Emergency Medical Countermeasures Emergency Medical Countermeasures Development and AcquisitionDevelopment and Acquisition

BARDA’s Role and Biodosimetry BARDA’s Role and Biodosimetry

Ronald G. Manning, Ph.D.Chief, Chemical, Radiological and Nuclear

Medical CountermeasuresProject BioShield

Biomedical Advanced Research and Development Authority (BARDA)

ASPR HHS Assistant Secretary forPreparedness and Response (ASPR)

ASPR

Office of Medicine,Science,

& Public Health

Office of Policy & Strategic

Planning

Immediate Office of the ASPR

Biomedical Advanced Research

& Development Authority

Office of Preparedness &

Emergency Operations

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.

ASPR

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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

ASPR HHS Public Health EmergencyMedical Countermeasures Enterprise

BARDANIH CDC CDC and OPEO

UtilizationResearch and Development

Advanced Development Acquisition Storage/

MaintenanceBiosurveillance/

Detection

PHEMCE COORDINATED PLANNING& EXECUTION

BARDA and CDC

National Biodefense Science Board

Deployment

CDCand DHS

FDA

ASPR

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

HHS Public Health Emergency Medical Countermeasures Enterprise

Interagency partners include:Department of DefenseDepartment of Homeland SecurityVeterans Administration

ASPR Defining and Prioritizing Medical Countermeasure Development and Acquisition Programs

Scoping the Mission

Develop medical countermeasures that

are deployable and readily dispensable

Address a diverse set of threats:

CBRN and Influenza

Consider the needs of a large, diverse population

Prioritize acquisition and advanced

development programs with limited funding

Face product development challenges:

lengthy, risky, and expensive

ASPR 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

ASPR Establishment of Medical Countermeasure Requirements

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.

ASPR

Plague Antibiotics

Smallpox Smallpox

vaccines (MVA and ACAM2000)

Vaccinia Immune Globulin (VIG)

Tularemia Antibiotics

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

Medical Countermeasure Preparedness for CBRN Threats

BIOLOGICAL THREATS

KI tablets and Pediatric KIPrussian BlueCytokinesAntibioticsAnti-emeticsBlast and burn suppliesCa & Zn DTPA

RADIOLOGICAL / NUCLEAR THREATS

CHEMICAL THREATS CHEMPACKs

ASPR

Radiological/Nuclear Threats

Nuclear Detonation Radiologic dispersive

devices (“dirty bombs”)

Industrial and shipping accidents Power plant releases Food and medical

irradiators Sealed sources

ASPR

11adapted from: Blood, 15 June 2008, Vol. 111, No. 12, pp. 5440-5445.

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

Radiation Exposure Events

Event Description Potential Numbers Affected

Radioactive Source Accident

Hospital irradiation source (Co-60)Industrial x-ray source (Ir-192)

Example: Goiania (Cs-137 source)individuals to many

Nuclear Reactor Accident

Release of radioactive materialExample: Chernobyl

individuals to hundreds(can cover large

geographical area)RDD –

Radiological Dispersal Device, “Dirty Bomb,” or Exposure Device

Improvised explosive device containing radioactive material May include food chain contamination Cs-137 or Ir-192 sources on a subway

individuals to thousands

Improvised Nuclear Device

(IND)

A true, or assembled, nuclear device capable of a nuclear detonation thousands to > 1 million

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NO mass casualty biodosimetry capabilities at this time

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Triage and Patient Monitoringafter an IND Event

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.

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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 quantificationo requires several days to perform;o is labor intense;o is only available in specialized centers (a Laboratory Response

Network is in development).

Immediate need: Rapid dose assessment tools or bioassays.

ASPRCBRN 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

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ASPR

Contact Information:

BARDA@hhs.gov

www.hhs.gov/aspr/barda

www.medicalcountermeasures.gov

ANY QUESTIONS?????