BARDABAA11100SOL00021.pdf

BARDA BAA-11-100-SOL-00021 Page 1

BARDA BAA-11-100-SOL-00021

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, Room G640, Washington, DC, 20201

Issuing Office: 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, Room G640, Washington, DC, 20201

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

Announcement Type and Date: Initial Announcement, June 20, 2011.

Eligible Applicants: This BAA is open to ALL responsible sources. Offerors may include single entities or teams from private sector organizations, Government laboratories, Federally Funded Research and Development Centers (FFRDCs), and academic institutions.

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 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, an ability to comply with the performance schedule, 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 (BARDA) is soliciting advanced research and development projects to improve available medical countermeasures to protect the US population from influenza pandemics.

BARDA anticipates that development activities supported under this BAA will improve the utility, availability and effectiveness of existing medical countermeasures (diagnostics and respiratory devices) and/or mature candidate medical countermeasures towards FDA clearance/approval.

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Table of Contents

Overview Information Table of Contents Introduction Pre-Proposal Conferences Part I: Development Areas of Interest

Area of Interest #1: Personal Protective Equipment (Mask & Respirators) and Full- Featured Continuous Ventilators for Influenza Infection and All-Hazards Area of Interest #2: Clinical Influenza Test Systems and Diagnostic Tools

Part II: Product Development and Technical Objectives Part III: Reporting Requirements and Deliverables Part IV: Proposal Preparation and Submission

Section 1: The Application Process Section 2: Stage 1 Quad Chart and White Paper Section 3: Quad Chart and White Paper Submission Section 4: Stage 2 Full Proposal Preparation

A. Volume I - Technical Proposal B. Volume I – Appendices C. Volume II – Cost Proposal D. Volume II – Cost Proposal Appendices E. Representation and Certifications F. Studies That Involve Human Subjects G. Animal Welfare H. Security Planning:

I. Intellectual Property:

J. Biographical Sketches:

K. Prohibition on the Use of Appropriated Funds for Lobbying Activities HHSAR 352.270-10 Anti-Lobbying (Jan 2006) L. Use of Select Agent M. Laboratory License Requirements N. Advanced Understandings

Section 5: Full Proposal Submission Section 6: General Information

Part V: Proposal Evaluation A. Evaluation Criteria B. Past Performance Information

Part VI: Special Instructions Part VII: Attachments

Attachment 1: Technology Readiness Level (TRL) Criteria Attachment 1A: Draft Technology Readiness Level (TRL) Definitions for Medical In- Vitro Diagnostic Devices Attachment 1B: Department of Defense Technology Readiness Assessment Deskbook

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Attachment 2: Full Proposal Volume II - Breakdown Of Proposed Estimated Cost (Plus Fee) And Labor Hours Attachment 3: Summary of Related Activities Attachment 4: Government Notice for Handling Proposals Attachment 5: Quad Chart and White Paper Format Template Attachment 6: Target Product Profile Template Attachment 7: BAA Instruction Language for Earned Value Management (EVM)

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BARDA BAA-11-100-SOL-00021

Introduction

This Broad Agency Announcement (BAA) sets forth research and 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 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 overall population. However, it is possible that future pandemics will feature morbidity and mortality rates comparable with historically 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 and diagnostics are essential to protect all segments of the civilian population. This BAA will support advanced development activities to improve candidate products and diagnostic tools and incorporate considerations of the challenging lifecycle requirements of these products before and during a pandemic (e.g.

shelf life, storage, distribution, and dispensing).

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 (Nov, 2005), the National Pandemic Influenza Implementation Plan (May, 2005), recommendations from the Public Health Emergency Medical Countermeasure Enterprise Review (Aug, 2010) and the President’s Council of Advisors on Science and Technology report on influenza vaccines manufacturing (Aug, 2010). The HHS Public Health Emergency Medical Countermeasures Enterprise Review emphasizes the need to improve medical countermeasure technologies and move towards a “nimble, flexible capacity to produce MCMs rapidly in the face of any attack or threat”.

This BAA is open to all responsible sources. Offerors may include single entities or teams from private sector organizations, Government laboratories, Federally Funded Research and Development Centers (FFRDCs), and academic institutions.

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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, as long as they are permitted 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, ability to comply with the performance schedule, 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.

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:

• Personal Protective Equipment and Full-Featured Continuous Ventilators for

Influenza Infection & All-Hazards

• Clinical Influenza Test Systems and Diagnostic Tools

Given the future availability of funds, this BAA may be expanded to incorporate development of other medical countermeasure products. Any such changes would be incorporated as BAA Amendments, and would be posted on http://www.fbo.gov.

Development and technical objectives are described in Part II, and efforts proposed by Offerors may include such activities as Non-Clinical Product Development, Manufacturing Process Development, Formulation, and Clinical Evaluation.

Offerors must identify in their Quad Chart and White Paper the current Technology Readiness Level (TRL) of their medical countermeasure product. See Attachment 1: Technology Readiness Level (TRL) Criteria. Two TRL criteria 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 product maturity.

Please note that all activities within a TRL level (or sublevel) must be completed to have achieved that TRL status.

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 Part IV. 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 submission deadlines: July 15, 2011, October 14, 2011 January 13, 2012 and April 13, 2012. Decision letters will be sent to Offerors within 90 days of submission or within 90 days after the submission deadline.

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In Stage 2, Offerors receiving a favorable evaluation will be asked to prepare a Full Proposal and submit to BARDA within 45 days depending on time and funding constraints.

Instructions for completing the Full Proposal are found in Part IV of this announcement. A request to submit a Full Proposal does not assure an award. The Government intends to make an award decision within 120 days after submission of Full Proposals.

The success of a product development program requires a relentless focus on the desired characteristics of the resulting medical countermeasure product. During Stage 2, in addition to the Full Proposal, Offerors are requested to provide a Target Product Profile. A template for a Target Product Profile is included in Attachment 1 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 is obtained. All Offerors are encouraged to submit a Target Product Profile for the proposed medical countermeasure, 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 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.

Offerors contemplating submitting Quad Charts, White Papers, and Full Proposals are strongly encouraged to contact the appropriate technical Point of Contact (POC) at BARDA (e-mail addresses are provided in Part I of this announcement). Offerors are advised that only a Contracting Officer may obligate the Government to any agreement involving expenditure of Government funds. Once a white paper or full proposal has been submitted, all communications must be conducted through the BARDA Contracting Officer (The Office of Acquisitions Management, Contract & Grants).

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

Quad Chart and White Papers and/or Full Proposals WILL NOT BE ACCEPTED after 3:00 PM (Eastern Standard Time) on September 13, 2011.

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.

BARDA reserves the right to fund all, some, or none of the proposals submitted. While award is anticipated to occur according to the stated schedule, Offerors that are not responsive to BARDA requests for information in a timely manner, will not be considered for an award.

BARDA reserves the right to award the contract instrument best suited to the nature of the development activities proposed and may award any appropriate contract type under the Federal Acquisition Regulation. BARDA may also elect to make awards in the form of grants and cooperative agreements, with the possibility of awarding Other Transactions (OT)

BARDA BAA-11-100-SOL-00021 Page 7 agreements in the future as appropriate, as authorized for BARDA under the Pandemic and All Hazards Preparedness Act (2006).

Multiple awards at various funding levels, base periods, and options are anticipated and are dependent upon the proposals’ scientific and technical merits, how well the proposals fit BARDA’s areas of interest, and available funding.

Special instructions will be advertised via the BAA as they become apparent. These additional instructions are tailored to specific topic areas and may have unique submittal dates. The information requested in these instructions should be used along with Part IV of the BAA to format and prepare the Technical and Business Proposals.

Anticipated funding for the program (not per contract or award) may range from $15-75M dollars subject to Congressional appropriations. 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.

All administrative inquires regarding this BAA shall be addressed to FLU-BAA@hhs.gov.

Technical questions shall be referred to the Point Of Contacts (POCs) shown following each development area of interest. Please include contact information with any inquiry.

This BAA is available on the following websites:

https://www.fbo.gov https://www.medicalcountermeasures.gov/ http://www.hhs.gov/aspr/barda/

This BAA is a continuously open announcement valid for the period from the date of issuance through June 20, 2012, unless announced otherwise. Amendments to this BAA will be posted to the websites listed above. Interested parties are encouraged to periodically check these websites for updates and amendments.

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Pre-Proposal Conferences

Note: Offerors are encouraged to attend the conference however, seating will be limited.

Pre-proposal Conference #1: July 13, 2011 1:00 PM – 4:00 PM for all development areas of interest.

Hubert H. Humphrey Building 1st Floor Auditorium 200 Independence Avenue S.W.

Washington, DC 20201

Please note the following regarding the pre-proposal conference:

1. Attendance is limited to a maximum of two (2) people per company. Email the names of your attendees and Development Area of Interest to FLU-BAA@hhs.gov by June 30, 2011. To ensure an equal distribution of attendees in each Development Area of Interest, registration for each section will be controlled and a wait-list established.

2. Enter the Humphrey Building at the Independence Avenue Street entrance.

3. Arrive 30 minutes early to allow time to clear security.

4. Bring your identification

5. The closest metro stop is Federal Center SW

6. Tape recorders and videos are prohibited.

7. Presentation material from the conference will be posted on FedBizOpps in an amendment to the BAA following the pre-proposal conference

NOTE: For those who are unable to attend, please use the following dial-in information:

(866) 880-0098 Passcode: 3458287#. Dial-in attendees will be muted.

Pre-proposal Conference #2: A second pre-proposal conference may be announced in a subsequent FedBizOps amendment to this BAA.

Questions from industry may be emailed to Flu-BAA@hhs.gov no later than June 30, 2011. Submitted questions will be address during the July 13, 2011 Pre-Proposal Conference.

Part I: Development Areas of Interest Through this solicitation, BARDA seeks to support development strategies in the following product development areas of interest. This section presents the influenza-related technical objectives that BARDA seeks to achieve through this BAA. Each Offeror shall also review Part II: Research and Technical Objectives.

Area of Interest #1: Personal Protective Equipment (Mask & Respirators) and Full- Featured Continuous Ventilators 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

BARDA BAA-11-100-SOL-00021 Page 9 that TRL. The Technology Readiness Level ranking criteria can be found in Attachment 1B of this solicitation.

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-hazard events.

1.2 Development of improved full-featured continuous ventilators. Advanced development of new or improved ventilator to provide life support in clinical and non-clinical environments for severe respiratory conditions resulting from influenza infections or all-hazards events. Ideal ventilators would support neonate to adult populations and be capable of operation by unskilled or minimally trained care providers with considerations for ease of stockpiling/maintenance, accommodation/provision of accessories typically used in ventilatory standard of care, low cost per unit, and domestic surge capacity.

Technical inquiries can be directed to FLU-BAA-MITIGATE@HHS.GOV

Area of Interest #2: Clinical Influenza Test Systems and Diagnostic Tools 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 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 Technology Readiness Level ranking criteria are provided in Attachment 1A & 1B of this solicitation; either criterion can be used for evaluation. Design, manufacturing, and assembly of reagents and system components must be consistent with U.S. Quality Systems Regulations (21 CFR Part 820).

Offerors should indicate an understanding of CLIA requirements for influenza diagnostics.

2.1 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 with beneficial clinical and public health impact. Critical technology component should be at a maturity level equal to or greater than TRL 6.

2.2 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, and 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.

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

2.4 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.

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2.5 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.

2.6 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.

2.7 Development and characterization of stable diagnostic reagents or reference material and controls for applications 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. Critical technology component should be at a maturity level equal to or greater than TRL 8.

Technical inquiries can be directed to FLU-BAA-DIAGNOSTIC@HHS.GOV

Part II: Product Development and Technical Objectives This information is provided to assist and guide Offerors in preparing their Statement of Work (SOW). Offerors shall submit a SOW in their proposal that addresses these topics as appropriate, and shall provide as much detail as may be necessary to fully explain the proposed technical approach or method. The topics listed below exemplify some of the typical developmental activities in the areas of clinical research, manufacturing, clinical evaluation, project management, and regulatory strategy contained in a typical drug, biologic or device development effort.

Proposal preparation and submission instructions are contained in Part IV.

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:

• 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.

• Field evaluations of PPEs to filter influenza viruses and other respiratory pathogens.

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• 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 effectivenss of these devices in relevant environments.

• Evaluate diagnostic value of test methods for informing clinical and public health management 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.

Influenza Test System 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 reagents, components, and materials.

b. Internal and External Validation Studies:

• Assessments of specimen processing methods and specimen target stability using modified or new collection and transport materials.

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

• Optimize new or modified assays on existing platforms.

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

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

c. Manufacturing:

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

• Maintain appropriate quality assurance with processes, procedures, and documentation consistent with design controls (as applicable), Quality

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Systems, and relevant standards (e.g., deviation and risk management strategies).

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

d. Other Product Development Activities:

• 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.

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

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

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

• 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.

• 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.

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

B. Management Approach:

1. Representative Activities for the Integrated Product Development Plan (IPDP) must include as applicable, but are not limited to:

a. A detailed project plan that indicates the activities that the Offeror is proposing to perform under contract funding in both the base period and option period(s), including all of the functional areas of development listed below.

b. A detailed description of the experimental design, including the rationale for experimental approaches, and a description of alternative approaches to be employed if these methods do not achieve the defined goals.

c. Key steps in the product development pathway that represent opportunities for “go/no go” decisions for advancing to the next stage of the Integrated Product Development Plan (IPDP).

d. The qualitative and quantitative criteria and accompanying data that will be used to assess the scientific merit and technical feasibility of each stage of product development.

e. 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.

f. A listing and resumes of key personnel (including proposed consultants) who possess the necessary education, training, and experience to successfully perform the work identified in the technical proposal.

g. A staffing plan that indicates personnel resources (in-house and contracted) and the percentage of time to be dedicated to perform the work.

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h. A clear and comprehensive regulatory master plan that identifies the critical path integrating risk evaluation and mitigation at all development stages (non-clinical testing, clinical testing, and manufacturing activities) using the most current available information, including documented and time-relevant consultation with FDA.

i. A plan for additional studies to support future filing for FDA-approval/clearance.

j. Summary of any prior communication with the FDA relevant to product development, including a summary of audits and inspections.

k. A tentative schedule of anticipated regulatory milestones.

l. A plan for potential use of the product under Emergency Use Authorization (EUA).

(http://www.cdc.gov/eid/content/13/7/1046.htm)

m. A clear and consistent work breakdown structure (WBS) that may include data at the cost account level, at the work package level, or at a lower level if there is significant complexity and risk associated with the task.

n. An approach for tracking milestones, costs, risks, subcontractor effort (if applicable), and deliverables, and any proposed internal procedures for assuring timely responses to the Government’s needs.

o. An approach for performance measurement that shall include establishing an initial plan; defining measurable parameters; defining how these parameters relate to cost and schedule impacts; presenting a detailed schedule that includes a critical path for the project; and a description of the cost-accounting system based on budget estimates to monitor all costs related to the contract award for both prime- and sub-contractors on a real-time basis.

Within fourteen (14) days of the effective date of the BAA award, the Offeror shall submit an updated IPDP which shall be approved by the Project Officer and the Contracting Officer prior to initiation of any activities related to their implementation.

During the course of contract performance, in response to a need to change the IPDP, the Offeror shall submit a Deviation Report. This report shall include a requested change in the previously approved IPDP and associated timelines, and shall include:

a. Discussion of the justification/rationale for the proposed change.

b. Options for addressing the needed changes, including a cost-benefit analysis of each option.

c. Recommendation that includes a full analysis of the effect of the change on the entire product development program, timelines, and budget.

The Offeror shall carry out activities within the contract SOW only as requested and approved by the Contracting Officer, and may not conduct work on the contract without prior approval from the Contracting Officer, including the initiation of any work that deviates from the approved

IPDP.

Offeror shall comply with all applicable regulatory requirements. Filing of regulatory submissions shall be made to the relevant FDA center.

The Offeror shall use Earned Value Management to monitor the progress of their project.

Additional instructions can be found in Attachment 1.

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2. Target Product Profile (TPP): In their proposal, Offerors shall include a draft TPP for their proposed candidate medical device or system objective. Offerors should use the template in Attachment 6 to develop the TPP, and should include the following elements:

a. The intended use or indication of the proposed medical countermeasure.

b. The intended product profile (strength, quality, purity and identity) noting the performance specifications and features of the medical countermeasure that provide benefit.

c. A description of the medical countermeasure as it is currently configured.

d. A description of the manufacturing process or mode of distribution including expected formulation (configuration) of the final product.

e. A description and developmental status of the assays or methods for product release which will be used for characterization, strength, identity, and purity, as well as any needed assays for product activity and efficacy.

f. Any discussions with appropriate FDA reviewers that are relevant to development activities for the proposed medical countermeasure, including plans for generating data to support an Investigational New Drug (IND), Biologics License Application (BLA) or New Drug Application (NDA), Investigational Device Exemption (IDE), Premarket Approval (PMA) and/or 510(k) application; summary of any prior, time-relevant communication with FDA relevant to the product development for the indication noted; and summary of audits and inspections relative to the current development or proposed manufacturing of the intended product (including key subcontractors).

3. Representative Activities for Contractor-Provided Facilities, Infrastructure and other Resources must include as applicable but are not limited to:

a. Current facility design, including quality control labs for testing & release, laboratory areas supporting formulation and assay development, manufacturing process flow, and analytical studies.

b. Major equipment and layout (preliminary piping and instrumentation drawing).

c. Manufacturing capacity expansion plans to match the proposed manufacturing scale up.

d. Overview of the management of Quality Systems at the facility.

e. List of capabilities for clinical activities conducted in-house and at contract research organizations.

f. Qualified animal facilities where GLP studies would be conducted and appropriate certifications for humane care and use of vertebrate animals.

Detailed instructions on proposal preparation and submission are contained in Part IV.

g. The handling, storing and shipping of potentially dangerous biological and chemical agents, including Select Agents, under biosafety levels required for working with the particular biological agents under study. Detailed instructions on proposal preparation and submission are contained in Part IV.

h. Validation master plan for key equipment, analytical methods and manufacturing process.

Part III: 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 Contractor, the Project Officer and the Contracting Officer shall agree in the final contract negotiations on which reports and other

BARDA BAA-11-100-SOL-00021 Page 15 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 to the Contracting Officer one (1) electronic copy and one (1) paper copy.

Reports:

1. Technical Progress Reports

The frequency of Technical Progress Reporting will be determined by the Contracting Officer and Project Officer during negotiations of the contract. Typically, on the fifteenth (15) day of each month for the previous calendar month, the contractor shall submit to the Contracting Officer. The format and type of Technical Progress Report and Executive Summary will be provided by the Project Officer. Each Technical Progress Report will include project timelines and milestone summaries of all activities funded under the contract, such as product manufacturing, testing, and clinical evaluation. 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 files. Such reports shall include the following specific information:

a. Title page containing: Technical Progress Report, the contract number and title, the period of performance or milestone being reported, the contractor’s name, address, and other contact information, the author(s), and the date of submission;

b. Introduction/Background: An introduction covering the purpose and scope of the contract effort;

c. Progress: The report shall detail, document and summarize the results of work performed, test results, milestones achieved during the period covered and cumulative milestones achieved. Also to be included is a summary of work planned for the next two (2) reporting periods on a rolling basis;

d. Issues: Issues resolved, new issues and outstanding issues are enumerated with options and recommendation for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if progress activity is delinquent, then what corrective steps are planned. Revised timelines are provided.

e. Invoices: Summary of any invoices submitted during the reporting period.

f. Action Items: Summary table of activities or tasks to be accomplished by certain date and by whom.

g. Distribution list: A list of persons receiving the Technical Report

h. Attachments: Results on the project are provided as attachments

2. The Executive Summary, which shall accompany each Technical Progress Report, will be provided in Microsoft Power Point format and shall include the following:

a. Title page containing Executive Title, the contract number and title, the period of performance or milestone being reported, the contractor’s name and the date of submission;

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b. Project Progress presented as milestone events, test results, tasks, and other activities achieved during the reporting period as talking point bullets;

c. Project issues presented headings and each item as a talking point bullet.

3. The Earned Value Management Report shall accompany each Technical Progress Report.

4. 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 all work performed under the entire contract. The report shall comprehensively explain the results achieved, and clearly document and justify any instance in which desired results were not achieved. A draft Final Report will be submitted to the Project Officer and Contracting Officer for review and comment. Once all requested changes are made, the Final Report shall be submitted to the Contracting Officer as one original paper copy, four additional paper copies, and an electronic copy.

Meetings and Conferences:

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

Monthly teleconferences between the Contractor 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 will be expected to develop remediation plans based on BARDA recommendations and the progress of the project during the execution of the contract.

Regulatory and Quality Management:

FDA Submissions and meetings:

a. The contractor shall forward the initial draft minutes and final draft minutes of any formal meeting with the FDA to BARDA.

b. The contractor shall forward the final draft minutes of any informal meeting with the FDA to BARDA.

c. The contractor shall inform BARDA of the dates and times of any meeting with the FDA and make arrangements for appropriate BARDA staff to attend FDA meetings as appropriate.

d. The contractor shall provide BARDA the opportunity to review and comment upon any documents to be submitted to the FDA. The contractor shall provide BARDA with ten (10) business days in which to review and provide comments back to the contractor.

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e. The contractor shall forward Standard Operating Procedures upon request from the Project Officer and/or Contracting Officer.

f. The contractor shall provide upon request animal study and/or other technology packages developed under this contract. Packages shall include complete protocols and critical reagents for animal models developed and/or improved with contract funding.

g. The contractor shall provide upon request raw data and/or specific analysis of data generated using USG funds.

h. The contractor shall maintain and provide on request regulatory and legal strategies related to the scope of work. Identify any federal, state or local requirements pertaining to patient safety and welfare.

i. The contractor shall maintain appropriate quality assurance with respect to processes, procedures, and documentation.

Audits / Site Visits:

FDA Audits Within thirty (30) calendar days of an FDA audit of Contractor or subcontractor facilities, the Contractor shall provide copies of the audit findings, final report, and a plan for addressing areas of nonconformance to FDA regulations and guidance for GLP, GMP or GCP guidelines as identified in the final audit report.

BARDA Audits The United States Government (USG) reserves the right to conduct an audit of the Contractor with 48 hours notice. The USG reserves the right to accompany the Contractor on routine and for-cause site-visits/audits of subcontractors. At the discretion of the USG and independent of testing conducted by the Contractor, BARDA reserves the right to conduct site visits/audits and collect samples of product held by the Contractor and subcontractors.

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Part IV: Proposal Preparation and Submission

Section 1: The Application Process The application process occurs in two stages as follows:

Stage 1: Complete a cover sheet, Quad Chart, and White Paper in accordance with the preparation guidance below. 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. Offerors whose Quad Chart and White Paper receive a favorable evaluation will be invited to submit a Full Proposal. Offerors whose Quad Chart and White Paper did not receive a favorable evaluation will be notified by email.

Stage 2: Offerors who are invited to submit Full Proposals must do so in accordance with the instructions provided below. Full Proposals will be evaluated against the Evaluation Factors as described in Part V. Proposals that do not conform to the requirements outlined herein will not be reviewed or considered for further action.

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

July 15th, 2011, October 14, 2011, January 13th, 2012 and April 13th, 2012.

Receipt confirmation within 1 week.

Decision within 90 days

Stage 2: Full Proposal Within 45 days of Invitation Receipt confirmation within 1 week

Source Selection Notification (pending availability of funds)

Within 120 days of receipt of Full Proposal

Section 2: Stage 1 Quad Chart and White Paper Interested Offerors shall submit a Quad Chart, a White Paper, and an addendum. The Quad Chart is not to exceed one (1) page, the White Paper is not to exceed ten (10) pages, and the addendum is not to exceed two (2) pages. If a submission exceeds these page limitations, only those pages that fall within the page limits will be reviewed. Combine all files into a single searchable PDF file before submitting.

Quad Chart Format: All Quad Charts should include the information indicated on the sample template located in Attachment 6. Quad Charts should be laid out in landscape format.

1. Heading: Title; Research Area Addressed; Offeror point of contact; Company Name

2. Upper left: Objective; description of effort

3. Lower left: Benefits of proposed technology; challenges; maturity of technology research area addressed as indicated by TRL (see Attachment 1)

4. Upper right: Picture or graphic

5. Lower Right: Milestones; costs; period of performance

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White Paper Technical Information:

1. In general, the white paper should provide a brief technical discussion of the

Offeror’s objective, approach, level of effort, and the nature and extent of the anticipated results. Specifically, the white paper should include, at a minimum, the following core elements:

a. brief discussion on how the proposed countermeasure aligns with the objectives of the National Strategy for Pandemic Influenza, the HHS Pandemic Influenza Implementation Plan, and other federal government strategies and plans.

b. a brief description of the maturity level of the proposed countermeasure using the appropriate Technology Readiness Level (TRL) criteria provided in Attachment 1.

c. a clear, concise development plan that includes all non-clinical, clinical, manufacturing, and regulatory activities required for the proposed countermeasure.

d. a high-level Gantt chart showing an overview of the proposed activities and timelines.

e. a brief description of the Offeror’s intellectual property ownership of the proposed countermeasure.

f. overview of Offeror’s capabilities and experience (past and current) as they relate to the proposed program.

2. The cost portion of the White Paper shall contain a brief cost estimate including all the component parts of the proposal.

3. A two-page addendum shall include biographical sketches of the key personnel who will perform the research, highlighting their qualifications and experience.

Restrictive markings on White Papers: Classification: All Quad Chart and White Paper submissions must be UNCLASSIFIED. Proposal submissions will be protected from unauthorized disclosure in accordance with FAR Subpart 15.207, HHS regulations, and all applicable laws. Offerors that include data in their proposal that they do not want disclosed shall mark their proposal in accordance with the instructions contained FAR 52.215-1(e) Restrictions on disclosure and use of data. Please note that any white paper submitted under this solicitation may be shared with other government agencies for non-BARDA funding considerations.

Section 3: Quad Chart and White Paper Submission White Papers must be emailed to the following email address:

FLU-BAA@hhs.gov

Include “BAA BARDA 11-100-SOL-00021 QUAD CHART & WHITE PAPER for Research Area #_” in the email subject line. White Papers must be submitted in the following format but do not require any special forms:

• Single PDF formatted file as an email attachment

• Page Size: 8 ½ x 11 inches

• Page limit: 10 pages• Margins – 1 inch

• Spacing – single

• Font – Arial, 11 point

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Electronic files should not exceed 2 Megabytes of storage space. Movie and sound file attachments, URL links, or other additional files will not be accepted.

Notification to Offerors: All…