Presentation Slides - March 23 2011.pdf

CBRN MCM Development

“Rolling” BAA BARDA CBRN11-100-SOL- 00009

Pre-Proposal Conference

23 MAR 2011

BARDA / AMCG Staff

2:00 pm Welcome and Q&A

2:30 pm Introductions

2:35 pm Overview of BAA Process/Changes

2:50 pm Break

3:00 pm Overview of Areas of Interest

3:40 pm Open Discussion/Questions

4:00 pm Adjourn

Agenda

CBRN BAA Team

• Dr. Eric Espeland – Project Officer

• Dr. Mary Homer – Project Officer

• Glynis Fisher – Contracting Officer

• Ethan Mueller – Contracting Officer

• Carl Newman – Contracting Officer

• Carolyn Keeseman – Contracting Officer

• Matt McCord – Contracting Specialist

Technical Points of Contact

• Dr. Eric Espeland – Vaccines

• Dr. Stephen Morris – Antitoxins and Therapeutics

• Dr. Joe Larsen – Antimicrobial drugs

• Dr. Ron Manning – Rad/Nuc/Chem MCM

• Mr. Rodney Wallace – Diagnostics

CBRN Broad Agency Announcement

Process Overview

Purpose of the BAA

• Identify innovative and promising technologies for advanced development across CBRN Research Areas of Interest

─ Vaccines

─ Antitoxins and Therapeutics

─ Antimicrobial Drugs

─ Radiological/Nuclear Threat Countermeasures

─ Chemical Threat Countermeasures Diagnostic

• Accelerate contract awards with a flexible solicitation

• Build a sustainable advanced development program to meet

PHEMCE implementation plan goals and mature MCMs for eventual FDA approval and possible inclusion in the

Strategic National Stockpile.

Cat II Scientifically & technically sound proposals with potential to advance program goals and objectives, provided substantial, further development. Need for changes and additional data/explanation is significant enough to require revised proposal. If invited for new proposal, a new technical review may be required to determine reassigning to Cat I.

Cat II proposals are handled at lower priority than Cat I and are not guaranteed to be invited for resubmission.

Cat III Proposals not technically sound or do not meet program goals and objectives. Cat III have lowest priority and will be rejected.

Cat I Well conceived scientifically & technically sound proposals important to program objectives. Recommended for negotiation and possible acceptance, subject to funds availability.

Within 90 days

Within 180 days

Publish BAA Receive

Incoming White Papers

Evaluate White

Papers

Peer Review

Panel

Regrets Notification

Not Acceptable

Acceptable

Full Proposal Invitation

Source Selection

Evaluation Board

Evaluate Proposal

Cat I Cat II Cat III

Contract

Award

Resubmission

Negotiations

CBRN Broad Agency Announcement

Changes to 2010 BAA 100-SOL-00012

• 2011 BAA will be open for 12 months (4 March 2011 – 3 March 2012).

• Full Proposal Length will return to 50 pages for technical proposals and 50 pages for cost proposals with 70 pages for appended material unless otherwise specified in the full proposal invitation letter

• Updates have been made under each Area of Interest #1, 3, 4, and 6

• TRL guidance for Chem/Rad/Nuc MCM (Area of Interest #4) has moved from TRL

6-7 to TRL 3 or greater (see attachment 1)

• New language has been incorporated regarding subcontracts under Basic

Cost/Price Information (see Part IV, Sec 4C, item iv)

• Definitions for Cat I and Cat II proposal classifications have been refined

• For Chem/Rad/Nuc, new language has been added under the technical proposal for proof-of-concept studies (see Part IV, Sec 4, A.9)

• Requirements language has been revised in Part VII, Attachment 8

• Submission Deadlines

USG Response

Receipt confirmation within 1 week; Decision within 90 days

Receipt confirmation within 1 week

Within 180 days of Full Proposal

Receipt

Deadline for Submission

Dec 1, March 1, June 1 and

September 1 for Areas 1, 2, 3, 6;

Anytime for Areas 4 and 5

Within 75 days of Invitation

(pending availability of funds)

Proposal Stage

Stage 1: Quad Chart and White Paper

Stage 2: Full Proposal

Source Selection Notification (pending availability of funds)

Key Items to Remember…

• Security waiver

• Communications

─ All pre-award communications must flow through Contracting

Officer

─ Period following white paper submission consists of no communication until decision letter is received

• All White Paper proposals should be sent to:

CBRN-BAA-11@hhs.gov

• Notification of White Paper decisions

Rating your Technology Readiness Level

• Detailed TRL criteria are located in Attachment 1 (Diagnostic

Devices) & www.medicalcountermeasures.gov (biologics and drugs)

Key to rating your TRL:

When using these criteria, a medical countermeasure product should be rated at a particular level only after the sponsor has completed all activities listed in that level (e.g., a product is rated at TRL 4 once it completes all of the activities listed in TRL 4).

http://www.medicalcountermeasures.gov/

Example for Biologics and Drugs per www.medicalcountermeasures.gov

(go to Federal Initiatives tab, select guidance) http://www.medicalcountermeasures.gov/

Questions?

Technical Areas of Interest

Mike Merchlinsky, Ph.D.

Subject Matter Expert, Smallpox Vaccines Branch

HHS/ASPR/BARDA

BAA - Research Area #1

Vaccines

Biomedical Advanced Research and Development Authority (BARDA)

Research and Development Focus (AOI1)

• 1.1 Development of new vaccine/adjuvant formulations; use of approved or novel adjuvants in conjunction with a specific vaccine to achieve desired improvements like enhanced efficacy, antigen-sparing or lower adverse effects.

• 1.2 Development of desired capability improvements for vaccine attributes such as enhancements in formulation and delivery methods, time to protection, duration of protection, product stability and shelf-life.

• 1.3 Product development of a vaccine/adjuvant candidate formulated for a specific application including non-clinical, clinical development, manufacture at pilot scale under GMP;

process development and scale up including fill-finish; assay methods for drug substance and product release, stability, and characterization.

Additional Comments:

• Use space efficiently in white papers; supporting data is important to evaluate proposal development program, use tables and figures.

─ Stay on message! More is not always better…

• Full proposals should convey a clear development plan that can be followed logically.

• Propose realistic schedules and costs.

Technical Program of Contact:

Dr. Eric M. Espeland

202-205-7057 eric.espeland@hhs.gov

All administrative inquires regarding this BAA shall be addressed to: CBRN-BAA-11@hhs.gov

This BAA is available on the following websites:

• https://www.fbo.gov

• https://www.medicalcountermeasures.gov/

• http://www.hhs.gov/aspr/barda/ mailto:eric.espeland@hhs.gov

Terri Richards

Project Officer, Antitoxins and Therapeutics

HHS/ASPR/BARDA

BAA - Research Area #2

Antitoxins and Therapeutics

Technical Goals (AOI2)

• Provide medical countermeasures for PHEMCE priorities based on toxins and infectious diseases

• Support advanced development of antitoxins and therapeutic proteins

• Consider near-, intermediate-, and long-term solutions based on a variety of technologies

Technical Objectives (AOI2)

• 2.1 Development of a multivalent botulinum toxoid for hyper-immune plasma production

─ Human and equine plasma focus

─ Near- and intermediate-term solutions for USG

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

─ Anthrax and botulism priorities

─ Intermediate- and long-term solutions for USG

─ Formulated for oral, im, or iv delivery

• 2.3 Development of monoclonal anthrax antitoxins including non-clinical studies, completion of Phase 1 trial, initiation of a Phase 2 clinical trial, manufacturing at pilot scale under GMP, process development and scale-up including fill-finish.

─ Near-term solutions for USG

─ Includes studies and manufacturing needed to support BLA

─ Includes studies and manufacturing needed to support preparation of pre-EUA and IND packages by CDC

• 2.4 Development of novel formulations of monoclonal anthrax antitoxins

─ Near-term solution for USG

─ Includes lyophilization process development

• 2.5 Development of monoclonal antibody treatments and other therapeutics for viral hemorrhagic fever agents

─ Intermediate- and long-term solutions for USG

─ Includes Ebola, Marburg, Junin viruses

Closing Comments

• Be clear and concise, use charts and tables for data

• Do not repeat text or data in several places

• Use the allowed pages wisely

• Don’t feel obliged to use all the allowed pages

• Tell the best story possible, sell the strong points

• Know your limitations, don’t conceal the weak points

• Have a management plan for your work and for subcontractors’

• Include document review in timelines

• Include risk plan

• Schedule a Tech Watch meeting before submitting the white paper

Dr. Stephen Morris

202-260-0441 stephen.morris@hhs.gov

• Ms. Terri Richards

─ terri.richards@hhs.gov

• Dr. Chia-Wei Tsai (anthrax antitoxin ARD leader)

• Dr. Melissa Willis (botulinum antitoxin ARD leader) mailto:stephen.morris@hhs.gov mailto:terri.richards@hhs.gov

Joseph C. Larsen, Ph.D.

Chief, Broad Spectrum Antimicrobials Branch

HHS/ASPR/BARDA

BAA - Research Area #3

Antimicrobial Drugs

BAA-Area of Interest #3 (AOI3)

• Broad Spectrum Antimicrobial (BSA) program is establishing partnerships with Offerors that advance drug candidates for both biodefense and commercial indications

• AOI3 supports research and development activities for clinically relevant infectious disease indications concurrently with biodefense development activities

• Preliminary biodefense data is viewed as a strength

• Proposal timelines should be structured to obtain biodefense data upfront (Years 1 & 2)

• Gram-negatives are of primary interest, but anthrax may be included in proposed testing scheme if broad spectrum activity is demonstrated in vitro

Research and Development Focus (AOI3)

• 3.1 Development of novel small molecule antiviral candidates with activity against one or more biodefense threat agents

(Ebola, Marburg, Junin, 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) applying relevant aerosol challenge models

Research and Development Focus (AOI3)

• 3.3 Repurposing or combining currently approved antivirals or antibiotics for prophylactic, PEP or therapeutic use against multiple biodefense threat agents (a single agent is permitted in the case of antivirals only). Repurposing currently approved pharmaceuticals originally developed for other indications, provided that the proposal can document the necessary sponsorship to obtain a label change. Testing parameters employed should be similar to those described in section 3.2.

• 3.4 Determination of antibiotic regimens or combinations which are capable of treating Burkholderia mallei and Burkholderia pseudomallei infections in relevant animal models

Research and Development Focus (AOI3) cont.

• 3.5 Provision of a task order-driven, in-vitro, and murine model testing service to evaluate early stage antimicrobial drug candidates directed against infection with Gram (-) bacterial threat agents. This would include the development and testing of intravenous or intramuscular formulations for Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei

QUESTIONS?

Dr. Joseph C. Larsen

202-260-0050 joseph.larsen@hhs.gov

All administrative inquires regarding this BAA shall be addressed to: CBRN-BAA-11@hhs.gov

This BAA is available on the following websites:

• https://www.fbo.gov

• https://www.medicalcountermeasures.gov/ mailto:joseph.larsen@hhs.gov

Ron Manning, Ph.D.

Chief, CRN Branch

HHS/ASPR/BARDA

BAA - Research Areas #4 and #5

Radiological/Nuclear Threat Countermeasures

Chemical Threat Countermeasures

BAA-Area of Interest #4 (AOI4)

• 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 no earlier than 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)

• 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)

BAA-Area of Interest #5 (AOI5)

• Nerve Agents

• Pulmonary Agents

• Vesicants

• Blood/Metabolic Agents

• Toxic Industrial Chemicals and Emerging

Threats

CRN Considerations

• 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

• Target/Candidate Identification and Characterization of Preliminary

Candidate(s)

─ Begin research, data collection, and analysis in order to test hypothesis.

Explore alternative concepts, identify and evaluate critical technologies and components, and begin characterization of candidate(s). Preliminary efficacy demonstrated in vivo.

─ 3A Identify target and/or candidate.

─ 3B Demonstrate in vitro activity of candidate(s) to counteract the effects of the threat agent.

─ 3C Generate preliminary in vivo proof-of-concept efficacy data (non-GLP

(Good Laboratory Practice)).

• Deadline for Submission is anytime for CRN

Acute Radiation Syndrome Scenario-based

Requirements

• The civilian requirement for medical countermeasures is a suite of countermeasures to increase survival

• Details of the medical countermeasures would greatly impact how the agent(s) would be procured, stockpiled, resource-shared, vendor-managed, or otherwise made available

Dr. Ronald Manning

202-260-0400 ronald.manning@hhs.gov

All administrative inquires regarding this BAA shall be addressed to: CBRN-BAA-11@hhs.gov

This BAA is available on the following websites:

• https://www.fbo.gov

• https://www.medicalcountermeasures.gov/ mailto:ronald.manning@hhs.gov

Rodney Wallace

Chief, CBRN Diagnostics

HHS/ASPR/BARDA

BAA - Research Areas #6

Diagnostics

Products of Interest

• Countermeasure - a therapeutic drug, vaccine or medical device to counteract or prevent the effects of a biowarfare threat; or a Diagnostic System to inform use of the therapeutic drug or vaccine.

• Diagnostic System – all the components required to yield a diagnostic result capable of informing patient treatment, from a clinical sample.

Advanced Research And Development Funds

• Funding may be used to further the development and maturity of

Diagnostic Systems toward FDA clearance/approval

• These funds should not be used beyond the FDA clearance/approval milestone.

• Equipment

─ This BAA should not fund acquisition of equipment except under very specialized circumstances, such as:

• Equipment is essential to complete the proposed research and the contractor would not have other commercial justification for acquiring the equipment.

• Equipment is essential to manufacture clinical materials for a pilot manufacturing capability and the contractor would not have commercial justification for acquiring the equipment.

─ Lease Equipment where possible.

Regulatory Requirements

• Diagnostics funded under this BAA are for medical countermeasures and must inform patient care.

─ Center for Devices and Radiological Health (CDRH) @FDA

─ All product development funded by this BAA shall be working to attain FDA clearance/approval, or other US regulatory approval such as EUA for the proposed product. Appropriate actions along the path to approval shall be included in white papers & proposals.

Diagnostics Technology Readiness Level (TRL) Attachment 1

• TRL 1 Basic Research

• TRL 2 Basic Invention

• TRL 3 Initial Validation of Analytical Components

TRL 4 Transition from Research to Development

Non-GLP research

Initial specifications for device, systems, and subsystems determined.

Procedures for Use Drafted

In-house testing

Potential safety problems identified through risk analysis.

Ad hoc hardware in a laboratory. Basic software as applicable.

• TRL 5 Product Development/ Begin Design Controls

• TRL 6 Pre-Clinical / In-House Testing

• TRL 7 Investigational Phase

• TRL 8 Use in Actual Setting with Clinical Samples

• TRL 9 Used in Clinical Settings with Clinical Samples, Post-Market Studies or Data Collection as applicable

Bio-agent Diagnostics – Threats of Interest

Threat Agent PHEMCE CDC

Bacillus anthracis (Anthrax) A

Botulinum Toxin (Botulism) A

Burkholderia mallei & pseudomallei (Glanders & Meloidosis) B

Filoviruses (Ebola & Marburg) A

Francisella tularensis (Tularemia) A

Junin Virus (Argentine Hemorrhagic Fever) A

Rickettsia prowazekii (Typhus) B

Variola Virus (Smallpox) A

Yersinia pestis (Plague) A

Areas Of Interest 6.1-6.4

Bio-agent Diagnostics – Areas of Interest

AOI Topic

6.1 Point of Care Diagnostics

6.2 New Methods to Detect Circulating

Toxins

6.3 High Throughput Diagnostics on

Existing, Fielded Automation

6.4 Simple Reliable Sample collection and

Preparation Methods

Bio-agent Diagnostics – Areas of Interest

AOI Topic

6.5 Physical Dosimetry Self Assessment

Tool

6.6 Portable White Blood Cell Counts

6.7 POC or HT Biodosimetry Systems

6.8 Improvements on Dicentric

Chromosomal Assay

Biodosimetry Preferred Attributes

AOI 6.7 (Attachment 8)

Point of Care Device (POC) High Throughput Device (HT)

Type of result: Qualitative Quantitative (accuracy 0.5Gy)

CONOPs: Initial Triage / Sorting Injury Assessment / Treatment

Exposure level: 2 Gy (200 rad) (threshold) Range: 0.5 – 10 Gy

Ease of operation:

Easy to operate, minimal complexity (requires minimal training ;CLIA waived)

Laboratory instrument—more labor intensive, requires training

Device characteristics:

Integrated components—no separate sample preparation

May include separate components as needed. High automation desired.

Intended use: Tents, shelters, open settings Labs, hospitals, fixed facilities

# Patients / Event Up to 1,000,000 in 6 days Up to 400,000 (may need multiple assessments)

Time to result: Rapid but individual sample result

(< 30 minutes)

Up to 24 hours

Chemical Agent Diagnostics - Areas of Interest

AOI Topic

6.9 Diagnostics for: Chemical nerve agents, pulmonary agents, vesicants (mustard agents), blood/metabolic agents, TICs, and emerging threats.

Rodney Wallace

202-205-3983 rodney.wallace@hhs.gov

All administrative inquires regarding this BAA shall be addressed to: CBRN-BAA-11@hhs.gov

This BAA is available on the following websites:

• https://www.fbo.gov

• https://www.medicalcountermeasures.gov/