Emergency Medical Countermeasures Development and Acquisition BARDA’s Role and Biodosimetry

1. Emergency Medical Countermeasures Development and Acquisition BARDA’s Role and Biodosimetry Ronald G. Manning, Ph.D. Chief, Chemical, Radiological and Nuclear Medical Countermeasures Project BioShield Biomedical Advanced Research and Development Authority (BARDA)

2. HHS Assistant Secretary forPreparedness and Response (ASPR) Vision: A nation prepared to prevent, respond to and reduce the adverse health effects of public health emergencies and disasters. Mission: Lead the Nation in preventing, preparing for and responding to the adverse health effects of public health emergencies and disasters.

3. BARDA: Roles and Responsibilities • Coordinates an integrated, systematic approach to planning for, and executing research, development and acquisition of medical countermeasures for public health emergencies • Supports the ASPR in leading the Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) • Drives medical countermeasure analysis and prioritization • HHS PHEMCE Strategy for CBRN Threats • HHS PHEMCE Implementation Plan for CBRN Threats • Executes advanced development and acquisition of medical countermeasures for CBRN threats and pandemic influenza • Advanced development under BARDA • Acquisition under Project BioShield (CBRN material threats) • Acquisition with direct appropriations for pandemic influenza CBRN: chemical, biological, radiological, and nuclear

4. HHS Public Health EmergencyMedical Countermeasures Enterprise National Biodefense Science Board BARDA and CDC CDC and DHS CDC and OPEO BARDA NIH CDC FDA Research and Development Biosurveillance/ Detection Advanced Development Storage/Maintenance Deployment Utilization Acquisition PHEMCE COORDINATED PLANNING & EXECUTION

5. HHS Public Health Emergency Medical Countermeasures Enterprise • Purpose: To coordinate across the full spectrum of public health emergency preparedness activities for all intentional and naturally occurring threats  • Established by HHS in July 2006 • Interagency partners include: • Department of Defense • Department of Homeland Security • Veterans Administration

6. Address a diverse set of threats: CBRN and Influenza Consider the needs of a large, diverse population Develop medical countermeasures that are deployable and readily dispensable Prioritize acquisition and advanced development programs with limited funding Face product development challenges: lengthy, risky, and expensive Defining and Prioritizing Medical Countermeasure Development and Acquisition ProgramsScoping the Mission

7. Maximizing Opportunities for Collaboration Building a True Enterprise • Bring together medical and public health assets more effectively • Measurement is vital • Build capacity to perform best practices • Provide coordinated federal assistance to supplement state, tribal, and local resources in response to public health and medical care needs

8. HHS will establish concepts of operations (“conops”), including storage, maintenance, utilization policies and deployment plans for each medical countermeasure in the context of all available consequence mitigation strategies and capabilities. HHS will define specific medical countermeasure requirements, including product specifications consistent with US Government storage plans and operational capabilities for deployment and utilization by federal, state, and local authorities. Establishment of Medical Countermeasure Requirements

9. Medical Countermeasure Preparedness for CBRN Threats • CHEMICAL THREATS BIOLOGICAL THREATS • Anthrax • AVA Vaccine • Oral ciprofloxacin • Doxycycline • Amoxicillin • Other IV antibiotics • Human polyclonal antibody • Botulism • Antitoxins from legacy DOD program and legacy CDC/Cangene program • Other monovalent and bivalent antitoxins • Plague • Antibiotics • Smallpox • Smallpox vaccines (MVA and ACAM2000) • Vaccinia Immune Globulin (VIG) • Tularemia • Antibiotics • CHEMPACKs • RADIOLOGICAL / • NUCLEAR THREATS • KI tablets and Pediatric KI • Prussian Blue • Cytokines • Antibiotics • Anti-emetics • Blast and burn supplies • Ca & Zn DTPA

10. Radiological/Nuclear Threats • Nuclear Detonation • Radiologic dispersive devices (“dirty bombs”) • Industrial and shipping accidents • Power plant releases • Food and medical irradiators • Sealed sources

11. Radiation Exposure Events • IND Models for a 10 KT event estimate 1.8 million affected • 1 million may seek information on their personal risk (dosimetry), • Hundreds of thousands estimated to receive > 2 Gy if event occurs in a large metropolitan area adapted from: Blood, 15 June 2008, Vol. 111, No. 12, pp. 5440-5445.

12. Triage and Patient Monitoring after an IND Event NO mass casualty biodosimetry capabilities at this time • TRIAGE • People requiring immediate medical intervention (burns, fractures, blood loss) • People receiving radiation doses > 2 Gy (risk of hematological ARS) • Concerned citizens • Expectant (likely to die) • Complications: Many inhomogeneous irradiations (partial body exposures) • Correct triage and treatment depends on rapid and accurate radiation dose estimates • Currently a multi-parametric approach is used to estimate radiation dose: • Location relative to event • Time from event to first emesis • Peripheral blood lymphocyte counts & depletion kinetics (hours to days) • The utility of these measures in response to an IND event is not clear. 11

13. Current Biodosimetry Capacity Biodosimetry capability will be integral to triage, treatment, and medical management of radiation-exposed individuals. Dose evaluation based on clinical signs and symptoms can lead to a high level of false positives and lead to unneeded treatment. The "gold standard" for biodosimetry is chromosomal aberrations (i.e. dicentrics). Dicentric quantification requires several days to perform; is labor intense; is only available in specialized centers (a Laboratory Response Network is in development). Immediate need: Rapid dose assessment tools or bioassays.

14. CBRN Dosimetry Objectives • Pursue diagnostic capabilities for dose determination • Physical dosimetry tools for exposure • Rapid biodosimetry assays to estimate doses >2 Gy • Rapid biodosimetry assays to determine dose 1 – 20 Gy • Gold standard assays using novel biomarkers – i.e. organ-specific radiation injury/susceptibilities • Rapid determination of radionuclide exposure and body burden

15. ANY QUESTIONS????? Contact Information: BARDA@hhs.gov www.hhs.gov/aspr/barda www.medicalcountermeasures.gov