BAA-13-100-SOL-00013_(BARDA-CBRN).pdf

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

(CBRN) Medical Countermeasures for BARDA

CBRN-BAA-13-100-SOL-00013

Biomedical Advanced Research and Development Authority (BARDA)

330 Independence Avenue, SW, Room G640

Washington, DC, 20201

TABLE OF CONTENTS

TABLE OF CONTENTS

Overview Information…………………………………………………………………..3 Background…………………………………………………………………………….. 7 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 .. .11 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: Application Overview … Section 2: Stage 1 Quad Chart and White Paper Preparation Section 3: Quad Chart and White Paper Submission & Review 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……………………………………………………… .. 48 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…………………………… 68

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 (AMCG), 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, July 31, 2013 as: BAA-13-100-

SOL-00013.

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

Initial Announcement as BARDA CBRN BAA-09-34, issued March 4, 2009 Renewed March 4, 2010 as BARDA CBRN BAA-10-100-SOL-00012 Renewed March 4, 2011 as BARDA CBRN BAA-11-100-SOL-00009 Renewed June 8, 2012 as BARDA CBRN BAA-12-100-SOL-00011

This BAA is available on the following websites:

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

Amendments to this BAA will be posted to the websites listed above when they occur.

Interested parties are encouraged to periodically check these websites for updates and amendments.

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

In accordance with federal statutes, regulations, and HHS policies, no person on grounds of race, color, age, sex, national origin, or disability shall be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any program or activity receiving financial assistance from the HHS.

Research Opportunity Description: The Biomedical Advanced Research and Development Authority solicits the advanced research and development of medical countermeasures for chemical, biological, radiological, and nuclear agents that threaten the U.S. civilian population.

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

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

Research Areas of Interest:

1. Vaccines

2. Antitoxins and Therapeutics

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.

Awards: 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. 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.

The Government 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.

The Government reserves the right to award the instrument best suited to the nature of the research proposed and may award any appropriate contract type under the Federal Acquisition Regulation. If the government contemplates the award of a cost type contract, the offeror must demonstrate prior to award that its accounting system is adequate for administering a cost-reimbursement contract. The Government may also elect to make Other Transactions (OT) agreements.

Cost sharing is not required under this BAA. However, formal or informal cost sharing is encouraged where there is a reasonable probability of a potential commercial application related to the proposed research and development effort.

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

Contact/Submission Information: All submissions and administrative inquires regarding this BAA shall be addressed to CBRN-BAA-13@hhs.gov.

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

When an inquiry is made, please include all pertinent contact information.

Be advised that after a white paper (or full proposal) has been submitted, all communications related to that submission must be through the BARDA Contracting Office (The Office of Acquisitions Management, Contracts & Grants).

Quad Chart and White Papers WILL NOT BE ACCEPTED after 4:30 PM (Eastern Standard Time) on 30 July 2015. Additionally, please note cutoff date submission deadlines under “Application Overview.”

Preliminary Inquiries: BARDA realizes that the preparation of a research proposal often represents a substantial investment of time and effort by the Offeror. In an attempt to minimize this burden, BARDA encourages organizations and individuals interested in submitting research proposals to make preliminary inquiries as to the general need for the type of research effort contemplated before expending extensive effort in preparing a detailed research proposal or submitting proprietary information. Potential Offerors are also encouraged to consult the “BAA Frequently Asked Questions,” available online at http://www.phe.gov/about/amcg/Documents/baa-faq.pdf.

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 mailto:CBRN-BAA-13@hhs.gov.

http://www.phe.gov/about/amcg/Documents/baa-faq.pdf involving expenditure of Government funds.

TechWatch Program: Potential Offerors under this BAA are invited to arrange a meeting at BARDA headquarters through the TechWatch program. Participation in the TechWatch program affords potential Offerors an opportunity to present their capabilities to BARDA scientific subject matter experts and program managers, as well as AMCG contract professionals. These personnel can evaluate products/technologies, suggest techniques and strategies for meeting technical and regulatory challenges, provide insight on how a product or technology may address BARDA's objectives, and provide general information about BARDA's mission and programs. To arrange a TechWatch meeting and for more information about the TechWatch program, potential Offerors should visit the TechWatch website at https://www.medicalcountermeasures.gov/barda/advancing-innovation/techwatch.aspx. Please allow sufficient time for BARDA to schedule a meeting with your organization. Entities with a white paper or proposal currently under review under any ASPR solicitation are not eligible to schedule a TechWatch meeting related to that submission.

Special Instructions: Special instructions will be advertised via the BAA as they become apparent. These additional instructions are tailored to a specific area of interest and may have a unique submittal date. The information requested in these instructions should be used along with Part 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.

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

BACKGROUND

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 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 2012 PHEMCE Strategy and Implementation Plan (https://www.medicalcountermeasures.gov/media/13962/2012-phemce-implementation-plan.pdf.).

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

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.gpo.gov/fdsys/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf)s and The Pandemic and All Hazard Preparedness Reauthorization Act Pub. L. No. 113-5, (PAHPRA:

http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf) authorizes BARDA to https://www.medicalcountermeasures.gov/media/13962/2012-phemce-implementation-plan.pdf http://www.gpo.gov/fdsys/pkg/PLAW-109publ417/pdf/PLAW-109publ417.pdf http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf

(i) conduct ongoing searches for, and support calls for, potential qualified countermeasures and qualified pandemic or epidemic products; (ii) direct and coordinate the countermeasure and product advanced research and development activities of the Department of Health and Human Services; (iii) establish strategic initiatives to accelerate countermeasure and product advanced research and development (which may include advanced research and development for purposes of fulfilling requirements under the Federal Food, Drug, and Cosmetic Act or section 351 of this Act) and innovation in such areas as the Secretary may identify as priority unmet need areas; and

(iv) award contracts, grants, cooperative agreements, and enter into other transactions, for countermeasure and product advanced research and development.

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

• Fewer doses to protection

• Faster protective immune response

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

The proposed vaccine candidate (final formulation) must have 12 months of stability data as measured by acceptable stability indication assay. Preference will be given to candidate products where the final vaccine formulation has demonstrated comparability, non-inferiority preferred, to the current licensed anthrax vaccine under a post exposure prophylaxis (PEP) regimen in a non-clinical study designed to show non-inferiority in a single study. Preference also will be given to vaccine candidate (final formulation) with an active IND and human safety data at time of submission.

1.2 Programs to expand availability of licensed anthrax and smallpox vaccines for at risk populations, e.g. pediatric populations. Interested parties should refer to the Presidential Commission for the Study of Bioethical Issues report on Safeguarding Children: Pediatric Medical Countermeasures report at http://bioethics.gov/cms/sites/default/files/PCSBI_Pediatric-MCM508.pdf

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

2.2 Development of novel formulations of monoclonal anthrax antitoxins already at TRL-7.

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

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

Area of Interest #3: Antimicrobial Drugs mailto:eric.espeland@hhs.gov mailto:stephen.morris@hhs.gov

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).

In accordance with the Pandemic and All-Hazards Preparedness Act of 2006 reauthorized in 2013 (PAHPRA), BARDA has the responsibility to ensure that the United States has a sufficient supply of vaccines and drugs to respond to public health emergencies caused by pandemic influenza, emerging 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 from an equivalent dose and duration of therapy, manufacturing process improvement, etc.) will improve the competitiveness of proposals.

Preferred offerors should have data on in vitro generation of resistance and mechanism(s) of this resistance providing a reasonable expectation that resistance development in the clinic will be slow and rare.

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.

Proposals offering greater developmental maturity and greater therapeutic advantages will be considered more favorably. Substantial improvements over existing antibacterial drugs, novel compounds with unprecedented robust mechanisms of action are urgently needed. If a compound belonging to an existing class (same/similar chemistry and bacterial target) of antibiotic is proposed, there must be significant advantages such as overcoming existing bacterial resistance mechanisms and/or greatly improved drug properties.

Greater technological advancement of the lead compound:

Successive progression through TRL levels and corresponding completion of commercial drug development activities will increase the attractiveness of proposals - Data from IND enabling toxicology studies is a bare essential, improved upon by having filed an IND, and further made attractive with progression into and completion of Phase 1, 2, and 3 clinical studies.

Regulatory feasibility:

Evidence of supportive responses from the FDA concerning the development plan of the drug will reduce risk to a potential investment by BARDA.

Special populations:

Antimicrobials that offer therapeutic benefit to special populations, particularly pediatric subjects, are an important and underserved area. Proposals that have specific plans, likely utility, and proposed activities to advance a product for approved use in special populations will be viewed more favorably.

Cost sharing:

Proposals that demonstrate a commitment of resources from the Offeror in the form of sharing the cost of the proposed development plan are most advantageous. BARDA must operate with a model of public-private partnership in order to broaden and diversify engagements and resources so that likelihood of successes is maximized.

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 Concept-of-Operations (CONOPs) for Radiological and Nuclear Incidents

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

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

24(3):167-78).

• Emphasis is placed on the following MCM qualities:

o Ease of administration o High therapeutic index o Robust storage, easy deployment http://www.medicalcountermeasures.gov/barda/cbrn/broad-spectrum-antimicrobials.aspx mailto:joseph.larsen@hhs.gov http://www.ncbi.nlm.nih.gov/pubmed/19618351

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

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

b. Definitive Care: This treatment phase extends beyond the initial 72 hours of the emergency response. The primary goal is to fully manage a patient’s condition. This includes the full range of preventive, curative, acute, convalescent, restorative, rehabilitative and palliative medical care. Treatment will primarily be administered at medical centers and hospitals operating at surge capacity. Though resources and trained personnel are expected to be strained, their scarcity will not be as severe as that of the Field Care phase.

Radiological and Nuclear Programmatic Priorities

Based on the near-, mid-, and long-term objectives for radiological and nuclear threats prescribed by the Implementation Plan (p. 51-53), BARDA is interested in the following programmatic areas for Area of Interest #4:

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

BARDA will also support the advanced research and development of novel compounds for PEP and treatment of exposure to radiological and nuclear threats.” (p. 53)

4.1 Development of mitigators or treatments for subsyndromes associated with Acute Radiation Syndrome (ARS) and the Delayed Effects of Acute Radiation Exposure (DEARE), arising from exposure to ionizing radiation. The technical readiness level for candidates should be at TRL 5 or higher; Offerors should have submitted pre-IND package to the FDA prior to the submission of a white paper to the BARDA BAA. Treatments that have efficacy when administered after 24 hours post irradiation are of particular interest.

Radiation-induced complications and subsyndromes of interest include:

Neutropenia (definitive care use only)

Thrombocytopenia

Gastrointestinal

Skin (cutaneous)

Lung (pulmonary)

Kidney (renal)

Brain (central nervous system)

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

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

Decorporation Agents

“BARDA will continue to fund projects to support advanced research and development of Prussian blue formulations appropriate for children under the age of two years” (p. 52).

4.2 Development of Decorporation agents (isotopes of interest: Co-60, Sr-90, Cs-137, Po-210, U-235/238, Pu-238/239, Am-241, other transuranics)

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. The technical readiness level for candidates should be at TRL 5 or higher; Offerors should have submitted pre-IND package to the FDA prior to the submission of a white paper to the BARDA BAA. Specific areas of interest within Chemical Threat Medical Countermeasures include:

5.1 Nerve Agents:

5.1.1 Development of a neuroprotectant to prevent and treat hypoxic and/or excitotoxic b rain damage.

5.1.2 Development of an antiseizurogenic that can stop seizures at extended times after seizure onset, when the seizures may have become refractory to current drugs.

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).

5.2 Pulmonary Agents: Development of medical countermeasures, including anti-inflammatory mailto:ronald.manning@hhs.gov drugs, to prevent and treat lung damage from exposure to agents such as chlorine and phosgene.

5.3 Vesicants: Development of medical countermeasures that limit harmful aspects of 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 acute poisoning from agents such as cyanides and fluoroacetates. Antidotes should be easily administered by first responders and safe in all populations.

5.5 Toxic Industrial Chemicals and Emerging Threats: Development of individual MCMs (therapies) that can be used to treat the effects of multiple chemical threat agents and unconventional threats in response to new population threat assessments.

5.6 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.

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

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)

Biodosimetry Diagnostics:

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

6.2 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 mailto:ronald.manning@hhs.gov 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.

Bio-threat agent Diagnostics:

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

6.5.1 Development, clinical evaluation, and/or FDA (“agency”) clearance/approval of rapid, accurate diagnostic systems for determining anthrax infection. These systems should be portable and designed for ease-of-use by non-expert personnel at point-of-care (POC) settings. It is preferred that these POC systems be CLIA-waived; at most they should be CLIA moderately-complex (as opposed to highly complex assay systems).

6.5.2 Development, clinical evaluation, and/or agency clearance of centralized, high-throughput diagnostic assay systems for determining anthrax infection. It is preferred for high throughput assays to be developed and optimized for use with existing diagnostic instrument platforms that have a large number of US clinical laboratory placements, for use with at least one FDA-cleared “routine health-care” assay. BARDA will consider offers if the platform is not cleared to market, but is actively engaged in the clearance/approval process.

For the above, Offerors should provide adequate proof-of-concept data for both proposed assays and platforms—including analytical sensitivity (with limits of detection less than bacteremia levels of 250 CFU/mL), specificity, reproducibility, linearity and dynamic range in relevant clinical matrices, such as whole blood. Mature data packages will receive higher consideration. (Platform performance data may include testing with surrogate agents, e.g. B. cereus, or relevant “routine health-care” assays). BARDA is not interested in white papers or proposals that fail to include convincing proof of concept data.

6.6 Hardware platform development:

6.6.1 In vitro diagnostic (IVD) devices that would provide rapid, accurate point-of-care (POC) / “field-use” testing of the civilian population (including special populations) and results-reporting after a large scale incident resulting in exposure to bio-threat agents of interest. POC platforms should be capable of use at or near the point of need, such as doctors’ offices, hospital emergency room labs, or more austere environments such as in a mobile deployable hospital, school gymnasium, or tent near the site of a bio-threat agent incident. Ideally, these devices would be capable of performing bio-threat and routine healthcare use assays. In addition, these essential elements are sought:

1. Small footprint

2. Ease of use

3. Rapid assay turnaround times, sample to answer results in under

30 minutes (15 minutes preferred)

4. CLIA waive-able or alternatively able to achieve CLIA moderate complexity

5. Ability to be operated in non-temperature/humidity controlled environments.

6. Low cost

7. FDA clearance

6.6.2 New and innovative sample preparation technologies needed for collecting and processing clinical samples potentially containing biothreat agents of interest for use at point of care.

6.7 Fundamental “Bio-threat Agent of Interest” Knowledge Development:

6.7.1 Characterization of pathogen- or disease- specific markers and their relationship to the diagnostic window of opportunity and clinical utility in clinical samples. These studies should be designed to show the clinical relevance of the diagnostic assay, including determination of the most appropriate sample type and matrix.

6.7.2 Assay development of appropriate pathogen- or disease- specific markers including detection methods to provide greatest diagnostic utility.

6.7.3 Studies to inform the clinical effectiveness of the assay in pediatric, geriatric, and other special populations (including immunocompromised, pregnant, and diabetic individuals).

Note 1: “Biothreat Agents of Interest” for sections 6.2 & 6.3 (listed alphabetically):

Bacillus anthracis (Anthrax), Botulinum toxin (Botulism), Burkholderia mallei (Glanders) and Burkholderia pseudomallei (Melioidosis), Filoviruses ( Ebola & Marburg), Francisella tularensis (Tularemia), Rickettsia prowazekii (Typhus), Yersinia pestis (Plague)

Note 2: Animal samples, if required for these studies, will be provided as Government Furnished Material (GFM).

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.

Consequently, contracts awarded under this BAA may contain contract options that may be unilaterally exercised by the government that either follow or run concurrently with a base period of performance. The length of the base period of the contract is subject to negotiation. Offerors are invited to propose certain discrete stages or areas of work as contract options. Contracts awarded under similar BAAs issued in the past by BARDA for the development of innovative platform technologies have had periods of performance ranging from one to five years, inclusive of options.

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:

https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx https://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx http://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx) http://www.medicalcountermeasures.gov/federal-initiatives/guidance/integrated-trls.aspx)

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

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, 21 CFR Part §58), as 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

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.

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

d. 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

e. 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.

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

For Area of Interest #6 (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…