Flu BAA FINAL 2012.docx

BARDA INFLUENZA BAA-12-100-SOL-00018

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 G640, 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, 330 Independence Avenue SW, Rm G640, Washington, DC, 20201

Research Opportunity Title: BARDA Broad Agency Announcement for the Advanced Development of Medical Countermeasures for Pandemic Influenza

Announcement Type and Date:

Broad Agency Announcement renewal, June 8, 2012, BARDA INFLUENZA BAA-12-100-SOL-00018.

Initial Announcement as BARDA BAA-11-100-SOL-00021, issued June 20, 2011 – expired April10, 2012.

Eligible Applicants: This BAA is open to ALL responsible sources. Offerors may include private sector organizations, Federal, State or Local Government laboratories, Federally Funded Research and Development Centers (FFRDCs), academic institutions, and other non-for-profit organizations. Offerors have the option of creating teams with other organizations.

Federally Funded Research and Development Centers (FFRDCs) are eligible to respond to this BAA, individually or as a team member of an eligible principal Offeror, so long as they are permitted to do so under the sponsoring agreement between the Government and the specific FFRDC.

To be eligible for award, a prospective recipient must meet certain minimum standards pertaining to financial resources, as well as a demonstrated ability to accomplish the proposed performance schedule. The Offeror must also demonstrate the following capabilities: a prior record of performance, integrity, organization, experience, operational controls, technical controls, technical skills, facilities, and equipment.

Historically Black Colleges and Universities (HBCU), Minority Institutions (MI), Small Business concerns, Small Disadvantaged Business concerns, Women-Owned Small Business concerns, Veteran-Owned Small Business concerns, Service-Disabled Veteran-Owned Small Business concerns, and HUB Zone Small Business concerns are encouraged to submit proposals and to join other entities as team members in submitting proposals.

Research 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).

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

BARDA INFLUENZA BAA-12-100-SOL-00018

Table of Contents

Attachment 1: Overview Information

Attachment 2: Development Areas of Interest

Attachment 3: Technical Objectives

Attachment 4: Reporting Requirements and Deliverables

Attachment 5: Proposal Preparation and Submission

Attachment 6: Quad Chart, White Paper, and Full Proposal Evaluation

Attachment 7: Reserved

Attachment 8: Reserved

Attachment 9: Reserved

Attachment 10: Reserved

Attachment 11: Reserved

Attachment 12: Pre-Proposal Conference Notice

Attachment 14: Breakdown of Proposed Estimated Costs (Plus Fees) and Labor Hours

Attachment 15: Security Template

Attachment 16: Summary of Related Activities

Attachment 17: Government Notice for Handling Proposals

Attachment 18: Quad Chart Template

Attachment 19: Target Product Profile Template

Attachment 20: Regulatory Guidance for Devices

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

Attachment 1: Overview Information

INTRODUCTION

This Broad Agency Announcement (BAA) sets forth advanced development areas of interest for the Office of the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS). This BAA is issued under paragraph 6.102(d)(2) of the Federal Acquisition Regulation (FAR), and proposals selected for award are considered to be the result of full and open competition and in full compliance with the provision of Public Law 98-369, "The Competition in Contracting Act of 1984" and subsequent amendments.

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 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).

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 pandemic influenza presents a compelling need to optimize available medical countermeasures and develop entirely new modalities for prevention and treatment of influenza disease.

Vaccines, therapeutics, diagnostics and devices are essential for protecting all segments of the civilian population. This BAA will support advanced development activities to mature candidate products and to better address considerations of the challenging lifecycle requirements of these products before and during a pandemic (e.g. shelf life, storage, distribution, and dispensing). Additional focus will be placed on supporting the development of 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.

GUIDANCE FOR POTENTIAL OFFERORS

Areas of Interest This BAA solicits proposals that focus on one or more of the following areas of interest as listed here and further described in Attachment 2 of this announcement.

Development Areas of Interest:

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

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

3. Clinical Influenza Test Systems and Diagnostic Tools

4. Influenza Therapeutics

5. Influenza Vaccines

Technical objectives are described in Attachment 3, and Offerors may propose activities in one or more areas (e.g., Non-Clinical Product Development, Manufacturing Process Development, Formulation, 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 be consistent with the requirements of the given Development Area of Interest. In addition, each White Paper should contain sufficient supporting information to justify the TRL rating. Criteria for determining the appropriate TRL level for a product can be found in Attachment 13. Please 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 vaccines and therapeutics, one with devices, and two TRL documents are provided to evaluate diagnostics products and to provide Offerors greater insight into the complexities of the diagnostics development process. Either diagnostics TRL criteria document may be used to assess the maturity of a diagnostics product.

Application Process The BAA will be conducted in two stages:

In Stage 1, Offerors shall submit a Quad Chart and White Paper summarizing the proposed project. All Quad Charts and White Papers must be prepared in accordance with the instructions contained in Attachment 5. Brochures or other descriptions of general organizational or individual capabilities will not be accepted. Electronic acknowledgement of receipt of White Papers will be made within one week.

For Stage 1, there are four quarterly deadlines: September 1, 2012; December 1, 2012; March 1, 2013 and June 7, 2013 at 3 PM EST on each date. Offerors who submit White Papers after a given deadline may not have their materials reviewed until after the next deadline. Quad Charts and White Papers will not be accepted after 3:00 PM Eastern Standard Time on June 7, 2013.

Following BARDA review, decision letters will be sent to Offerors within 90 calendar days after the deadline with a decision to invite or not invite for a Stage 2 Full Proposal.

In Stage 2, Offerors receiving a favorable Stage 1 evaluation will be invited to submit a Full Proposal to BARDA by a date specified by the Contracting Officer in the proposal invitation letter. Instructions for completing the Full Proposal are found in Attachment 5 of this announcement. A request to submit a Full Proposal is not a guarantee of an award. Reimbursement of Full Proposal preparation costs will not be approved.

The success of a product development program requires a relentless focus on the desired characteristics of the resulting medical countermeasure product or device. As a component of a Full Proposal submission, Offerors are requested to provide a Target Product Profile if applicable. A template for a Drug Target Product Profile is included in Attachment 19 as a tool for Offerors to describe the objectives of their advanced research and development activities, and to update dynamically as supporting data about their product or project is obtained. All Offerors are encouraged to submit a Target Product Profile for the proposed medical countermeasure or device, with a particular focus on elements 1-4. For those products for which the Target Product Profile format is not applicable, appropriate equivalent information regarding the desired outcome of the proposed development activities should be provided.

There are no specified funding limitations identified for individual proposals submitted under this BAA. The budget shall be commensurate with the nature and complexity of the proposed activities; however, contract awards and level of funding may be impacted by the availability of Congressional annual and/or supplemental appropriations. The costs of preparing responses to this BAA are not considered an allowable direct charge on any resultant award.

Communicating with BARDA In an effort to more effectively meet its mission, BARDA has developed a Technology Watch seminar series where product developers can meet with US Government staff and present their candidate technologies. During these talks, Government officials can provide informal feedback on product development activities. Before applying for this solicitation, product developers are highly encouraged to provide a Technology Watch seminar at BARDA. Product developers can request to schedule a seminar at:

https://www.medicalcountermeasures.gov/Request-Meeting.aspx

BARDA realizes that the preparation of a research 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 to make preliminary inquiries as to the appropriateness of their technology to this solicitation before preparing a Quad Chart and White Paper. Offerors contemplating submitting Quad Charts and White Papers are strongly encouraged to contact BARDA technical staff at FLU-BAA@HHS.GOV. In order to ensure a timely response, the subject line of each e-mail must include either the Development Area of Interest in question, or “ADMIN” to indicate administrative and process questions. Please include all necessary contact information with any inquiry.

Once a White Paper or Full Proposal has been submitted, all communications should be conducted with the Contracting Officer in the BARDA Contracting Office (The Office of Acquisition Management, Contracts & Grants). Offerors are advised that only a Contracting Officer may obligate the Government to any agreement involving expenditure of Government funds.

Contractual Guidance In accordance with Federal statutes, regulations, and HHS policies, no person on grounds of race, national origin, color, religion, sexual orientation, gender identity, disability (physical or mental), age, status as a parent, or genetic information 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 HHS.

ASPR reserves the right to fund all, some, or none of the proposals submitted. While awards are anticipated to occur according to the stated schedule, Offerors that are not responsive to BARDA requests for information in a timely manner, or fail to meet Government deadlines established and communicated with each request, may be removed from award consideration.

ASPR 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.

Offerors should follow the instructions provided in Attachment 5 of this BAA, along with any additional instructions provided by the Contracting Officer.

Anticipated funding for this solicitation (not per contract or per award) may range from $2M to $300M subject to Congressional appropriations. This funding amount does not reflect potential funding amounts for single contract awards. This funding profile is an estimate only and does not represent a contractual obligation for funding. All funding is subject to change due to Government discretion and availability. Multiple awards of various values are anticipated and are dependent upon the proposals’ scientific and technical merits applicability to BARDA’s areas of interest and prioritized program objectives, and available funding.

The purpose of this BAA is to support advanced development of medical countermeasures for pandemic influenza. This solicitation does not include any provisions for acquisition of products. Support for advanced development of any particular product through this solicitation should not be viewed as a precursor to a future acquisition. Offerors should therefore assume the responsibility for developing a commercial market for any product developed using BARDA funding.

All administrative and technical inquires regarding this BAA shall be addressed to FLU-BAA@hhs.gov. In order to ensure a timely response, the subject line of each e-mail must include either the Development Area of Interest in question, or “ADMIN” to indicate administrative and process questions. Please include all necessary contact information with any inquiry.

This BAA is available on the following websites:

https://www.fbo.gov https://www.medicalcountermeasures.gov/ http://www.phe.gov/

This BAA is a continuously open announcement valid throughout the period from the date of issuance through June 7, 2013, unless announced otherwise. Amendments to this BAA will be posted to the websites listed above when they occur. Interested parties are encouraged to check these websites regularly for updates and amendments.

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

BARDA INFLUENZA BAA-12-100-SOL-00018

Attachment 2: 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 Attachment 3: Technical Objectives.

Offerors contemplating submitting quad charts and white papers are strongly encouraged to contact BARDA technical staff at FLU-BAA@HHS.GOV. In order to ensure a timely response, the subject line of each e-mail must include either the Development Area of Interest in question, or “ADMIN” to indicate administrative and process questions.

Area of Interest #1: Personal Protective Equipment (Mask & Respirators) for Influenza Infection and All-Hazards Offerors for Area of Interest #1 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.

1.1 Development and characterization of improved personal protective equipment such as masks or N95 respirators to prevent influenza infections or harmful effects of all-hazards events.

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 life support in clinical and non-clinical environments for severe respiratory conditions resulting from influenza infections or all-hazards events. Ideal ventilators should support neonate to adult populations, be capable of operation by unskilled or minimally trained care providers, include considerations for ease of stockpiling/maintenance, accommodate/provide accessories typically used in ventilatory standard of care, have a low cost per unit (<$3,000 per fully-kitted unit), and accommodate domestic surge production capacity.

Area of Interest #3: Clinical Influenza 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) indicated below. 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 13A and 13B 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 better rapid influenza diagnostic tests. To include: Advanced development of new or improved rapid tests, including point of care (POC) type tests that facilitate more timely diagnosis of influenza infections in outpatient/ambulatory healthcare practices. Ideal tests would have a simplicity level that could enable home use, or use in minimally resourced settings. Critical technology component should be at a maturity level equal to or greater than TRL 6.

3.2 Development of improved respiratory specimen collection materials and methods. Approaches should enable direct testing (using viral antigen or nucleic acids) and evaluation in on-site laboratories, with available transport systems to maintain viability and nucleic acid integrity for reference and confirmatory testing. Materials and methods can enable reliable and consistent self-collection or collection by non-expert personnel.

3.3 Development of expanded respiratory pathogen tests on existing test platforms. Transfer and validation to existing platforms of established molecular or other target signatures for influenza and other respiratory pathogens. Critical technology component should be at a maturity level equal to or greater than TRL 8.

3.4 Development of advanced sequence detection methods for identifying novel influenza strains. Advanced development and implementation of methods applying targeted or whole genome sequencing for known influenza reassortant genes to enable more rapid identification of human-animal reassortant influenza viruses, with the goal of diagnosis of unusual influenza infections. Critical technology component should be at a maturity level equal to or greater than TRL 6.

3.5 Rapid identification of antiviral resistant influenza strains. Advanced development of reagents for reference methods to identify antiviral resistance and standardize functional resistance testing; adaptation of these methods for use in clinical hospital laboratories, with interpretive criteria correlating to clinical outcomes in patients with antiviral resistant infections.

3.6 Rapid identification of influenza immunological response. Advanced development and evaluation of methods to rapidly determine presence/absence of significant circulating antibodies specific for influenza viruses; or adaptation of such methods, procedures, standards and controls to an OTS platform for use in clinical and research laboratory settings. Critical technology component should be at a maturity level equal to or greater than TRL 6.

3.7 Development and characterization of stable diagnostic reagents or reference material and controls, for application with existing diagnostic test systems on established platforms. Capability should be available for maintaining inventories and assuring stability sufficient to enable rapid distribution on-demand (including to remote locations), and capability for rapid surge production and modified reagents for additional targets. Critical technology component should be at a maturity level equal to or greater than TRL 8.

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.

Information about NIAID resources can be found at:

http://www.niaid.nih.gov/topics/diagnostics/Pages/funding.aspx

Area of Interest #4: Influenza Therapeutics Offerors for Area of Interest #4 should propose activities for products which alone or in combination 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 13C of this BAA.

4.1.2 Development of combination therapeutic approaches using influenza antivirals which individually have achieved TRL 6 or greater. Combination therapies should utilize drugs with different mechanisms of action to reduce the risk of resistance development and to increase the potential for synergistic treatment effects. The contribution of each component is relevant and the combination of drugs should be superior to individual components when administered as a single drug.

4.1.4 Activities to support identification and validation of surrogate endpoints to predict clinical benefits in patients treated with influenza antiviral therapeutics. Virology and non-virology parameters that reliably predict clinical outcomes in influenza trials that are being conducted to evaluate influenza antivirals at TRL 6 or greater are of high interest. Surrogate endpoints should facilitate accelerated approval of novel anti-influenza treatments, emergency use authorization mechanisms and risk-benefit evaluation.

4.2.2 Therapeutics at TRL6 or greater targeting host factors that result in reduced influenza virus replication and amelioration of symptoms. Immunomodulatory therapeutics and host factors critical for viral replication are examples of targets that could lead to broad-spectrum antiviral activity against influenza and other relevant human viral diseases. The available data package must support a TRL 6 or greater designation for treatment of influenza. Advanced development activities should focus on treatment of influenza with strategies to expand into multi-purpose, broad- spectrum antiviral indications.

4.2.3 Development of combination therapeutic approaches using an influenza antiviral and a host modulating therapeutic for control of severe influenza disease. The contribution of each component is relevant and the combination of drugs should be superior in amelioration of symptoms to the individual. The individual therapeutics being used should be supported by sufficient data to initiate advanced development for an influenza indication at TRL6 or greater.

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.

Information about NIAID resources can be found at:

http://www.niaid.nih.gov/LabsAndResources/resources/dmid/Pages/therapeutics.aspx Technical inquiries about funding through NIAID programs can be directed to: DMIDResources@niaid.nih.gov

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). 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 13C of this BAA.

5.1 Advanced development of novel recombinant influenza vaccine candidates which have achieved TRL 6 or greater.

5.1.1 Support for advanced development of novel hemagglutinin-based molecular and recombinant influenza vaccine candidates for influenza A virus subtypes with pandemic potential (i.e., animal and/or human influenza A viruses that are circulating in wild birds and/or domestic animals that cause, or have significant potential to cause, sporadic or ongoing human infections, or that have historically caused pandemics in humans, or have mutated to cause pandemics in humans, and for which the majority of the population is immunologically naïve). Proposed activities should enable improvements to key vaccine attributes, including formulation and delivery methods, dose schedule, time to onset of protection, induction of improved immunogenicity, broader cross-protection across influenza A virus subtypes, duration of protection, storage conditions, shelf-life, and safety and immunogenicity in at-risk populations (pediatric, elderly, and/or immunocompromised persons).

5.1.2 Support for advanced development of hemagglutinin-based influenza vaccine candidates that elicit immunogenicity and efficacy in humans against a range of antigenically-divergent influenza A virus subtypes and/or immunogenicity and efficacy in humans against multiple influenza subtypes. Proposed activities should include the demonstration of significant immune responses in humans against different influenza subtypes as ascertained from hemagglutination inhibition and microneutralization assays.

5.2 Advanced development of adjuvanted influenza vaccine candidates which have achieved TRL 6 or greater. Support for advanced development of improved adjuvants used in combination with influenza vaccines against pandemic viruses or viruses with pandemic potential as described above. Use of approved or novel adjuvants in conjunction with a specific influenza vaccine to achieve enhanced or broadened immunogenicity and efficacy against multiple influenza subtypes, dose reduction, enhanced humoral and/or cellular immunity, improved safety and tolerability profiles, and/or improved performance in at-risk populations, such as pediatric, elderly or immunocompromised individuals. Product candidates under development must have achieved a maturity of TRL 6 or greater in combination as indicated for influenza.

5.3 Enhancements to vaccine production capabilities. Support for improvements in vaccine and reagent production methods, including seed virus production, rapid production of reference materials or reagents or methods to decrease the time required to produce such materials, yield improvements, purification methods, potency determination, and sterility testing.

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.

Information about NIAID resources can be found at:

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

Technical inquiries about funding through NIAID programs can be directed to: DMIDResources@niaid.nih.gov

Offerors contemplating submitting quad charts and white papers are strongly encouraged to contact BARDA technical staff at FLU-BAA@HHS.GOV. In order to ensure a timely response, the subject line of each email must include either the Development Area of Interest in question, or “ADMIN” to indicate administrative and process questions.

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

Attachment 3: 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 Attachment 2. The SOW must be presented in discrete segments that are non-severable in their activity.

Proposal preparation and submission instructions are contained in Attachment 5.

A. Development Approach:

Personal Protective Equipment (PPE) and Full-Featured Continuous Ventilator Activities may also include but are not limited to:

a. Integration and Verification:

0. Establish technical specifications based on design controls.

0. Establish qualification of components and accessories.

0. Produce pre-production (beta) prototype.

b. Internal and External Validation Studies:

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

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

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

c. Manufacturing:

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

0. 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).

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

d. Other Product Development Activities:

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

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

0. Evaluate therapeutic value of ventilator features for assisting clinical decisions.

6. 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.

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

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

a. Integration and Verification:

0. Establish QA criteria based on implemented design controls.

7. Produce pre-production (beta) instrument platform

7. Initiate accelerated and real-time stability studies

7. Establish technology transfer agreements and implement qualification of sourced reagents, components, and materials.

b. Internal and External Validation Studies:

0. Develop assessments of specimen processing methods and specimen target stability using modified or new collection and transport materials.

8. Collaborate with clinical entities to assess feasibility for use of specific specimen collection methods.

0. Optimize new or modified assays on existing platforms.

0. Design and validate protocols for analytical and clinical studies to enable standardized performance measures.

0. Perform field evaluations with rapid in vitro diagnostic test systems to detect and identify influenza viruses and optionally distinguish other respiratory pathogens.

c. Manufacturing:

0. Produce pilot or finished lots of test units (e.g., cartridges, assay plates) in sufficient amounts for clinical and non-clinical evaluations

0. 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).

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

d. Other Product Development Activities:

0. Use publicly available gene sequences in collaboration with CDC, NIH and others with advanced influenza genetic informatics expertise to characterize influenza viruses for device, assay, or test design.

0. Collaborate with guidance and standards organizations to develop laboratory and practice guidance or standards for specific methods.

0. Evaluate specimen types, test methods, and testing algorithms for assessing positive and negative likelihood ratios of influenza infections in specific clinical settings.

0. Evaluate diagnostic value of respiratory disease test methods for informing clinical management decisions.

0. Provide equipment, reagents and necessary materials along with technical support, as requested, to programs monitoring influenza prevalence and characterizing circulating virus types, subtypes, and resistance.

16. Design and coordinate clinical evaluations in collaboration with institutional or public health programs to monitor influenza virus and other respiratory pathogens causing community respiratory disease outbreaks.

16. Validate clinical assessment strategies for guiding influenza testing decisions in outpatient practice, to include at-risk groups (e.g., pediatrics and obstetrics).

Antiviral Advanced Research and Development Representative Activities may include but are not limited to:

Antiviral Process Development, Formulation, and Manufacturing Development Representative Activities may include but are not limited to:

j. Development of Risk Evaluation and Mitigation Strategies or similar risk mitigation strategy proposals

k. Manufacturing/Testing facility plan to support clinical trial lots through commercial scale product supply, including consideration of capacity for surge manufacturing in the event of an influenza pandemic

Antiviral Clinical Evaluation Representative Activities may include but are not limited to:

Vaccine Advanced Research and Development Representative Activities may include but are not limited to:

Vaccine Process Development, Formulation, and Manufacturing Development Representative Activities may include but are not limited to:

j. Development of Risk Evaluation and Mitigation Strategies or similar risk mitigation strategy proposals

k. Manufacturing/Testing facility plan to support clinical trial lots through commercial scale product supply, including consideration of capacity for surge manufacturing in the event of an influenza pandemic

Vaccine Clinical Evaluation Representative Activities may include but are not limited to:

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.

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

Attachment 4: Reporting Requirements and Deliverables

Some reports and other deliverables are relevant to specific activities that may or may not be performed during the contract period of performance. The Offeror and the Government shall agree during final contract negotiations on which reports and other deliverables are relevant and shall be required as deliverables as determined in the negotiated SOW.

As part of the work to be performed under this BAA, the Contractor shall prepare and deliver the following reports throughout the period of performance. For all reports the Contractor shall submit two (2) paper copies and one (1) electronic copy to the Contracting Officer. Any documents should be submitted electronically in Microsoft Word, Microsoft Excel, Microsoft Project, and/or Adobe Acrobat PDF file formats.

The following reports may be required as deliverables during the period of performance of a contract, and are not elements of the Full Proposal submission.

Reports:

1. Integrated Product Development Plan Within fourteen days of contract award, an Integrated Product Development Plan (IPDP) or equivalent document may be required from the contractor, including all key program activities, milestones, and “go/no-go” decisions.

2. Technical Progress Reports The frequency of Technical Progress Reporting will be determined by the Government during negotiation of the contract. Typically, on the fifteenth (15) day of each month, the Contractor shall submit to the Contracting Officer and the Contracting Officer’s Representative (COR) a Technical Progress Report describing activities performed during the previous calendar month. The format and type of Technical Progress Report and Executive Summary will be provided by the COR. The Technical Progress Reports will include project timelines and summaries of product manufacturing, testing, and clinical evaluation activities. A Technical Progress Report will not be required for the period when the Final Report is due. The Contractor shall submit one copy of the Technical Progress Report electronically via e-mail. Any Technical Progress Report documents shall be submitted in Microsoft Word, Microsoft Excel, Microsoft Project, and/or Adobe Acrobat PDF file formats. The Contractor should inform the Contracting Officer and the COR in advance if the delivery of a Technical Progress Report will be delayed.

3. Final Report By the expiration date of the contract, the Contractor shall submit a comprehensive Final Report that shall detail, document, and summarize the results of the entire contract work. The report shall explain comprehensively the results achieved. A draft Final Report will be submitted to the Contracting Officer and COR for review and comment, after which the Final Report shall be submitted with one original, four copies, and an electronic file to the Contracting Officer and COR.

Additional reports and deliverables may be required in the final negotiated contract.

Meetings and Conferences:

The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Contracting Officer and COR. Such meetings may include, but are not limited to, all Contractors and subcontractors to discuss clinical manufacturing progress, product development, product assay development, scale-up manufacturing development, clinical sample assay development, preclinical/clinical study designs and regulatory issues, or other relevant activities; meetings with individual Contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program; and meeting with Government technical consultants to discuss technical data provided by the Contractor.

Monthly teleconferences between the Contractor and subcontractors and BARDA shall be held to review technical progress. BARDA reserves the right to request more frequent teleconferences and face-to-face meetings depending on the criticality and nature of the work being performed. Contractor will receive feedback from BARDA during the monthly teleconference regarding contract performance. The Contractor will have an opportunity to respond and provide recommendations / remediation plan during the execution of the contract.

The only contractual relationship shall be between the Government and the prime Contractor. No business obligation exists between the Government and any subcontractors unless a teaming arrangement is established.

Regulatory and Quality Management: