rev5_BAA_BAA-16-100-SOL-00001_CBRN_20160210.pdf

Broad Agency Announcement (BAA) for the Advanced Research and Development of Chemical, Biological, Radiological, and Nuclear (CBRN) Medical Countermeasures for BARDA

BAA-16-100-SOL-00001

(Amendment 5 dated February 10, 2017, all changes highlighted in Yellow)

Biomedical Advanced Research and Development Authority

(BARDA)

330 Independence Avenue, SW, Room G644

Washington, DC 20201

BARDA BAA-16-100-SOL-00001 (CBRN) Page 2

Table of Contents

Broad Agency Announcement (BAA) for the Advanced Research and Chemical, Biological, Radiological, and Nuclear (CBRN) Medical Countermeasures for BARDA

INTRODUCTION

OVERVIEW INFORMATION

Agency Name:

Issuing Office:

Research Opportunity Title:

Announcement Type and Date:

Eligible Offerors:

Research Opportunity Description:

Technological Maturity:

Number of Awards:

Type of Award:

Application Process:

Submission Deadlines and Government Response Time(s):

Contact/Submission Information:

Preliminary Inquiries:

TechWatch Program:

Special Instructions:

Proposal Handling and Submission Information:

BACKGROUND

Part I: Research Areas of Interest

Area of Interest #1: Vaccines Area of Interest #2: Antitoxins and Therapeutic Proteins

Area of Interest #3: Antimicrobial Therapeutics Area of Interest #4: Radiological/Nuclear Threat Medical Countermeasures Area of Interest #5: Chemical Threat Medical Countermeasures

Area of Interest #6: Clinical Diagnostics Part II: Research and Technical Objectives Part III: Reporting Requirements and Deliverables

Reports:

Meetings:

Regulatory and Quality Management:

Audits / Site Visits:

Program Management Plans and Documentation:

Earned Value Management:

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

B. Security Plan:

C. Identification and Disposition of Data:

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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)

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 and Full Proposal Evaluation Criteria B. Other Evaluation Factors and Considerations

C. Evaluation Rating D. Additional Information

Part VIII: Attachments

Attachment 1: Technology Readiness Level Criteria Attachment 2: Target Product Profile Template

Attachment 3: Regulatory Guidance for Devices

Attachment 4: Summary of Related Activities

Attachment 5: Quad Chart Format Template Attachment 6: Government Notice for Handling & Submitting Proposals 87 Attachment 7: Breakdown of Proposed Estimated Cost (Plus Fee) and Labor Hours (For Cost Proposal) Attachment 8: Total Life Cycle Costs (TLCC) Definition

Attachment 9: Additional Requirements Information

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INTRODUCTION

This Broad Agency Announcement (BAA), which sets forth research areas of interest for the 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 "The Competition in Contracting Act of 1984" 41 U.S.C. § 251 et seq. A formal Request for Proposal and/or additional information regarding this announcement will not be issued. Paper copies of this announcement will not be issued. The 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 BARDA 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 Federal Acquisition Regulation.

OVERVIEW INFORMATION

Agency Name:

Department of Health and Human Services, Office of the Secretary, Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority 330 Independence Avenue, SW, RM G644, Washington, DC, 20201

Issuing Office:

Department of Health and Human Services, Office of the Secretary, Assistant Secretary for Preparedness and Response, Acquisition Management, Contracts & Grants (AMCG), 330 Independence Avenue, SW, RM G644, Washington, DC, 20201

Research Opportunity Title:

BARDA Broad Agency Announcement for the Advanced Research and Development of Chemical, Biological, Radiological, and Nuclear (CBRN)

Announcement Type and Date:

Broad Agency Announcement renewal announcement, October 1, 2015 as: BAA-16-

100-SOL-00001

Note: This Broad Agency Announcement is a re-issuance of the following versions which have been re-issued annually:

Initial Announcement as BARDA CBRN BAA-09-34, issued March 4, 2009 Renewed March 4, 2010 as BARDA CBRN BAA-10-100-SOL-00012 Renewed March 4, 2011 as BARDA CBRN BAA-11-100-SOL-00009 Renewed June 8, 2012 as BARDA CBRN BAA-

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12-100-SOL-00011. Renewed July 31, 2013 as BARDA CBRN BAA-13-100-SOL-00013.

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 periodically check these websites 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 also 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 prime 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 fully 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 https://www.fbo.gov/ https://www.medicalcountermeasures.gov/ http://www.phe.gov/ http://www.grants.gov/ https://www.fbo.gov/ https://www.medicalcountermeasures.gov/ http://www.phe.gov/ http://www.grants.gov/

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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 submitting proposals.

In accordance with federal statutes, regulations, and 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 Opportunity Description:

The Biomedical Advanced Research and Development Authority solicits the advanced research and development of medical countermeasures for chemical, biological, radiological, and nuclear agents that threaten the U.S. civilian population. BARDA anticipates that research and development activities awarded under this BAA will serve to advance candidate medical countermeasures towards FDA licensure/approval and consideration for acquisition.

The purpose of this BAA is to solicit proposals that focus on one or more of the following solicited areas of interest as listed here and further described in Part I of this announcement.

Research Areas of Interest:

1. Vaccines

2. Antitoxins and Therapeutics Proteins

3. Antimicrobial Therapeutics

4. Radiological / Nuclear Threat Medical Countermeasures

5. Chemical Threat Medical Countermeasures

6. Clinical Diagnostics

Research and technical objectives are described in Part II and efforts proposed by Offerors may include activities in Non-Clinical Research and Development, Process Development, Formulation, and Manufacturing Development, 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 level identified should meet or exceed the requirements of the given Research Area of Interest. Each White Paper should also contain sufficient supporting information to justify the TRL rating. Criteria for determining the appropriate TRL level for a product can be found in Attachment 1. Note that all activities within a TRL level (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 drugs and biologics (Attachment 1B).

Number of Awards:

Multiple awards of various values are anticipated and are dependent upon the program

BARDA BAA-16-100-SOL-00001 (CBRN) Page 7 priorities, proposals’ scientific/technical merits, how well the proposals fit BARDA’s areas of interest, and available funding. Anticipated funding for the program (not per contract or award) may range from $2M to $415M dollars subject to congressional appropriations. This funding profile is an estimate only and will not be a contractual obligation for funding. All funding is subject to change due to government discretion and funding availability.

Type of Award:

A contract awarded under this BAA may utilize: Cost-Reimbursement, Cost-plus-fixed-fee (CPFF), Cost-plus-incentive-fee (CPIF), Firm fixed price (FFP), a cost sharing structure. Although cost sharing is not required under this BAA; however, formal or informal cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

If the government contemplates the award of a cost 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.

BARDA 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. 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.

Offerors whose Quad Chart and White Paper receive a favorable evaluation will be invited by e-mail to submit a Full Proposal. Offerors whose Quad Chart and White Paper did not receive a favorable evaluation will be notified by 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 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.

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Submission Deadlines and Government Response Time(s):

Table 1: Submission Deadlines and Government Response Time

Proposal Stage Deadline for Submission* USG Response

Stage 1: Quad Chart and White Paper

Areas 1, 2,3, 6:

30-Jan-2016 30-Apr-2016 30-Jul-2016 30-Oct-2016 30-Jan-2017 30-Apr-2017 30-Jul-2017 31-Oct-2017

Areas 4,5:

Open for continuous submission, subject to the BAA expiration date.

The final White Paper deadline is October 31, 2017.

Areas 1, 2, 3, 6: Invitation letters sent 90 days from submission of the next interim or final deadline following White Paper submission

Areas 4, 5:

Invitation letters sent 90 days from submission.

Stage 2: Full Proposal As specified in the invitation Letter

As specified in the invitation letter

Source Selection Notification (pending availability of funds)

Decision within 180 calendar days of receipt of Full Proposal or final revised proposal.

*Submissions are due each date at 4:30PM EST. Receipts for all White Papers submitted will be sent electronically within one (1) week of submission.

Contact/Submission Information:

All submissions and administrative inquiries regarding this BAA shall be addressed to CBRN-BAA@hhs.gov.

Technical questions should be directed to the Technical Point of Contacts (POCs) shown following each research areas of interest. These POC’s are located, in “Part I:

Research Areas of Interest.” When an inquiry is made, please include all pertinent contact information.

Be advised that after a white paper (or full proposal) has been submitted, all communications related to that submission must be through the BARDA mailto:CBRN-BAA@hhs.gov.

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Contracting Office AMCG.

As a white paper is not considered a “proposal,” no debriefing will be provided defined by FAR Subpart 15.5.

Quad Chart and White Papers WILL NOT BE ACCEPTED after 4:30 PM (Eastern Standard Time) on 31 October 2017. The submission deadlines are listed below.

Preliminary Inquiries:

BARDA 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 development proposals to make preliminary inquiries as to the general need for the type of development effort contemplated before expending extensive effort in preparing a detailed development proposal or submitting proprietary information.

Offerors contemplating submitting Quad Charts, White Papers, and Full Proposals are strongly encouraged to contact the appropriate technical Point of Contact (POC) at BARDA (see names and e-mail addresses listed immediately after each research area of interest). Offerors are advised that only a Contracting Officer may obligate the Government to any agreement involving expenditure of Government funds.

TechWatch Program:

Offerors under this BAA are invited to arrange a meeting at BARDA headquarters through the TechWatch program. 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 AMCG contract 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 arrange a TechWatch meeting and for more information about the TechWatch program, offerors should visit the TechWatch website5.

Please allow sufficient time for BARDA to schedule a meeting with your organization.

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 are tailored to a specific area of interest and may have a unique submittal date. The information requested in these instructions should be used along with Part VI of the BAA to format and prepare the Technical and Cost Proposals.

Offerors should follow the instructions in Part VI of the BAA, and include the information requested therein.

Proposal Handling and Submission Information:

https://www.medicalcountermeasures.gov/barda/advancing-innovation/techwatch.aspx https://www.medicalcountermeasures.gov/barda/advancing-innovation/techwatch.aspx

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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 by FAR 52.215- 1(e) “Restrictions on disclosure and use of data,” and outlined in the Attachments to this BAA.

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 absolutely 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.

BACKGROUND

BARDA, the lead federal agency for supporting advanced development of medical countermeasures (MCM) to address CBRN threats for the civilian population, is located within the Office of the Assistant Secretary for Preparedness and Response (ASPR), U.S. Department of Health and Human Services (HHS). BARDA is soliciting proposals for the advanced research and development of MCM for chemical, biological, radiological, and nuclear (CBRN) agents that threaten the U.S. civilian population. The continuing threat of terrorism underscores the compelling need to develop new and improved MCM for protecting all segments of the 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). Contracts resulting from this BAA may also benefit from multiple core services that BARDA provides already, 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.

BARDA’s priorities are aligned with the preparedness mission of the HHS Public Health

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Emergency Medical Countermeasures Enterprise (PHEMCE), as articulated in the 2012 PHEMCE Strategy and Implementation Plan6. Specifically, HHS has generally adopted a strategy of developing and acquiring medical countermeasures 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 medical countermeasures 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/development and acquisition of MCM such as vaccines, therapeutics, and diagnostics.

BARDA strives to drive innovation in support of the underlying capabilities necessary to develop and manufacture medical countermeasures that align with the BARDA mission and PHEMCE goals. As such, BARDA is interested in the implementation of Continuous Manufacturing (CM) processes for advanced development of therapeutics. CM is the integration of multiple unit operations into a single end-to-end system based on model control that allows for constant reagent influx and respective outflow of product.

Although CM is not required for successful proposal submission, BARDA is particularly interested in CM development and use for existing BARDA funded products and new potential product candidates where there can be a measurable impact on efficiencies compared to traditional batch manufacturing. This may include, but are not limited to, improvements in rate and yield of production, reagent usage, process steps, facility footprint and economic return. Potential offerors are encouraged to consider incorporating aspects of CM into their product development plan. Proposals may include CM technology development or improvements as well as preliminary steps to evaluate the feasibility of CM as compared to traditional batch processes.

For additional requirements information:

The Pandemic and All Hazard Preparedness Act7 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.

113-58, (PAHPRA) authorizes BARDA to (i) conduct ongoing searches for, and support calls for, potential qualified countermeasures and qualified pandemic or epidemic products; (ii) direct and coordinate the countermeasure and product advanced research and development activities of the Department of Health and https://www.medicalcountermeasures.gov/media/13962/2012-phemce-implementation-plan.pdf http://www.gpo.gov/fdsys/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf https://www.medicalcountermeasures.gov/media/13962/2012-phemce-implementation-plan.pdf https://www.medicalcountermeasures.gov/media/13962/2012-phemce-implementation-plan.pdf 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

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Human Services; (iii) establish strategic initiatives to accelerate countermeasure and product advanced research and development (which may include advanced research and development for purposes of fulfilling requirements under the Federal Food, Drug, and Cosmetic Act or section 351 of this Act) and innovation in such areas as the Secretary may identify as priority unmet need areas; and (iv) award contracts, grants, cooperative agreements, and enter into other transactions, for countermeasure and product advanced research and development.

Learn more about legal authorities, policies, and committees9 and strategies and reports10 for Chemical, Biological, Radiological, and Nuclear Medical Countermeasures.

http://www.phe.gov/preparedness/legal/Pages/default.aspx https://www.medicalcountermeasures.gov/federal-initiatives/strategies-and-reports.aspx 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 Areas of Interest

This section presents an overview of the CBRN-related research and development projects that BARDA seeks to support through this BAA. Each Offeror should also review Part II: Technical Objectives.

Offerors contemplating submitting quad charts and white papers are strongly encouraged to contact BARDA technical point of contact 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: Vaccines

1.1 Advanced development projects for next generation anthrax vaccines that provide significant advantages over the currently licensed Anthrax Vaccine Absorbed (AVA), including one or more of the following:

Fewer doses to protection

Faster protective immune response

Improved storage conditions (e.g. no cold chain)

The proposed vaccine candidate (final formulation) must have 12 months of stability data as measured by acceptable stability indication assay. Preference will be given to candidate products where the final vaccine formulation has demonstrated comparability, non-inferiority preferred, to the current licensed anthrax vaccine in a non-clinical, lethal challenge study as measured by survival and immunological response by toxin Neutralization Assay (TNA). The study to show comparability or non-inferiority will be in a single, well designed study. Preference also will be given to vaccine candidate (final formulation) with an active IND and human safety data at time of submission.

1.2 Advanced development projects for vaccines against Ebola and Marburg viral hemorrhagic fevers. The proposed vaccine candidate must have demonstrated protection from lethal challenge in non-clinical animal studies, with preference given to candidate products with data from non-human primate studies. Preference will also be given to candidate products with one or more of the following:

multivalent vaccine 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. Offerors are encouraged to meet with BARDA through the TechWatch

BARDA BAA-16-100-SOL-00001 (CBRN) Page 14 mechanism prior to submitting a white paper. Learn more about requesting a TechWatch meeting11.

1.3 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 on Safeguarding Children: Pediatric Medical Countermeasures Research12 report.

1.4 Submissions for smallpox vaccines will not be considered during the open period of this BAA, unless specifically announced through special instructions.

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

Area of Interest #2: Antitoxins and Therapeutic Proteins

2.1 Development of peptide or small molecule antitoxins, and other novel compounds, with innovative formulations offering enhanced long-term stability.

The candidate must be at TRL-6 (active IND and human safety data).

2.2 Development of antibody treatments and other therapeutic agents for viral hemorrhagic fevers viruses. Programs must be at TRL-5 with a lead candidate identified.

Technical Point of Contact: Dr. Chia-Wei Tsai chia-wei.tsai@hhs.gov

Area of Interest #3: Antimicrobial Therapeutics

In accordance with the Pandemic and All-Hazards Preparedness Act (PAHPA) of 2006 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 emerging and drug resistant pathogens.

Moreover, in accordance with the National Strategy for Combating Antibiotic-Resistant Bacteria and the Executive Order on Combating Antibiotic Resistant Bacteria, BARDA aims to form public-private partnerships to accelerate research and development of new antimicrobial therapeutics 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 advanced development for post-exposure prophylaxis (PEP) and treatment efficacy against one or more biodefense threat agents (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei). Minimum inhibitory concentration (MIC) data for multiple strains of each threat agent bacterial species under consideration is required;

larger data sets (e.g. MIC90 calculations) will strengthen the proposal.

3.2 Develop new small molecule drugs that treat or prevent resistant microbial infections either alone or in combination with another therapeutic;

https://www.medicalcountermeasures.gov/Request-Meeting.aspx http://bioethics.gov/sites/default/files/PCSBI_Pediatric-MCM508.pdf https://www.medicalcountermeasures.gov/Request-Meeting.aspx https://www.medicalcountermeasures.gov/Request-Meeting.aspx http://bioethics.gov/sites/default/files/PCSBI_Pediatric-MCM508.pdf http://bioethics.gov/sites/default/files/PCSBI_Pediatric-MCM508.pdf mailto:eric.espeland@hhs.gov mailto:chia-wei.tsai@hhs.gov

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3.3 Develop non-traditional antibacterial therapeutics that treat or prevent resistant infections either alone or in combination with another therapeutic. Examples include, but may not be limited to, antibody-based approaches, host-directed therapies including immunomodulators, antimicrobial peptides, phage, microbiome approaches; and approaches to inhibit quorum sensing and expression of bacterial virulence factors.

Products should possess activity against one or more of the pathogens categorized as serious, urgent, or concerning threats in the September 2013 CDC Report titled Antibiotic Resistance Threats in the United States, 2013. Competitiveness will be enhanced if the proposed product(s) possess activity against Gram negative pathogens.

Products may also be assessed for the treatment or prevention of biothreat agent infection.

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

Qualities that strengthen the competitiveness of a proposal include:

Substantial improvements over existing antimicrobial products, novel first in class compounds with unprecedented robust mechanisms of action are urgently needed. If a compound belonging to an existing class (same/similar chemistry and pathogen target) of antimicrobial products is proposed, there must be significant advantages such as overcoming existing resistance mechanisms and/or greatly improved therapeutic properties.

Greater technological advancement of the lead compound: Successive progression through TRL levels 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 responses from the FDA concerning the development plan of the drug will reduce risk to a potential investment by BARDA.

Special populations: Antimicrobials that offer therapeutic benefit to special populations, particularly pediatric subjects, are an important and underserved area. Proposals that have specific plans, likely utility, 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 Broad Spectrum Antimicrobial13.

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

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

Concept of Operations (CONOPs) for Radiological and Nuclear Incidents

The current thinking for an emergency response to a radiological/nuclear event suggests two general phases of treatment:

a. Field Care: This treatment phase is generally defined as the first 72 hours of the emergency response. The primary goal is to provide life-saving interventions and immediate care where necessary. Treatment will likely be administered at or near the incident site or at peripheral assembly sites for evacuation. Resources and trained personnel are expected to be exceedingly scarce. MCMs should be compatible with the published RTR medical response system (Prehosp Disaster Med. 2009 May-Jun; 24(3):167-78).

Emphasis is placed on the following MCM qualities:

o Ease of administration o High therapeutic index o Robust storage, ease of deployment

The current area of interest scope does not currently include the development of field use anti-neutropenics.

b. Definitive Care: This treatment phase extends beyond the initial 72 hours of the emergency response. The primary goal is to fully manage a patient’s condition.

This includes the full range of preventive, curative, acute, convalescent, restorative, rehabilitative and palliative medical care. Treatment will primarily be administered at medical centers and hospitals operating at surge capacity.

Though resources and trained personnel are expected to be strained, their scarcity will not be as severe as that of the Field Care phase.

BARDA’s interest is in the development of specific medical countermeasures to mitigate or treat sub-syndromes of Acute Radiation Syndrome (ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE), blood products, and treatments for severe thermal burns. The list does NOT reflect prioritization.

Radiological and Nuclear Programmatic Priorities

Based on the near-, mid-, and long-term objectives for radiological and nuclear threats prescribed by the 2014 Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Strategy and Implementation Plan14 (p. 80-81), BARDA is interested in the following programmatic areas for Area of Interest #4:

https://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf https://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx mailto:christopher.houchens@hhs.gov http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf

BARDA BAA-16-100-SOL-00001 (CBRN) Page 17

4.0 Acute Radiation Syndrome (ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE): “BARDA will support evaluation of a number of commercial drugs for repurposing to enable use in the treatment of exposure to radiological and nuclear agents, ensuring that at-risk population needs are considered.

BARDA will also support the advanced research and development of novel compounds for PEP (post-exposure prophylaxis) and treatment of exposure to radiological and nuclear threats.

4.1 Development of mitigators or treatments for subsyndromes associated with Acute Radiation Syndrome (ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE), arising from exposure to ionizing radiation. The subsyndromes of current interest to BARDA are the thrombocytopenia component of the hematopoietic subsyndrome and the gastrointestinal subsyndrome. Proposals that address these areas will be given higher priority over proposals addressing other subsyndromes.

Additionally, proposed MCMs that target underlying pathophysiological endpoints with a clear etiology to the prioritized subsyndromes are also of interest. The technical readiness level for candidates should be at TRL 5 or higher for an ARS or DEARE indication (i.e., completed all activities described for TRL 5); 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. Treatments that have efficacy when administered 24 hours or more post irradiation are of particular interest. For clarity, ALL of the following activities should be completed prior to submission: Assays: Initiate development of in-process assays and analytical methods for product characterization and release, including assessments of potency, purity, identity, strength, sterility, and quality as appropriate;

Manufacturing: Initiate process development for small-scale manufacturing amenable to GMP; Target Product Profile: Draft preliminary Target Product Profile. Shelf life, storage conditions, and packaging should be considered to ensure that anticipated use of the product is consistent with the intended use for which approval will be sought from FDA;

TRL 5A: Demonstrate acceptable Absorption, Distribution, Metabolism and Elimination characteristics and/or immune responses in non-GLP animal studies as necessary for IND filing; TRL5B: Continue establishing correlates of protection, endpoints, and/or surrogate markers for efficacy for use in future GLP studies in animal models. Identify minimally effective dose to facilitate determination of "humanized" dose once clinical data are obtained. Submissions not meeting the TRL 5 maturity requirement will not be reviewed.

In addition, development of mitigators and treatments of other radiological/nuclear incident related medical treatment gaps (e.g., blood products) are also covered under this area of interest.

The current area of interest scope does not currently include the development of field use anti-neutropenics.

Decorporation Agents

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.

4.2 Development of decorporation agents which are either passive (limited generally to the blood pool) or active chelators (preferred; seeks intracellular or distributed depots)

BARDA BAA-16-100-SOL-00001 (CBRN) Page 18 for these isotopes of interest: Co-60, Sr-90, Cs-137, Ir-192, U-235/238, Pu-238/239, and Am-241, other transuranics are of interest but not a priority and are negotiable as secondary efficacy).

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

Thermal Burn MCM

4.3 Development of mitigators or treatments for thermal burn injuries, arising from exposure to the detonation effects of improvised nuclear devices or (INDs) along with ionizing radiation. The technical readiness level for candidates should be at TRL 5 or higher (i.e. completed all activities described for TRL 5); Offerors should have held a pre-IND or pre-IDE or pre-submission meeting with FDA to discuss licensure/clearance/approval as an MCM prior to the submission of a white paper to the BARDA BAA. BARDA may request documentation to support proof of a pre-IND meeting being held and resulting minutes from the agency. Treatments that have efficacy when administered during Definitive Care (as defined above 72 hours post-exposure) are of particular interest.

Thermal burn product categories include Autologous-based, Natural or Manufactured Biologicals, and Ancillary products which enable or enhance the efficacy of treatment.

Ideal products would have market sustainability via clinical indications in conventional care and also address one or more treatment goals in Definitive Care for thermal burns as listed below:

Temporize burn injuries and/or limit burn wound conversion

Aid debridement, excision or visualization of the burn wound depth for quicker and reliable treatment options

Spare autograft; adjunct for autograft to enhance healing, recovery and reduce morbidity

Compatible for use with radiation exposure as demonstrated in a non-clinical model

Technical Point of Contact: Dr. Narayan V. Iyer; narayan.iyer@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 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. dose, schedule, duration, and route of administration)) must be demonstrated. Offerors should have held a pre-IND meeting with the FDA for licensure as an MCM prior to the submission of a white paper to the BARDA BAA. Strong preference will be given to drug candidates that are already approved or are in clinical development for a conventional indication similar to that arising from exposure to a chemical agent. Specific areas of interest within Chemical Threat Medical Countermeasures include:

mailto:mary.homer@hhs.gov mailto:narayan.iyer@hhs.gov

BARDA BAA-16-100-SOL-00001 (CBRN) Page 19

5.1 Pulmonary Agents: Development of MCMs to prevent and treat lung damage (including pulmonary edema and fibrosis) resulting from exposure to agents such as chlorine and phosgene.

5.2 Vesicants: Development of MCMs that limit harmful aspects of exposure to vesicating agents such as sulfur mustard and Lewisite. Needs include MCMs designed to treat lung, skin, and ocular as well as systemic effects.

5.3 Blood/Metabolic Agents: Development of MCMs to treat acute poisoning from agents such as cyanides. Antidotes should be easily administered by first responders in personal protective equipment. Preference is given to those cyanide antidotes that are also effective against smoke inhalation-related exposure.

5.4 Nerve Agents and OP Pesticides: Development of MCMs to treat seizures that are refractory to treatment with benzodiazepines. These drugs, in most cases, will be used after benzodiazepine therapy has failed.

5.5. Novel MCM Delivery Mechanisms: Development of improved methods of administration for new and existing MCMs. The candidates should be amenable to use by emergency medical personnel or first responders dealing with large numbers of exposed individuals in mass casualty situations.

Technical Point of Contact: Dr. Judith Wolfe Laney; judith.laney@hhs.gov

Area of Interest #6: Clinical Diagnostics

Design and production of the system in area of interest #6 must be compliant with U.S.

Quality System Regulation (21 CFR Part 820).

Biodosimetry Diagnostics:

6.1 Development of a dosimetry self-assessment tool in order to determine if an individual has been exposed to ionizing radiation at a dose equal to or greater than 2 Gy.

6.2 Biodosimetry Systems: BARDA is interested in advanced development of a rapid point- of-care diagnostic assay for assessing whether an individual’s absorbed dose of ionizing radiation was above or below 2 Gy, and/or a centralized high-throughput assay system for determining absorbed doses of ionizing radiation in the range of 0.5 Gy to 10 Gy, that have a robust detection signal from 24 hours post-exposure which persists at least one (1) week. The assay system should provide the assessment of the absorbed dose for biodosimetry applications with high sensitivity and specificity. It is preferred for high throughput assays to be developed/optimized for use with existing diagnostic instrument platforms which have a large number of US Clinical lab placements and for point-of-care platforms to be CLIA- waive-able. Minimum technology readiness: TRL-6.

White papers must at a minimum include:

1. Listing of radiation responsive marker(s) and performance data in human and an animal model for each of them.

2. Evidence that a pre-submission meeting has been held with the FDA

3. Instrument and consumable definition and performance data of key components mailto:judith.laney@hhs.gov

BARDA BAA-16-100-SOL-00001 (CBRN) Page 20 or entire system.

4. Listing of all key team members, identifying who will fill each key skill needed to develop, manufacture, and achieve regulatory approval of the product.

5. Functional prototype instrument and consumables in final form.

6.3. Development of an improvement on the current “gold standard” for assessing absorbed doses of ionizing radiation (the dicentric chromosomal assays (DCA)) in terms of ease of use, time for performance, statistical certainty of dose, improved dose range and biomarker lifespan.

Bio-threat Agent Diagnostics:

6.4 Development of an anthrax diagnostic assay system (may be part of a multi-pathogen panel):

6.4.1 Development, clinical evaluation, and/or FDA clearance/approval of rapid, accurate diagnostic systems for determining a Bacillus anthracis infection (anthrax). These systems should be portable and designed for ease-of-use by non-expert personnel at point-of-care (POC) settings. It is preferred that these POC systems be CLIA-waived/waive-able.

6.4.2 Development, clinical evaluation, and/or FDA clearance of centralized, high-throughput diagnostic assay systems for determining a Bacillus anthracis infection (anthrax). It is preferred for high throughput assays to be developed and optimized for use with existing diagnostic instrument platforms that have a large number of US clinical laboratory placements, for use with at least one FDA-cleared “routine health-care” assay.

Notes:

1) For the above, Offerors should provide adequate feasibility data for both the proposed assays and the platform—demonstrating high analytical sensitivity (clinically relevant), specificity, reproducibility, linearity and dynamic range in relevant clinical matrices, such as whole blood. Validated-assay packages will receive higher consideration. (Platform performance data may include testing with surrogate agents, e.g. B. cereus, or relevant “routine health-care” assays).

BARDA is not interested in white papers or proposals that fail to include convincing feasibility data.

2) Submissions made under the above areas of interest 6.4.1 or 6.4.2 should meet TRL 5 or greater (for a detailed list of TRL definitions for diagnostics development see Appendix 1 of this BAA),

6.5 Development, clinical evaluation, and FDA 510(k) clearance of a lateral flow immunoassay device for the detection of Bacillus anthracis Lethal Factor (LF) in whole blood utilizing USG developed antibodies (LF should be detected as both the protein monomer and as part of the anthrax toxin protein complex (LTx)). Device should be CLIA waived or waivable. The Offeror shall improve the sensitivity of the existing

BARDA BAA-16-100-SOL-00001 (CBRN) Page 21 prototype device (currently ~5ng/ml sensitivity for LF) to a >> 2ng/ml sensitivity for LF.

The US Government is able to provide small quantities of purified protein and is able to license the…