CBRN BAA-12-100-SOL-00011 .pdf

BARDA CBRN BAA-12-100-SOL-00011

Overview Information

Agency Name: Department of Health and Human Services, Office of the Secretary, Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority 330 Independence Avenue, SW, Rm 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 Research and Development of Chemical, Biological, Radiological, and Nuclear Medical Countermeasures

Announcement Type and Date:

Broad Agency Announcement renewal announcement, June 08, 2012 as BARDA CBRN

BAA-12-100-SOL-00011.

Initial Announcement as BARDA CBRN BAA-09-34, issued March 4, 2009 – expired March 3, 2010.

Renewed March 4, 2010 as BARDA CBRN BAA-10-100-SOL-00012, expired March 3, 2011.

Renewed March 4, 2011 as BARDA CBRN BAA-11-100-SOL-00009, expired March 3, 2012.

Eligible Applicants: This BAA is open to ALL responsible sources. Offerors may include single entities or teams from private sector organizations, Government laboratories, and academic institutions.

To be eligible for award, a prospective recipient must meet certain minimum standards pertaining to financial resources, ability to comply with the performance schedule, prior record of performance, integrity, organization, experience, operational controls, technical controls, technical skills, facilities, and equipment.

Federally Funded Research and Development Centers (FFRDCs) and Government entities (Government/National laboratories, military educational institutions, etc.) are subject to applicable direct competition limitations and cannot propose to this BAA in any capacity unless they address the following conditions. FFRDCs must clearly demonstrate that the proposed work is not otherwise available from the private sector AND must also provide a letter on letterhead from their sponsoring organization citing the specific authority establishing their eligibility to propose to government solicitations and compete with industry, and compliance with the associated FFRDC sponsor agreement and terms and conditions. This information is required for FFRDCs proposing to be prime or subcontractors. Government entities must clearly demonstrate that the work is not otherwise available from the private sector and provide written documentation citing the specific statutory authority (as well as, where relevant, contractual authority) establishing their ability to propose to Government solicitations. Specific supporting regulatory guidance, together with evidence of agency approval will be required to fully establish eligibility. BARDA will consider eligibility submissions on a case-by-case basis;

however, the burden to prove eligibility for all team members rests solely with the Proposer.

Historically Black Colleges and Universities (HBCU), Minority Institutions (MI), Small Business concerns, Small Disadvantaged Business concerns, Women-Owned Small 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 for chemical, biological, radiological, and nuclear agents that threaten the U.S. civilian population.

BARDA anticipates that research and development activities awarded under this BAA will serve to advance candidate medical countermeasures towards FDA licensure/approval and consideration for acquisition.

TABLE OF CONTENTS

Overview Information

TABLE OF CONTENTS

Pre-Proposal Conference:

Part I: Research Areas of Interest

Area of Interest #1: Vaccines Area of Interest #2: Antitoxins and Therapeutics Area of Interest #3: Antimicrobial Drugs Area of Interest #4: Radiological/Nuclear Threat Medical Countermeasures .. 12 Area of Interest #5: Chemical Threat Medical Countermeasures:

Area of Interest #6: Clinical Diagnostics Tools:

Part II: Research 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 Preparation Section 3: Quad Chart and White Paper Submission Section 4: Stage 2 Full Proposal Preparation Section 5: Full Proposal Submission Section 6: General Information

Part V: Proposal Evaluation Part VI: Special Instructions Part VII: Attachments

Attachment 1: Technology Readiness Level (TRL) Definitions for Medical In-Vitro Diagnostic Devices……………………………………………………………… ... 51 Attachment 2: Volume II - Breakdown Of Proposed Estimated Cost (Plus Fee) And Labor Hours Attachment 3: Security Template Attachment 4: Summary of Related Activities Attachment 5: Government Notice for Handling Proposals Attachment 6: Quad Chart and White Paper Format Template Attachment 7: Target Product Profile Template Attachment 8: Additional Requirement Information…………………………… 71

INTRODUCTION

This Broad Agency Announcement (BAA), which sets forth research areas of interest for the Biomedical Advanced Research and Development Authority (BARDA), is issued under paragraph 6.102(d)(2) of the Federal Acquisition Regulation (FAR). Proposals selected for award are considered to be the result of full and open competition and in full compliance with the "The Competition in Contracting Act of 1984" 41 U.S.C. § 251 et seq.

BARDA, the lead federal agency for supporting advanced development of medical countermeasures (MCM) to address CBRN threats for the civilian population, is located within the Office of the Assistant Secretary for Preparedness and Response (ASPR), U.S.

Department of Health and Human Services (HHS). BARDA is soliciting proposals for the advanced research and development of MCM for chemical, biological, radiological, and nuclear (CBRN) agents that threaten the U.S. civilian population. The continuing threat of terrorism underscores the compelling need to develop new and improved MCM for protecting all segments of the civilian population. This BAA will support the development of candidate products and diagnostic tools to meet the challenging requirements of CBRN MCM (e.g. post-exposure efficacy, extended shelf life, storage, distribution, and dispensing). Contracts resulting from this BAA may also benefit from multiple core services that BARDA provides already, and will provide, in the future. These core services include an animal study network, flexible manufacturing facilities, and technical expertise in development, manufacturing, regulatory affairs, quality systems, and clinical studies

BARDA’s priorities are aligned with the preparedness mission of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), as articulated in the PHEMCE Strategy and Implementation Plan of 2007 and the upcoming plan this year (http://www.hhs.gov/aspr/barda/phemce/index.html). Specifically, HHS has generally adopted a strategy of developing and acquiring medical countermeasures for post-event response to CBRN threats. Preventive measures are appropriate only for threats of such potential catastrophic consequence that a pre-event strategy will be examined in order to reduce vulnerability and mitigate post-event consequences. Currently, no pre-event MCM strategies are deemed necessary and feasible at this time for the U.S. civilian population. Therapeutics and diagnostics or the use of post-event prophylaxis will be the preferred strategy for all other threats. Priority will be placed on medical countermeasures that focus on post-event prophylaxis or post-exposure treatment. Some CBRN programs are reaching maturity and the intended goal and will receive less emphasis. More emphasis will be placed upon product candidates that have multi-purpose indications (i.e. CBRN usage and commercial indication for public health needs). Additional focus will be placed on supporting the development of medical countermeasures suitable for use in special populations such as children, pregnant women, the elderly, and persons with compromised immune systems, prioritizing and supporting projects that provide benefits to all populations where possible and exploring focused development projects or studies where necessary. To that end, BARDA supports the advanced research/development and acquisition of MCM such as vaccines, therapeutics, and diagnostics.

For additional requirements information, please refer to Attachment 8.

The Pandemic and All Hazard Preparedness Act Pub. L. No. 109-417, 42 U.S.C. § 241 et seq.

(PAHPA; http://www.hhs.gov/aspr/opsp/pahpa/index.html) 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 http://www.hhs.gov/aspr/barda/phemce/index.html http://www.hhs.gov/aspr/opsp/pahpa/index.html strategic initiatives, such as rapid diagnostics, broad spectrum antimicrobials, and vaccine manufacturing technologies (See 42 U.S.C. 247d-7(c)(2)(B)).

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

Research Areas of Interest:

1. Vaccines

2. Antitoxins and Therapeutics

3. Antimicrobial Drugs

4. Radiological and Nuclear Threat Countermeasures

5. Chemical Threat Countermeasures

6. Diagnostics

Research and technical objectives are described in Part II and efforts proposed by Offerors may include activities in Non-Clinical Research and Development, Process Development, Formulation, and Manufacturing Development, and Clinical Evaluation. For drug and biologic medical countermeasure development efforts, Offerors shall propose a Statement Of Work (SOW) preferred to be consistent with activities between Integrated Technology Readiness Levels (TRLs) 6 to 7 (see https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx). For Diagnostic, Offerors shall propose a SOW consistent with activities at TRLs 4 or greater (refer to TRLs in Attachment 1). For CRN (Research Areas 4 and 5), Offerors shall propose a SOW that is consistent with activities occurring at TRL 3 or greater (see https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx). 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, and may be submitted at any time up to the closing date of the BAA. Brochures or other descriptions of general organizational or individual capabilities will not be accepted. Acknowledgement of receipt (electronic) will be made within one week.

For areas 1, 2, 3, and 6 there are four submission cut-off dates: September 1, 2012, December 1, 2012, March 1, 2013, and June 07, 2013 (4:30PM EST on each date). Decision letters to Offerors will be sent within 90 calendar days after the submission deadline.

Area 4 and Area 5 will remain open for continuous submissions, subject to this BAA’s expiration date, June 07, 2013. Decision letters to Offerors will be sent within 90 calendar days of submission.

In Stage 2, Offerors receiving a favorable evaluation will be asked to prepare a Full Proposal and submit to BARDA within 75 calendar 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. There are no specified funding limitations identified for proposals submitted under this BAA. The budget shall https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx be commensurate with the nature and complexity of the proposed research. The Government intends to make an award decision within 180 days after submission of Full Proposals.

Offerors contemplating submitting Quad Charts, White Papers, and Full Proposals are strongly encouraged to contact the appropriate technical Point of Contact (POC) at BARDA (see names and e-mail addresses listed immediately after each research area of interest). Offerors are advised that only a Contracting Officer may obligate the Government to any agreement involving expenditure of Government funds. Once a white paper or full proposal has been submitted, all communications must be through the BARDA Contracting Office (The Office of Acquisitions Management, Contracts & Grants).

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

Quad Chart and White Papers and / or Full Proposals WILL NOT BE ACCEPTED after 4:30 PM (Eastern Standard Time) on 07 June 2013.

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.

ASPR 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, defined as meeting government deadlines established and communicated with the 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. ASPR may also elect to make awards in the form of grants and cooperative agreements, with the possibility of awarding Other Transactions (OT) agreements.

Multiple awards of various values 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 a specific area of interest and may have a unique submittal date. 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.

Offerors should follow the instructions in Part IV of the BAA, and include the information requested therein. Please see Part VI for updated Special Instructions associated with this renewal.

Anticipated funding for the program (not per contract or award) may range from $2M to $415M dollars subject to congressional appropriations. This funding profile is an estimate only and will not be a contractual obligation for funding. All funding is subject to change due to government discretion and availability.

All administrative inquires regarding this BAA shall be addressed to CBRNBAA12.os@hhs.gov. Technical questions shall be referred to the Point Of Contacts (POCs) shown following each research area of interest. These POC’s are located below, in “Part I: Research Areas of Interest.” When an inquiry is made, please include all pertinent contact information.

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 07 June 2013, unless announced otherwise. Amendments to this BAA will be posted to the websites listed above when they occur. Interested parties are encouraged to periodically check these websites for updates and amendments.

mailto:CBRNBAA12.os@hhs.gov https://www.fbo.gov/ https://www.medicalcountermeasures.gov/ http://www.phe.gov/

Pre-Proposal Conference:

Note: Offerors are encouraged to attend the conference. However, the conference will have limited seating.

The conference will provide a short presentation of the requirements for each BAA, followed by scheduled individual meetings between attendees and a Project Officer for an Area of Interest.

Contracts staff and a representative from the Office of Small and Disadvantaged Business Utilization (OSDBU) will also be present to answer any questions about the BAA process. In addition, the conference will provide a unique opportunity to interact with others in the field.

Pre-proposal Conference: July 16, 2012 2:00 – 4:00PM EDT, for all research areas of interest.

200 Independence Avenue S.W.

Hubert H. Humphrey Building, Great Hall Washington, DC 20201

REGISTRATION

1. To register for the conference, please email the name of your company, as well as the names and *citizenship of registrants to AMCG-Opportunities@hhs.gov by 3:00 PM EDT Thursday, July 12, 2012.

2. Registration is limited to the maximum room occupancy, and may be suspended without prior notice. Companies may not register for multiple BAAs. However, information about all BAAs will be available to every attendee.

3. When registering, please indicate your primary and secondary area of interest and the appropriate BAA. We will assign you a 5 minute meeting with Program staff. Every effort will be made to accommodate everyone’s first choice; depending upon the number of registrants, a second meeting may be assigned. Meeting assignments will be provided upon arrival at the conference. If, after registering, you find that you must cancel, please let us know so that we can open up your meeting slot(s) to other attendees.

Please note the following regarding the pre-proposal conference:

• Enter the Humphrey Building at the Independence Avenue Street entrance and register with the guard at the front desk to receive a visitor pass.

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

• Bring your identification (photo identification).

• The closest metro stop is Federal Center SW, serviced by the Blue and Orange

Metrorail lines. At the top of the escalator turn left. The Humphrey Building is two blocks ahead on the right at the corner of 3rd St., SW and Independence Avenue, SW.

• At this time, attendance is limited to one (1) representative per company. For domestic participants, please email the name of your attendee to AMCG-Opportunities@hhs.gov by July 12, 2012. *For international participants, please email the name of your attendee to AMCG-Opportunities@hhs.gov by June 28, 2012.

• Tape recorders and videos are prohibited.

• 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:

Domestic Line: 888-677-3402 International: 1-517-268-4531 Participant code #: 14961

* Be advised that in order to obtain security clearance, advanced notification must be provided by all attendees who are not United States citizens. This includes residents holding Green Cards.

Notification must be received no later than June 28, 2012. You will be advised what information we need (passport, visa information, etc.) when you register.

Part I: Research Areas of Interest

Through this solicitation, ASPR seeks to support advanced research and development strategies in the following research areas of interest. Offeror shall review Part II: Research and Technical Objectives. This section presents the CBRN-related technical objectives that BARDA seeks to achieve through this BAA.

Area of Interest #1: Vaccines

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

• Fewer doses to protection

• Faster protective immune response

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

The proposed vaccine candidate must have demonstrated immunogenic equivalence to AVA in a non-clinical or clinical study with a minimum of 12 months stability (as measured by acceptable stability indicating assays) prior to white paper submission.

1.2 Programs to expand availability of licensed anthrax and smallpox vaccines for at risk populations, e.g. pediatric populations.

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

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

Area of Interest #2: Antitoxins and Therapeutics

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

2.2 Development of novel formulations of anthrax antitoxins.

2.3 Development of antibody treatments and other therapeutic biologics for viral hemorrhagic fevers viruses.

Technical Point of Contact: Dr. Stephen Morris; stephen.morris@hhs.gov

Area of Interest #3: Antimicrobial Drugs

The page limit for submissions in this area of interest may differ from other areas – all other specifications in Part IV: Proposal Preparation and Submission, Section 2: Stage 1 Quad Chart and White Paper Preparation apply. Initial submission is limited to: a cover page; a one-page quad chart; a one-page integrated product development timeline / task overview;

a White Paper not to exceed ten (10) pages and an addendum (not to exceed two (2) pages).

mailto:eric.espeland@hhs.gov mailto:stephen.morris@hhs.gov

In accordance with the Pandemic and All-Hazards Preparedness Act of 2006 (PAHPA), BARDA has the responsibility to ensure that the United States has a sufficient supply of vaccines and drugs to respond to public health emergencies caused by pandemic influenza, emerging infection diseases, and chemical, biological, and radiological and nuclear threats.

BARDA recognizes the dual utility of antimicrobials for the treatment and prevention of diseases caused by bacterial and viral threat agents, and clinically relevant emerging and drug resistant pathogens. Therefore, BARDA is actively seeking to support product development that builds synergy between threat agent and non-biodefense applications to maximize return on research investment.

The scope of this area of interest permits the following:

• Clinical studies to support non-biodefense indications.

• Additional work (e.g. manufacturing methodology development, assay development and validation) to support non-biodefense indications.

While non-biodefense studies may be supported, the pursuit of indications for biological threat agents is mandatory to be considered for award. Furthermore, the demonstration that any proposed, non-biodefense activities support ultimate readiness for biodefense (e.g. clinical safety data, manufacturing process improvement, etc.) will improve the competitiveness of proposals.

3.1 Development of novel small molecule antiviral candidates with activity against one or more biodefense threat agents (Ebola, Marburg, and Variola viruses).

3.2 Development and testing of antibiotics that are in advanced development (Phase I clinical trial ongoing or completed) for post-exposure prophylaxis (PEP) and treatment efficacy against multiple biodefense threat agents (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei). Minimum inhibitory concentration (MIC) data for multiple strains of multiple threat agent bacterial species is required; larger data sets (e.g. MIC90 calculations) will strengthen the proposal.

The strongest proposals will present data from relevant aerosol challenge animal models.

For mouse and non-human primates (NHPs), PEP is defined as administration of the candidate antibiotic a minimum of 24 hours post-exposure. For murine studies, treatment (delayed dosing) is defined as administration of the antibiotic 42 hours post-exposure. For NHP studies, treatment is defined as the administration of the antibiotic following an alteration in a physiologically relevant indicator (trigger) that is strongly correlated with the development of illness (e.g. fever, blood pressure, heart rate, positive blood culture or PCR positive, etc). Irrespective of the trigger for treatment used, all animals tested must be screened for a positive blood culture.

A product that has a greater degree of innovation compared to currently marketed antibiotics, therefore demonstrating a degree of innovation and potential to offer a revolutionary increase in capability will be viewed favorably.

Offerors may also strengthen a proposal by presenting a compound that is more clinically advanced (i.e. in Phase II or III studies) for a non-biodefense indication. Any proposed program must demonstrate a clear commitment to a comprehensive and technically realistic biodefense program.

Additional information is available at the following website www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx

Technical Point of Contact: Dr. Joseph Larsen; joseph.larsen@hhs.gov

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

4.1 Development of mitigators or treatments for subsyndromes associated with Acute Radiation Syndrome (ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE), arising from exposure to ionizing radiation. Treatments that have efficacy when administered after 24 hours post irradiation are of particular interest. Subsyndromes of interest include:

Neutropenia Thrombocytopenia Gastrointestinal Skin (Cutaneous) Lung (Pulmonary) Kidney (Renal) Brain (central nervous system)

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

4.2 Development of Decorporation agents (isotopes of interest: Co-60, Cs-137, U-235/238, Pu- 238/239, Sr-90, Am-241, Po-210, other transuranics) or new formulations of existing countermeasures (e.g., improved ease of administration).

Note: Special Instructions apply to the review cycle for this research area of interest. Please refer to Part VI for additional information

Technical Point of Contact: Dr. Ronald G. Manning; ronald.manning@hhs.gov

Area of Interest #5: Chemical Threat Medical Countermeasures:

Area of interest #5 includes medical countermeasures that protect the civilian population from the acute health effects of chemical threats, are easy to administer and rapidly effective as post-exposure therapies. The medical countermeasures should also be safe and effective in the entire population, including infants, children, adolescents, elderly, pregnant women and immunocompromised individuals. Specific areas of interest within Chemical Threat Medical Countermeasures include:

5.1 Nerve Agents:

5.1.1 Development of medical countermeasures (MCM) such as an improved anticonvulsant to replace or supplement diazepam, (faster acting after intramuscular administration; better efficacy, particularly after seizures are established; better efficacy in children).

http://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx mailto:joseph.larsen@hhs.gov mailto:ronald.manning@hhs.gov

5.1.2 Development of a neuroprotectant to prevent and treat hypoxic and/or excitotoxic brain damage.

5.1.3 Development of an improved acetylcholinesterase reactivator to replace pralidoxime chloride (e.g., broad spectrum; centrally acting)

5.1.4 Development of an improved anticholinergic to supplement atropine (longer acting and centrally acting).

5.1.5 Development of new formulations of existing antidotes (more easily administered;

faster acting).

5.1.6 Development of easily administered and rapidly effective countermeasures that can be used by first responders dealing with large numbers of exposed individuals. Ease of administration in mass casualty situations should take into account the practical limits of injected medications versus inhaled, intranasal and sublingual administration. These alternative routes may fail if persons have profuse respiratory secretions. Autoinjector intramuscular injection may continue to be a preferred route of administration for many compounds under most circumstances.

5.1.7 Development of chemical decontamination solutions for use on intact /or injured human skin (improved efficacy compared to soap and water).

5.2 Pulmonary Agents: Development of anti-inflammatory drugs and other medical countermeasures to treat and prevent lung damage from exposure to agents such as chlorine and phosgene.

5.3 Vesicants: Development of medical countermeasures that limit harmful aspects of the inflammatory response following exposure to vesicating agents such as mustards and Lewisite, including topical (skin and eye) and systemic preparations.

5.4 Blood/Metabolic Agents: Development of medical countermeasures to treat poisoning from agents such as cyanides and fluoroacetates under those circumstances where response personnel are immediately present during the limited time between exposure and fatal outcome.

5.5 Toxic Industrial Chemicals and Emerging Threats: Development of medical countermeasures that protect from a wide range of unconventional threats in response to new population threat assessments.

Technical Point of Contact: Dr. Ronald G. Manning; ronald.manning@hhs.gov

Area of Interest #6: Diagnostics:

Design and production of the system in area of interest #6 must be compliant with U.S. Quality Systems Regulations (21 CFR Part 820)

Bio-agent Diagnostics: Submissions for Bio-Agent Diagnostics will not be considered during the open period of this BAA, unless specifically announced through Special Instructions. Please monitor future Special Instructions for specifics on Bio-agent Diagnostics areas of interest.

mailto:ronald.manning@hhs.gov

Biodosimetry Diagnostics:

6.1 Development of a dosimetry self assessment tool for exposures to ionizing radiation at or greater than 2 Gy.

6.2 Development, clinical evaluation, and/or agency clearance of rapid diagnostic systems for determining white blood cell counts from whole blood. These systems should be portable and designed for ease of use by non-expert personnel at point-of-care.

6.3 Biodosimetry Systems -BARDA is interested in white papers based on previously unfunded biodosimetry technologies such as: Metabolomics, Optically Stimulated Luminescence, MicroRNA, Premature Chromosome Condensation, or Fluorescence Activated Cell Sorting. BARDA is not interested at this time in receiving white papers based on currently funded biodosimetry technologies such as: Gene or Protein Expression Changes, Cell micronuclei, Protein Concentration in the Aqueous Humor, Volatile Organic Compounds in Breath, and Electron Paramagnetic Resonance.

In these previously unfunded technologies, BARDA is interested in development of a rapid point-of-care diagnostic or centralized high-throughput assay systems for assessing absorbed doses of ionizing radiation in the range of 0.5 Gy to 10 Gy that have robust detection signal from 24 hours post-exposure and persists at least one (1) week. The assay system should provide the assessment of the absorbed dose for biodosimetry applications with high sensitivity and specificity. It is preferred for high throughput assays to be developed/optimized for use with existing diagnostic instrument platforms which have a large number of US Clinical lab placements and for point-of-care platforms to be CLIA-waived.

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

Chemical Agent Diagnostics:

Submissions for Chemical Agent Diagnostics will not be considered during the open period of this BAA, unless specifically announced through special instructions. Please monitor future special instructions for specifics on Chemical Agent Diagnostics areas of interest.

Technical Point of Contact: Mr. Rodney Wallace; rodney.wallace@hhs.gov mailto:rodney.wallace@hhs.gov

Part II: Research and Technical Objectives The topics listed below exemplify some of the typical developmental activities in the areas of non-clinical research, manufacturing, clinical evaluation, project management, and regulatory strategy contained in a typical drug, biologic or device development effort. This information is provided to assist and guide Offerors in preparing their Statement of Work (SOW). Offerors shall submit a SOW in their full proposal that addresses these topics as appropriate. Provide as much detail as may be necessary to fully explain the proposed technical approach or method. In the event that an offeror’s technical approach provides for performance in excess of one year, the SOW must be presented in a manner so that the base segment and option segments are discrete and non-severable. Each segment must contain specific work elements that must be achieved to support go/no-go milestones that predicate execution of each subsequent option segment of the work.

For drug and biologic medical countermeasure development efforts, Offerors shall propose a Statement Of Work (SOW) preferred to be consistent with activities between Integrated Technology Readiness Levels (TRLs) 6 to 7 (see https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx). For Chemical Radiological and Nuclear (CRN) (Research Areas 4 and 5, Offerors shall propose a SOW that is consistent with activities occurring at TRL 3 or greater (https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx). For diagnostics, Offerors shall propose a SOW that is consistent with activities occurring at TRL 4 or greater (see Attachment 1).

Proposal preparation and submission instructions are contained in Part IV.

For Small Molecules and Biologics, the proposed advanced development program should consist of the following elements when applicable:

Elements of an acceptable SOW might include the following sections for the base and each option:

1.1 Program Management

1.2 Non-Clinical Toxicology

1.3 Non-Clinical PK and Efficacy

1.4 Clinical

1.5 Regulatory

1.6 CMC

Applicable elements may be used to organize the description of effort applied to other areas of interest. The following are detailed examples of the types of activities that may be necessary to implement a program:

A. Development Approach:

1. Program Management Representative Activities include but are not limited to:

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

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

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

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

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

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

2. Non-Clinical Toxicology Research and Development Representative Activities include but are not limited to:

a. Evaluating the safety, toxicology, pharmacokinetics / pharmacodynamics, bioavailability, solubility, formulation, of the medical countermeasure using both in vitro and animal models following Good Laboratory Practice guidelines (GLP:

as defined in the U.S. Code of Federal Regulations -21CFR Part §58), as and when appropriate.

3. Non-Clinical PK and Efficacy Research and Development Representative Activities include but are not limited to:

a. Screening of small molecule libraries for antitoxin/antimicrobial/antiviral activities(for already approved or licensed product).

b. Evaluating the immunogenicity, efficacy, pharmacokinetics/ pharmacodynamics, bioavailability, solubility, formulation, dose, route and schedule of the medical countermeasure using both in vitro and animal models following Good Laboratory Practice guidelines (GLP: as defined in the U.S.

Code of Federal Regulations -21CFR Part §58), as and when appropriate.

4. Clinical Evaluation Representative Activities include but are not limited to:

a. Design and conduct of Phase 1 clinical studies to evaluate the safety and pharmacokinetics of the therapeutic candidate/product in humans in accordance with Good Clinical Practice guidelines (GCP: as defined by 21 CFR §312 and ICH Guidelines document E6.

b. Design and conduct of a Phase 2 and/or Phase 3 clinical studies in accordance with all Federal regulations and GCP guidelines.

5. Chemistry and Manufacturing Controls (CMC) Representative Activities include but are not limited to:

a. Development of master and working cell banks under Good Manufacturing

Practice guidelines (GMP: as defined in the U.S. Code of Federal Regulations –

21 CFR §211).

b. Process development activities to increase efficiency, yield, quality, and reduce the variability and risk factors in the manufacture of the drug substance and drug product.

c. Formulation development to evaluate combinations of excipients and their influence on the target product profile and stability.

d. Manufacture of non-GMP and of GMP pilot lots of candidate product in amounts sufficient to carry out required/proposed non-clinical and Phase 1 and/or Phase 2 clinical trials.

e. Identification of Critical Quality Attributes (CQA) and Critical Process Parameters.

f. Manufacturing scale-up plan to lead to consistency lot manufacturing of the candidate product.

g. Process flow for personnel, material and waste disposal.

h. Proposed packaging design and execution of fill-finish of final drug product.

i. Design of stability testing plan and conduct of stability studies on bulk and final product.

j. Manufacturing/Testing facility plan to support phase I through commercial scale product supply

k. Development of analytical methods and assays appropriate for product characterization and product release, including tests for the identity, purity, potency, and stability of the bulk drug substance and final drug product. Offerors shall identify a stable source and availability of reagents and reference standards for these assays required.

l. Development of Validation Protocol for analytical and assay methods to defining product manufacturing control, performance, potency and product stability indication.

6. Regulatory Activities include but are not limited to:

a. A clear and comprehensive regulatory master plan that focuses on the crucial pathway integrating all products, risk evaluation and mitigation at all development stages, non-clinical and clinical testing, and manufacturing activities using the most current and available information, including documented and time-relevant consultation with FDA. Plan should include a tentative schedule for regulatory milestones.

b. Establishment and filing of regulatory submissions to the relevant FDA center.

b. Maintenance of a plan for additional studies to support future filing for FDA-approval/clearance.

c. Development of a potential Plan for consideration of an Emergency Use

Authorization (EUA) of a medical product (http://www.fda.gov/oc/guidance/emergencyuse.html)

d. Maintaining all required regulatory documentation (investigator brochure, regulatory binder, etc.), providing periodic updates to the FDA as required, and seeking FDA guidance on the conduct of studies that will be used to support approval/licensure/EUA.

http://www.fda.gov/oc/guidance/emergencyuse.html

e. Conducting site initiation, monitoring, and closeout visits to contract research organizations subcontracted to perform studies.

For Diagnostics, the advanced development program should consist of the following elements where applicable:

A. Development Approach:

1. Program Management Representative Activities include but are not limited to:

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

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

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

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

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

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

2. Product Development Representative Activities include but are not limited to:

a. Perform natural/case history studies of threat agent(s).

b. Review the pathology of human disease related to threat agent(s)

c. Identification of biomarkers of disease for threats of interest.

d. Performance of human or non-GLP animal studies to demonstrate the performance / viability of biomarkers.

e. Development of assays, reagents, devices, instruments, and consumables, or components thereof, necessary to perform diagnostic tests, either manually or with automated means. This includes the development of tooling and processes necessary to produce these products.

f. Development of verification and validation protocols and execution of said protocols to prove performance of products developed.

g. Development of reference standard for use in validation and/or verification.

h. Development of requirements and design control documents.

i. Production of non-GMP compliant prototypes and reagent lots at laboratory scale.

3. Manufacturing Development Representative Activities include but are not limited to:

a. Identifying/developing pilot scale manufacturing facilities capable of producing diagnostic systems, assays, reagents, or consumables in compliance with Good Manufacturing Practice guidelines (GMP: as defined in the U.S. Code of Federal Regulations – 21 CFR §211).

b. Process development activities to increase efficiency, yield, quality, and reduce the variability and risk factors in the manufacture of diagnostic devices, assays, reagents, and consumables.

c. Manufacture of non-GMP and of GMP pilot lots of candidate product in amounts sufficient to carry out required/proposed integration, validation, verification, animal studies, or clinical trials.

d. Identification of Critical Quality Attributes (CQA) and Critical Process Parameters.

e. Manufacturing scale-up plan to lead to consistency lot manufacturing of the candidate product.

f. Process flow for personnel, material and waste disposal.

g. Design of stability testing plan and conduct of stability studies assays and reagents.

h. Develop a risk evaluation and mitigation strategy or similar risk mitigation strategy proposal

i. Development of procedures and equipment/components for quality acceptance or quality assurance of manufactured products.

j. Performance of Installation Qualifications (IQ) or Process qualifications (PQ).

k. Development of manufacturing processes and procedures.

l. Development of tooling to manufacture products appropriate for pilot scale manufacturing.

4. Clinical Evaluation Representative Activities include but are not limited to:

a. Design and conduct of clinical trials to evaluate the efficacy, safety, sensitivity and specificity of Diagnostic Systems in humans in accordance with Good Clinical Practice guidelines (GCP: as defined by 21 CFR §312 and ICH Guidelines document E6).

6. Regulatory Activities include but are not limited to:

a. A clear and comprehensive regulatory master plan that includes a strategy for determination of the appropriate regulatory pathway for the developed diagnostic device. Plan should include a tentative schedule for regulatory milestones.

b. Establishment and filing of regulatory submissions to the correct office with the FDA Center for Devices and Radiological Health (CDRH).

b. Maintenance of a plan for additional studies to support future filing for FDA-approval/clearance.

c. Development of a potential Plan for consideration of an Emergency Use Authorization (EUA) of a medical product (http://www.fda.gov/oc/guidance/emergencyuse.html) http://www.fda.gov/oc/guidance/emergencyuse.html

d. Maintaining all required regulatory documentation (investigator brochure, regulatory binder, etc.), providing periodic updates to the FDA as required, and seeking FDA guidance on the conduct of studies that will be used to support approval/licensure/EUA.

e. Conducting site initiation, monitoring, and closeout visits to contract research organizations subcontracted to perform studies.

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 Contracting Officer, and the Contracting Officer’s Representative (COR) shall agree in the 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.

Reports:

1. Technical Progress Reports

On the fifteenth (15) day of each month for the previous calendar month, the contractor shall submit to the Contracting Officer’s Representative and the Contracting Officer a Technical Progress Report covering the previous calendar month. The frequency of Technical Progress Reporting will be determined by the Contracting Officer and Contracting Officer’s Representative during negotiations of the contract. The format and type of Technical Progress Report and Executive Summary will be provided by the Contracting Officer’s Representative. The technical Progress Reports will include project timelines and milestones summaries of 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 attachments to the e-mail report shall be submitted in Microsoft Word, Microsoft Excel, Microsoft Project, and/or Adobe Acrobat PDF files.

2. 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’s Representative and Contracting Officers for review and comments, then the Final Report original, four copies, and an electronic file shall be submitted to the Contracting Officer’s Representative and Contracting Officers for distribution to the Program office.

There may be additional reports and deliverables 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 and Contracting Officer’s Representative. Such meetings may include, but are not limited to, meeting of all Contractors and subcontractors 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 subcontractors and BARDA shall be held to review technical progress.