA’s Antibacterials Program is to minimize the morbidity and mortality caused by multidrug-resistant organisms (MDROs) and biothreat pathogens.

Critical to national preparedness is the availability of safe and effective antimicrobial drugs for all patient populations. During routine medical practice, public health emergencies, and mass casualty events, hospital-associated and community-acquired infections caused by MDROs can complicate patient care and recovery. Antimicrobial resistance also poses a risk to our ability to respond to biothreat infections due to limited treatment options, particularly for special populations including pediatrics. Antimicrobial resistance places a substantial health and economic burden on society and will continue to do so if not adequately addressed.

The Antibacterials Program seeks to accelerate innovation and product development through public-private partnerships that support the advanced research, development, manufacture, regulatory approval, and availability of novel antimicrobial candidates against MDROs. Of particular interest to the Government are proposals which aim to:

3.1 Develop products for treatment of MDROs and biothreat pathogens.

Drug candidates with activity against bacterial pathogens identified by the Centers for Disease Control and Prevention (CDC) as “urgent” or “serious” threats18 as well as multiple strains of one or more biothreat pathogens (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei) will be prioritized. Though candidates with aforementioned dual activity are favored, candidates with activity only against CDC priority bacterial pathogens (no biothreat activity) will also be considered.

Priority will also be given to drug candidates that:

1. Address hospital-associated and community-acquired drug-resistant infections as well as secondary or opportunistic infections;

2. Are clinically differentiated from approved antimicrobials (e.g. respiratory or bloodstream infections);

3. Have an improved formulation or alternate delivery regimen (e.g. oral, once daily intravenous or intramuscular dose);

4. Offer therapeutic benefit to all segments of the American population, including but not limited to pediatric subjects, older adults, and pregnant women.

5. Have an activity profile (MIC50 and MIC90) and propose a development path that will generate data that could support a pre-Emergency Use Authorization for a biothreat pathogen (e.g. animal efficacy studies and potentially a clinical trial for respiratory infections);

All aspects of advanced clinical stage drug development are considered permissible for funding, including nonclinical studies, safety, toxicology, microbiological studies, pharmacokinetics (PK)/pharmacodynamics (PD), manufacturing, analytical assay development and validation, clinical studies including pediatric studies, regulatory submission preparation, development of diagnostics to enhance clinical trial enrollment or inform product use in the target patient population (e.g. susceptibility testing or

18 https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

BARDA BAA-18-100-SOL-00003 Amendment 35 Page 23 therapeutic drug monitoring), and post-approval requirements.

3.2 Treatment of MDR fungal infections.

BARDA is seeking to support the development of broad-spectrum antifungal drug candidates with novel mechanisms of action that target Candida species, including Candida auris, and Aspergillus species. Candidates that also demonstrate activity against rare molds, such as Mucorales, are of interest. Drug candidates must be TRL6 or higher.

Priority will be given to drug candidates with the following characteristics:

• Represent a first-in-class antifungal with a novel mechanism of action (including novel targets). Candidates within existing classes (e.g., azoles, echinocandins, polyenes, pyrimidines) may be considered though they must demonstrate a significant improvement over FDA approved products (e.g., reduced toxicity, effectiveness against resistant strains, acceptable dosing schedule, expanded spectrum of activity, potential for use in pediatrics or other special populations);

• Have an improved formulation or alternate delivery regimen (e.g., oral and intravenous) with limited duration of therapy

Qualities that strengthen the competitiveness of a proposal

A well-conceived proposal should summarize key concepts that demonstrate the product developer’s knowledge and…