BAA-16-100-SOL-00002_FluBAA-Final.pdf

Broad Agency Announcement (BAA) for the Advanced Development of Medical Countermeasures for Pandemic Influenza

BAA-16-100-SOL-00002

Biomedical Advanced Research and Development Authority

(BARDA)

330 Independence Avenue, SW, Room G644

Washington, DC 20201

BARDA Influenza BAA-16-100-SOL-00002 Page 2

Table of Contents

Broad Agency Announcement (BAA) for the Advanced Development of Medical Countermeasures for Pandemic Influenza

INTRODUCTION

OVERVIEW INFORMATION

Agency Name:

Issuing Office:

Development Opportunity Title:

Announcement Type and Date:

Eligible Offerors:

Development 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: Development Areas of Interest Area of Interest #1: Personal Protective Equipment (Mask & Respirators) for Influenza Infection and All-Hazards Area of Interest #2: Full-Featured Continuous Ventilators for Influenza Infection and All-Hazards Area of Interest #3: Influenza and Emerging Infectious Diseases - Test Systems and Diagnostic Tools Area of Interest #4: Influenza Therapeutics Area of Interest #5: Influenza Vaccines

Part II: Development and Technical Objectives Program Management Approach:

Development Approach:

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:

BARDA Influenza BAA-16-100-SOL-00002 Page 3

B. Security Plan:

C. Identification and Disposition of Data:

D. Confidentiality of Information:

E. Publications:

F. Press Releases:

G. Export control notification:

H. Manufacturing Standards:

I. Prohibition on contractor Involvement with Terrorist Activities:

J. Invoices:

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

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

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

Part VIII: Attachments Attachment 1: Technology Readiness Level Criteria Attachment 2: Target Product Profile Template Attachment 3: Regulatory Guidance for Devices Attachment 4: Summary of Related Activities Attachment 5: Quad Chart Format Template Attachment 6: Government Notice for Handling & Submitting Proposals 81

Attachment 7: Breakdown of Proposed Estimated Cost (Plus Fee) and Labor Hours (For Cost Proposal) Attachment 8: Total Life Cycle Costs (TLCC) Definition

BARDA Influenza BAA-16-100-SOL-00002 Page 4

INTRODUCTION

This Broad Agency Announcement (BAA), which sets forth development 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

Development Opportunity Title:

Broad Agency Announcement for the Advanced Development of Medical Countermeasures for Pandemic Influenza

Announcement Type and Date:

Broad Agency Announcement renewal announcement, October 13, 2015 as: BAA-16-

100-SOL-00002

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

Initial Announcement as BARDA-11-100-SOL-00021, issued June 20, 2011 and expired April 10, 2012; and BARDA-12-100-SOL-00018, issued June 8, 2012 and expired June 7, 2013; and BAA-13-100-SOL-00019, issued July 31, 2013 and expired July 30, 2014, BARDA Influenza BAA-16-100-SOL-00002 Page 5 and extended on April 2, 2014 to expire on July 30, 2015, and extended on July 28, 2015 to expire on October 31, 2015.

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 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/

BARDA Influenza BAA-16-100-SOL-00002 Page 6

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 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.

Development Opportunity Description:

The Biomedical Advanced Research and Development Authority solicits the advanced research and development of medical countermeasures to protect the civilian population of the United States against pandemic influenza. BARDA anticipates that research and development activities awarded under this BAA will serve to advance candidate medical countermeasures towards licensure or approval by the Food and Drug Administration

(FDA).

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.

Development Areas of Interest:

1. Personal Protective Equipment (Mask & Respirators) for Influenza Infection and All-Hazards

2. Full-Featured Continuous Ventilators for Influenza Infection and All-Hazards

3. Influenza and Emerging Infectious Diseases - Test Systems and Diagnostic Tools

4. Influenza Therapeutics

5. Influenza Vaccines

Development 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 Development 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

BARDA Influenza BAA-16-100-SOL-00002 Page 7 therapeutics and vaccines (Attachment 1B).

Number of Awards:

Multiple awards of various values are anticipated and are dependent upon the program priorities, proposals’ scientific/technical merits, how well the proposals fit BARDA’s areas of interest, and available 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

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

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

The final White Paper deadline is October 30, 2017.

Receipt confirmation within 1 week.

Decision within 90 calendar days of submission deadline.

Stage 2: Full Proposal As specified in the invitation Letter

Receipt confirmation within 1 week.

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 Flu-BAA@hhs.gov.

Technical questions should be directed to the Technical Point of Contacts (POCs) shown following each development areas of interest. These POC’s are located, in “Part I: Development 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 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 30 October 2017. The submission deadlines are listed above.

mailto:Flu-BAA@hhs.gov

BARDA Influenza BAA-16-100-SOL-00002 Page 9

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 development 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:

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

BARDA Influenza BAA-16-100-SOL-00002 Page 10 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

This Broad Agency Announcement (BAA) sets forth advanced development areas of interest for the Influenza Division of the Office of the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services. 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, 10 U.S.C.§ 2304.

BARDA is the lead Federal agency for the advanced development of medical countermeasures (MCM) to protect the United States against public health emergency threats, including chemical, biological, radiological and nuclear agents, emerging infectious diseases, and pandemic influenza. The Pandemic and All Hazard Preparedness Reauthorization Act directs 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 priorities of the BARDA Influenza Division are closely aligned with the National Strategy for Pandemic Influenza (November 2005), the National Pandemic Influenza Implementation Plan (May 2005), The Public Health Emergency Medical Countermeasures Enterprise Review (August 2010), the President’s Council of Advisors on Science and Technology report on influenza vaccine manufacturing (August 2010), and the BARDA Strategic Plan 2011-2016 (October 2011).

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The 2009 H1N1 influenza pandemic exemplified the unpredictability and rapidity with which a novel influenza strain can impact the world’s population. With a historic effort from both Government and industry partners, vaccines were developed and available to the public six months after the initial outbreak. Despite high infection rates, the 2009 H1N1 virus was only mildly pathogenic, with relatively low rates of accompanying morbidity and mortality in the general population. However, it is possible that future pandemics will feature morbidity and mortality rates comparable with more severe pandemics such as 1918 and 1957. The ever-present and ever-evolving threat of novel influenza subtypes such as H5N1 and H7N9 highlights the need to continue optimizing available medical countermeasures and developing entirely new modalities for prevention and treatment of influenza disease.

Vaccines, therapeutics, diagnostics, ventilators, and respiratory protective devices are essential for protecting all segments of the civilian population from pandemic influenza and other emerging infectious diseases. This BAA will support advanced development activities of medical countermeasures for influenza and other emerging respiratory viruses to be specified by BARDA. BARDA priorities for influenza vaccines are focused on those vaccines that induce long-lasting and broad (heterotypic and/or heterosubtypic) immunity in all populations compared to currently licensed influenza vaccines. In addition, BARDA will prioritize support for vaccines that induce broad immunity so as to prime the population against newly emerging influenza viruses or other respiratory viruses of pandemic potential. 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 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 medical countermeasures and devices suitable for use in at-risk populations such as children, pregnant women, the elderly, and persons with compromised immune systems.

BARDA will endeavor to prioritize projects that provide benefits to all populations while also allowing for focused development projects or studies for at-risk populations where necessary.

BARDA 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:

BARDA Influenza BAA-16-100-SOL-00002 Page 12

The Pandemic and All Hazard Preparedness Act6 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.

113-57, (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 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 committees8 and strategies and reports9 for pandemic influenza.

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

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Part I: Development Areas of Interest

This section presents an overview of the influenza-related 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: Personal Protective Equipment (Mask & Respirators) for Influenza Infection and All-Hazards

Offerors for Area of Interest #1 should describe the maturity level of their proposed technology. The Technology Readiness Level ranking criteria can be found in Attachment 1B of this solicitation. Proposed activities should offer clinical and public health benefits.

1.1 Development and characterization of improved respiratory protective devices (RPD). Support for advanced development of improved RPDs such as masks or respirators to reduce transmission of influenza virus, other infectious agents, and harmful biological hazards. These RPDs should demonstrate improved features over currently available products for functionality, usability, comfort, decontamination and re-use, cost efficiency, manufacturing efficiency, and durability to support a broad population (e.g., pediatric through adult), with a clear path to NIOSH certification and FDA clearance as applicable.

Technical Point of Contact: Rodney Wallace; Rodney.Wallace@hhs.gov

Area of Interest #2: Full-Featured Continuous Ventilators for Influenza Infection and All-Hazards

Offerors for Area of Interest #2 should propose activities for products which can currently be described as having a maturity level equal to or greater than Technology Readiness Level (TRL) 6. A product can be described as achieving a TRL if it has completed all activities identified in that TRL. The Technology Readiness Level ranking criteria can be found in Attachment 13B of this solicitation. Proposed activities should offer beneficial clinical and public health impact.

2.1 Development of improved full-featured continuous ventilators. Advanced development of new or improved ventilators to provide respiratory support in clinical care, transport, and emergency use settings for severe respiratory conditions resulting from influenza infections or all-hazards incidents. Ideal ventilators should be portable, support neonate (≥ 2.5kg) to adult populations, be capable of operation by unskilled or minimally trained care providers, use universal components, include considerations for ease of stockpiling/maintenance, accommodate/provide accessories typically used in ventilator standard of care, have a low cost per unit (<$4,000 per fully kitted unit), and accommodate domestic surge production capacity.

mailto:Rodney.Wallace@hhs.gov

BARDA Influenza BAA-16-100-SOL-00002 Page 14

Technical Point of Contact: Rodney Wallace; Rodney.Wallace@hhs.gov

Area of Interest #3: Influenza and Emerging Infectious Diseases - Test Systems and Diagnostic Tools

Offerors for Area of Interest #3 should propose activities for products which can currently be described as having a maturity level equal to or greater than the Technology Readiness Level (TRL) 6 unless otherwise indicated. A product can be described as achieving a TRL if it has completed all activities identified in that TRL. For diagnostics, two TRL criteria are provided in Attachments 1A and 1B of this solicitation; Offerors may use either one to rate the maturity of their technology. Design, manufacturing, and assembly of reagents and system components proposed must be consistent with U.S.

Quality Systems Regulations (21 CFR Part 820) and use in CLIA-regulated laboratories.

Proposed activities should offer beneficial clinical and public health impact.

3.1 Development of improved specimen collection materials and methods which enable reliable and consistent self-collection, or collection by non-expert personnel for testing on-site, or for drop-off transfer. Approaches should enable direct testing (e.g., detecting viral antigen and nucleic acids) and testing on-site with rapid turn-around time of results to guide clinical decisions and follow-up.

3.2 Development of advanced sequencing methods:

3.2.1 Development of methods for identifying novel influenza viruses and other emerging respiratory viruses. Advanced development and implementation of methods applying targeted or whole genome nucleotide sequencing for characteristic influenza gene segments to enable more rapid identification of human-animal reassortant influenza viruses, with the goal to diagnose and recognize both seasonal and novel influenza infections.

3.2.2 Simplification of Next Generation Nucleotide Sequencing Platforms and Analysis Tools. Advanced development and implementation of prototypes to next generation sequencing platforms and analysis tools, making them appropriate for use in CLIA regulated laboratories. Proposals should include advanced development and implementation of a diagnostic for Influenza, including pandemic and seasonal strain identification using these prototyped tools.

3.3 Rapid identification of antiviral drug resistant influenza viruses. Advanced development of diagnostic tests and methods to rapidly identify reduced antiviral drug susceptibility by direct specimen testing and standardize functional drug resistance testing with interpretive criteria that can be correlated to clinical outcomes in patients with influenza infections.

3.4 Identification of prognostic marker(s) of influenza infection, both symptomatic and pre-symptomatic, and development of rapid diagnostic tests that can guide earlier interventions for at-risk individuals. Mature technologies with a track record of successful biomarker identification will be given priority over less mature technologies.

3.5 Development of home use or point of care Influenza diagnostics tests, to be used as part of an integrated clinical assessment strategy. For use in home, pharmacy, outpatient practice, and/or community settings to prompt earlier consideration for antiviral drug use and precautions particularly for at-risk individuals to improve clinical mailto:Rodney.Wallace@hhs.gov

BARDA Influenza BAA-16-100-SOL-00002 Page 15 outcomes and maximize pandemic and seasonal control. Critical technology component should be at a maturity level equal to or greater than TRL 4.

3.6 Studies to demonstrate the value of using Influenza diagnostics in clinical practice, emergency room operations, or community settings to improve reliability and timeliness of diagnosis and effective use of therapeutics. Studies of interest would demonstrate the improvement in quality or cost effectiveness of care due to inclusion of diagnostics in the treatment algorithm for influenza patients or studies that demonstrate the value of antiviral resistance testing in ensuring appropriate use of antivirals.

Technical Point of Contact: Rodney Wallace; Rodney.Wallace@hhs.gov

NOTE: Development programs at lower maturity levels should consider funding opportunities offered by The National Institute of Allergy and Infectious Diseases (NIAID) or other Federal agencies that fund earlier stage research and development projects.

Learn more about NIAID diagnostics resources10.

Technical inquiries about funding through NIAID programs can be directed to:

DMIDResources@niaid.nih.gov

Area of Interest #4: Influenza Therapeutics

Offerors for Area of Interest #4 should propose activities for products having a maturity level equal to or greater than Technology Readiness Level (TRL) 6 (as evidenced by release of a finalized report for a Phase 1 clinical study), unless otherwise indicated. A product can be described as achieving a TRL if it has completed all activities identified in that TRL. The Technology Readiness Level ranking criteria can be found in Attachment 1C of this BAA.

BARDA seeks to develop novel antiviral therapeutics for the treatment of influenza A and B infections, as well as for the treatment of disease caused by emerging respiratory viruses of pandemic potential to be determined by BARDA. Specifically for influenza therapeutics, BARDA prefers a novel mechanism of action that precludes the rapid emergence of drug resistance and with proven broad influenza strain activity (minimum for influenza A: H1N1, H2N2, H3N2, H5N1, and H7N9). Combination therapeutics that include novel investigational compounds and licensed therapeutics would also be applicable. Please address the Combination Rule if a combination therapy is proposed.

Demonstration of efficacy as measured by a significant reduction in morbidity, mortality, or viral titers (for example) in relevant influenza infection animal models is required.

Because there are no treatments approved for severely ill, hospitalized influenza patients, the strongest proposals will include a clinical development plan that addresses treatment of this population. The strongest proposals will also have data that demonstrates significant antiviral activity when given later in the course of disease (48- 96 hours after symptom onset) or that demonstrates improved efficacy when compared to neuraminidase inhibitors and in viruses resistant to current therapies. Therapeutics that offer benefit to special populations, such as pediatrics and the elderly will be viewed more favorably. Therapeutics must have an active Investigational New Drug application filed with the FDA and have demonstrated safety in a Phase 1 study as evidenced by a final clinical study report.

http://www.niaid.nih.gov/topics/diagnostics/Pages/Default.aspx mailto:Rodney.Wallace@hhs.gov http://www.niaid.nih.gov/topics/diagnostics/Pages/Default.aspx mailto:DMIDResources@niaid.nih.gov

BARDA Influenza BAA-16-100-SOL-00002 Page 16

4.1 Small molecule antivirals. For influenza indication, small molecule antivirals must have a novel mechanism of action and demonstrate advantages when compared to FDA approved antivirals against influenza. Demonstration of efficacy 48-96 hours after appropriate viral challenge in animal models is required. Therapeutics with antiviral activity at later time points will be viewed more favorably. The strongest proposals will have data demonstrating activity against strains from both influenza A and B viruses.

BARDA may request responses to this BAA for small molecule antiviral drugs against specific emerging respiratory viruses of pandemic potential. BARDA will prioritize small molecule antiviral candidates against specified emerging infectious diseases that have reached the TRL6 level, however, earlier stage candidates may be considered.

4.2 Immunotherapeutics. Monoclonal antibody therapeutics developed for the treatment of influenza or other respiratory viruses of pandemic potential to be determined by BARDA should have virus neutralizing activity. For example, for influenza A, monoclonal antibodies that are broadly neutralizing across Group 1 and Group 2 influenza A strains are most desirable, followed by antibodies that neutralize Group 1 or Group 2 influenza A strains individually. For influenza B, monoclonal antibodies that are broadly neutralizing across both influenza B lineages is desired. Demonstration of efficacy 48-96 hours after appropriate viral challenge in animal models is required.

Therapeutics with antiviral activity at later time points will be viewed more favorably.

Advanced development of platform technologies capable of rapidly screening and optimizing monoclonal antibodies against influenza are also desirable. BARDA may specify responses to this BAA for immunotherapeutics against specific emerging respiratory viruses of pandemic potential. BARDA will prioritize immunotherapeutics candidates against specified emerging infectious diseases that have reached the TRL6 level, however, earlier stage candidates may be considered.

4.3 Immunomodulators. Immunomodulators that improve the clinical response to and/or resolution of symptoms associated with influenza or emerging viral infection will be considered. Product candidates must show demonstration of efficacy as measured by a significant reduction in morbidity, mortality, viral titers, or a significant change in immunological markers (for example) in relevant influenza infection animal models.

Proposed candidates must have an active Investigational New Drug application filed with the FDA and have demonstrated safety in a Phase 1 study as evidenced by a final clinical study report.

Technical Point of Contact: Melissa Willis; Melissa.Willis@hhs.gov

NOTE: Development programs at a maturity level less than TRL6 should consider funding opportunities offered by The National Institute of Allergy and Infectious Diseases (NIAID) or other Federal agencies that fund earlier stage research and development projects.

Learn more about NIAID therapeutics resources11.

Technical inquiries about funding through NIAID programs can be directed to:

DMIDResources@niaid.nih.gov http://www.niaid.nih.gov/LabsAndResources/resources/dmid/Pages/therapeutics.aspx mailto:Melissa.Willis@hhs.gov http://www.niaid.nih.gov/LabsAndResources/resources/dmid/Pages/therapeutics.aspx

BARDA Influenza BAA-16-100-SOL-00002 Page 17

Area of Interest #5: Influenza Vaccines

Offerors for Area of Interest #5 should propose activities for products that can currently be described as having a maturity level equal to or greater than Technology Readiness Level (TRL) 6 (e.g. as evidenced by release of a finalized report for a Phase 1 clinical study for the same indication as proposed activities), unless otherwise specified. A product can be described as achieving a TRL if it has completed all activities identified in that TRL. The Technology Readiness Level ranking criteria can be found in Attachment 1C of this BAA.

Under this Area of Interest, BARDA is seeking technologies that will improve preparedness against influenza and emerging infectious diseases with pandemic potential. Successful offerors will provide evidence of vaccine approaches that show improvement in key vaccine attributes as compared to currently available products.

5.1 Advanced development of more effective influenza vaccine candidates which have achieved TRL 6 or greater. Specifically for influenza, support for advanced development of new influenza vaccine candidates with the potential to stimulate broader (across influenza subtypes and/or within influenza subtypes), durable and more effective immunity than currently licensed products. The offeror should provide data or a plan for validation of novel vaccine potency and release assays that are specific for the new influenza vaccine candidate. The offeror should provide a regulatory strategy for FDA approval of the candidate and data demonstrating statistically-relevant improvements in immunogenicity/efficacy as compared to existing FDA licensed vaccines. Proposed clinical activities (Phase 1b/Phase 2 studies) should support development toward FDA licensure and evaluate key vaccine attributes, such as dose schedule, mechanism of action, time to onset of protection, induction of improved immunogenicity, broader cross-protection across influenza A virus subtypes, induction of priming immunity against viruses of pandemic potential and duration of protection. Efforts might include qualification and validation of clinical sample assays for novel correlates of protection used to evaluate the immune response to the new influenza vaccine candidate. BARDA may request responses to this BAA for vaccine against specific emerging respiratory viruses of pandemic potential. BARDA will prioritize vaccine candidates against specified emerging infectious diseases that have reached the TRL6 level, however, earlier stage candidates may be considered.

5.2 Vaccine production enhancements. Support for improvements in vaccine production methods that accelerate the availability of vaccines against viruses with pandemic potential. Enhancements include but are not restricted to, development or implementation of new candidate vaccine and seed viruses that promote high-yield or improved cross-reactivity, rapid production of assay reference materials or reagents or methods to decrease the time required to produce such materials, development or implementation of new potency determination methods that relieve reagent production time dependencies and methods to improve manufacturing yields.

Technical Point of Contact: Armen Donabedian; Armen.Donabedian@hhs.gov

Development programs at a maturity level less than TRL 6 should consider funding opportunities offered by The National Institute of Allergy and Infectious Diseases (NIAID) or other Federal agencies that fund earlier stage research and development projects.

mailto:Armen.Donabedian@hhs.gov

BARDA Influenza BAA-16-100-SOL-00002 Page 18

Learn more about NIAID vaccine resources12.

Technical inquiries about funding through NIAID programs can be directed to:

DMIDResources@niaid.nih.gov http://www.niaid.nih.gov/LabsAndResources/resources/dmid/vaccine/Pages/default.aspx http://www.niaid.nih.gov/LabsAndResources/resources/dmid/vaccine/Pages/default.aspx

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Part II: Development and Technical Objectives

The topics listed below exemplify some of the typical activities undertaken during a drug, biologic or device development effort in the areas of non-clinical studies, manufacturing, clinical evaluation, project management, and regulatory strategy. This information is provided to assist and guide Offerors in preparing their White Papers and Full Proposal Statements of Work (SOW).

Offerors should submit information in their White Paper and Full Proposal that addresses these topics as appropriate, and should provide as much detail as may be necessary to fully explain and justify the proposed technical approach or method. Offerors should propose a SOW consistent with activities for the Technology Readiness Level indicated for each Development Area of Interest in Part I. The SOW must be presented in discrete segments that are non-severable in their activity.

Proposal preparation and submission instructions are contained in Part V, VI, and VII.

Program Management Approach:

Program Management Representative Activities may also include but are not limited to:

a. Identification of and management to, distinct stages of the product development pathway that are gates for Go/No Go decisions for advancing to the next stage of the Integrated Product Development Plan.

b. Establishment of and tracking of milestones and timelines for the initiation conduct, and completion of product development activities for each stage with a budget (in direct costs) linked to each stage.

c. Ongoing evaluation of qualitative and quantitative criteria and accompanying data used to assess the scientific merit and technical feasibility of proceeding to the next stage of product development.

d. Maintaining and managing staff (in-house and contracted) to assure the necessary expertise and dedicated effort to perform the work.

e. Directing and overseeing subcontractors and consultants to assure successful performance of planned activities within the cost and schedule constraints of the contract.

f. Conducting performance measurement that shall include establishing an initial plan; defining measurable parameters; defining how these parameters relate to cost and schedule impacts; their approach in providing a detailed schedule that generates a critical path for the project; and a description of the cost- accounting system used or intended to be used based on budget estimates to monitor all costs related to the contract award for both prime-and sub- contractors on a real time bases.

g. Perform assessments of technical approaches to reduce the Total Life Cycle Cost (TLCC) for the proposed countermeasure throughout the products life cycle and identify strategic approaches to ensure the product has a sustainable commercial value to ensure long term access to the medical countermeasure.

Development Approach:

Personal Protective Equipment (Masks & Respirators) and Full-Featured

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Continuous Ventilator for Influenza Infection and All-Hazards Activities may also include but are not limited to:

a. Integration and Verification:

Establish technical specifications based on design controls.

Establish qualification of components and accessories.

Produce pre-production (beta) prototype.

b. Internal and External Validation Studies:

Design and validate performance test protocols and acceptance criteria (e.g., bench, animal and/or clinical studies) to enable standardized safety and effectiveness measures.

Conduct field evaluations of PPEs to filter influenza viruses and other respiratory hazards.

Conduct field evaluations of ventilators to provide respiratory support in comparison to predicate devices on the market.

c. Manufacturing:

Produce pilot or finished lots of test units in sufficient quantities for clinical and non-clinical evaluations.

Maintain appropriate quality assurance with processes, procedures, and documentation consistent with design controls (as applicable), Quality Systems, and relevant standards (e.g., deviation and risk management strategies).

Identify critical manufacturing process parameters for domestic scale-up production.

d. Other Product Development Activities:

Collaborate with relevant technical guidance and standards organizations to develop consensus test methods and parameters.

Provide equipments and/or necessary materials along with technical support to programs evaluating the safety and effectiveness of these devices in relevant environments.

Evaluate therapeutic value of ventilator features for assisting clinical decisions.

Design and coordinate conduct of clinical evaluations including device performance and usability by non-skilled or minimally trained care providers in collaboration with institutional or public health programs.

Incorporate universal breathing circuits and interoperable ventilator accessories for increased compatibility with broad range of accessory components.

Influenza Test Systems and Diagnostic Tool Activities may also include but are not limited to:

a. Integration and Verification:

Establish QA criteria based on implemented design controls.

Produce pre-production (beta) instrument platform

Initiate accelerated and real-time stability studies

Establish technology transfer agreements and implement qualification of sourced…