united states department of health & human services

ASPR: Resilient People. Healthy Communities. A Nation Prepared.

United States Department of

Health & Human ServicesOffice of the Assistant Secretary for Preparedness and Response

Building the Plane…While Flying

Debra A. Yeskey, Pharm. D.Director, Regulatory & Quality Affairs

BARDA/ASPR/HHS

November 19, 2013

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 2

Boeing 747SP


• Building and Flying: ─ The infrastructure─ A decade of MCM product development

• Looking into the Future

Objectives


Man-Made & Mother Nature’s Threats Have Become Reality Since 9/11


Medical Countermeasures

Antimicrobials Diagnostics VaccinesMedical Devices Therapeutics


MCMs are Needed for Public Health and National Security

• The tools to manipulate biological agents are increasing exponentially in power and becoming more widespread and affordable, increasing the risk they will be misused.

• Mother Nature is relentless with SARS, H5N1, H1N1, H7N9, and MERS-CoV in the past ten years.

• Medical countermeasures, and hence BARDA and the Special Reserve Fund, remain central to our national security and public health well being now and for the foreseeable future.

• MCM development is lengthy, expensive, and risky requiring sustained commitment; failure to maintain USG investment at current levels will dramatically erode private sector confidence and partnerships.


• Threat Assessment/Determination (DHS)• Medical Consequence Modeling (HHS/BARDA)• Medical Countermeasure Requirements (HHS/ASPR with

PHEMCE)• Medical Countermeasure Discovery & Early Development

(NIH & DoD)• Medical Countermeasure Advanced Development

(HHS/BARDA)• Unlicensed Medical Countermeasure Acquisition

(HHS/BARDA)• Licensed Medical Countermeasure Acquisition

(CDC/SNS)

PHEMCE Process: Threat Assessments to Medical Countermeasures


Public Health Emergency Medical Countermeasures Enterprise

PHEMCE COORDINATED PLANNING& EXECUTION

ASPR/BARDA

NIH CDC and ASPR/OPEO

R & D Advanced Development

Acquisition & Stockpiling

Storage/Maintenance

Deployment & Recovery

FDA

CDC/SNS BARDA

ASPR/OPP

Requirements Evaluation

CDCASPR

FDA

BARDACDC/SNS

National Biodefense Science Board


BARDA Organization

DirectorDr. Robin Robinson

Principal Deputy DirectorDr. Carol Linden

Chief Medical Officer& Deputy DirectorDr. Richard Hatchett

CBRNDirector

Dr. Gerald KovacsDeputy Director

Dr. Gary Disbrow

Pandemic InfluenzaDirector

Dr. Robert HuebnerDeputy DirectorDr. Rick Bright

Regulatory andQuality Affairs

DirectorDr. Debra Yeskey

Clinical StudiesDr. Jo Schweinle, Director

Strategic Science& TechnologyDr. Jonathan Seals, Director

Analytical Decision SupportDr. Tim Lant, Director

Manufacturing,Facilities

and EngineeringTom Warf. Director


10

10

BARDA’s Commitment to Medical Countermeasures

Develop and provide countermeasures for CBRN threats, pandemic influenza, and emerging infectious diseases by

product development, stockpile acquisition, building manufacturing infrastructure building, & product innovation.


Regulatory and Quality Affairs is a BARDA Core Service.

11

Centers for Innovation in

Advanced Development & Manufacturing

Fill Finish Mfg. Network

Nonclinical Network

Clinical Studies

Network Strategic

Innovations Portfolio

ADS Modeling

Hub

Regulatory & Quality Affairs

2009

2012

2013

2010

2013TBD

2006


RQA Support

12

Regulatory Support

Regulatory Ops

Quality Support

We provide BARDA and our Sponsors comprehensive capabilities in regulatory affairs and quality monitoring.


Building and Flying: a decade of MCM product development


Discovery Phase I Phase II LicensurePhase IIIPreclinicalDevelopment

Production & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PRO

DU

CT

PIPE

LIN

EPR

OD

UC

T PI

PELI

NE

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND NDA/BLA

PHASESPHASES

NIH ($11.8B)BARDA ($540M)

Project BioShield ($5.6B)

Discovery Phase I Phase II LicensurePhase IIIPreclinicalDevelopment

Production & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PRO

DU

CT

PIPE

LIN

EPR

OD

UC

T PI

PELI

NE

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND NDA/BLA

PHASESPHASES

NIH ($11.8B)BARDA ($540M)

Project BioShield ($5.6B)BARDA ($2.0 B)

NIH ($15.6 B)

3-7 yr 0.5-2 yr 1-2 yr 2-3.5 yr 2.5 -4 yr 1-2 yrs TIME

$100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20MPIPELINEPHASE COST

Valley of

Death

BARDA Bridges the MCM “Valley of Death” to Reduce Cost, Time, && Risk


• Preparedness─ Long-term storage…”Trust us we’re the government”─ IND then EUA

• Regulatory Issues─ CBER and CDER─ Aggressive timelines─ Labeling: IND to Approved/Licensed─ Animal Rule/Phase 4 Commitments─ Qualification of animal models─ Advisory Committee Meetings─ Normal stuff…

Fitting Regulatory into a Preparedness Paradigm…


BARDA Created a Robust & Productive MCM Development Pipeline

• More than 150 MCM product candidates in development since 2004

PAHPAPBSMCM

Review

2004 2005 2006 2007 2008 2009 2010 2011 2012 20130

20

40

60

80

100

120

140

160

180

FLUCBRN

PAHPRAH7N9

H1N1H5N1


BARDA Has Established Robust CBRN MCM Development Pipeline

• BARDA CBRN MCM development pipeline has supported 80+ candidates since 2004 ($2.2 B)

• Biothreats • Anthrax vaccines (7) and antitoxins (7)• Smallpox vaccine (3) and antiviral drugs (2)• Botulinum antitoxin (1)• Other biothreat antimicrobial drugs (7)

• Rad/Nuc threats• Acute Radiation Syndrome drugs (36)• Decorporation agents (6)• Thermal burn therapies (4) • Biodosimetry devices (11)

• Chem threats – antidotes & decon (4)


BARDA Delivered New MCMs under Project BioShield

Botulism

Anthrax

Smallpox

Radiation


BARDA Nurtured Influenza Vaccine Development to Achieve National Pan Flu Vaccine Goals

Cell-based Vaccines

Egg-based Vaccines

Recombinant-based Vaccines

Universal Vaccines

Antigen-Sparing Vaccine Technology

“More and better vaccines sooner”

FluBlOk Licensed 01/16/13

FlucelvaxLicensed 11/20/12

H5N1 vaccine Licensed 2007

Q-PAN H5N1 Vax

BLA submitted 2012


BARDA Built and Expanded National Pan Flu MCM Readiness Infrastructure

• Established a pre-pandemic vaccine stockpile of H5N1 vaccine antigens & adjuvants ($1.5 B) & a H7N9 vaccine stockpile this Fall ($110 M).

• Procured initial federal antiviral drug stockpile & managed State antiviral drug stockpile procurement ($1 B)

• Rebuilt domestic flu vaccine manufacturing infrastructure ($1 B)• will address domestically nearly 90% of U.S. pan flu vaccine need• secured the egg supply, • build and retrofitting facilities• established Centers for Innovation in Advanced Development & Manufacturing

• Led product development towards FDA approval of vaccines (9) and diagnostics (3), EUA-issuance for antiviral drug during 2009 H1N1 pandemic, and anticipated approval of more vaccine (1) and diagnostics (3) in FY2013

• Leads vaccine development & stockpiling for current H7N9 outbreaks


Recently FDA Approved BARDA-supported MCMs

Novartis Protein Sciences

Recombinant-based Influenza Vaccine

Anthrax Antitoxin

HGS/GSKBotulinum Antitoxin

Cangene

Covidien

Next-Gen Portable Ventilators

Cell-based Influenza Vaccine

Flu/RSV POC Diagnostic

3M/Focus

http://media.wkrg.com/images/sized/media/news3/10-13-2008_peyton-300x200.jpg


Looking into the Future


BARDA’s Core Services

23

Centers for Innovation in

Advanced Development & Manufacturing

Fill Finish Mfg. Network

Nonclinical Network

Clinical Studies

Network Strategic

Innovations Portfolio

ADS Modeling

Hub

Regulatory & Quality Affairs

2009

2012

2013

2010

2013TBD

2006


BARDA Uses Public-Private Partnerships to Build Domestic MCM Manufacturing Capacity

• Retrofitting Vaccine Manufacturing Infrastructure

sanofi pasteur – Swiftwater, PA

• Changing Flu Vaccine Industry

Novartis – Holly Springs, NC


BARDA Assists MCM Developers Directly with Product Development & Manufacturing


BARDA Assists MCM Developers thru our Animal Models Network

Battelle Memorial Institute

BioQUAL, Inc.

University of Illinois, Chicago

IIT Research Institute

Lovelace Respiratory Research Institute MRIGlobal

University of Texas Medical Branch

SRI International

Southern Research

Health Protection Agency, Porton Down

Defence Science and Technology Laboratory, Porton Down

Battelle Pacific Northwest Division


MULTIFUNCTIONALGlaxo-Smith Kline:Broad spectrum antibioticsUsing Other Transaction Authority Agreement

BARDA Prioritizes Repurposed and Multipurpose MCM Candidates

REPURPOSEDRomark: NitazoxanideFDA-Approved for parasitic infectionsUnder development for influenza, & MERS-Cov


• Universal influenza vaccine• Volatile nerve agent countermeasures• Novel broad-spectrum antimicrobial drugs• Viral hemorrhagic fever MCMs• Radiation countermeasures

─ Acute radiation countermeasures─ Oral decorporation agents─ Biodosimetry/bioassays─ Skin/lung countermeasures

• Thermal burn therapies• Blood products• Diagnostics

MCM Gaps for BARDA to Fill


• Implementing new strategies to repurpose & multipurpose MCMs

• Developing sound utilization strategies and ConOps• Transfer of technologies to CIADM facilities• Qualifying new animal models

Current BARDA MCM Challenges


In the End…

FDA expects Industry executives and their teams to take a holistic, cross-functional, risk-based, proactive approach to regulatory product development to ensure patient safety and product efficacy …and so do we.

Invest in compliance, build quality into your product, beginning, middle and end.

united states department of health & human services

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resilient people

healthy communities

medical countermeasuresdevelop

mcm development

boeing 747sp1 aspr

stockpile acquisition

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