ASPR: Resilient People. Healthy Communities. A Nation Prepared. United States Department of Health & Human Services Office 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. Boeing 747SP 1

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 2 Building and Flying: ─The infrastructure ─A decade of MCM product development Looking into the Future Objectives

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 3 Man-Made & Mother Nature’s Threats Have Become Reality Since 9/11

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 4 Medical Countermeasures AntimicrobialsDiagnosticsVaccines Medical Devices Therapeutics

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 5 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.

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 6 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. Public Health Emergency Medical Countermeasures Enterprise PHEMCE COORDINATED PLANNING & EXECUTION ASPR/ BARDA NIH CDC and ASPR/OPEO R & DAdvanced Development Acquisition & Stockpiling Storage/ Maintenance Deployment & Recovery FDA CDC/SNS BARDA ASPR/ OPP RequirementsEvaluation CDC ASPR FDA BARDA CDC/SNS National Biodefense Science Board

ASPR: Resilient People. Healthy Communities. A Nation Prepared. BARDA Organization Director Dr. Robin Robinson Principal Deputy Director Dr. Carol Linden Chief Medical Officer & Deputy Director Dr. Richard Hatchett CBRN Director Dr. Gerald Kovacs Deputy Director Dr. Gary Disbrow Pandemic Influenza Director Dr. Robert Huebner Deputy Director Dr. Rick Bright Regulatory and Quality Affairs Director Dr. Debra Yeskey Clinical Studies Dr. Jo Schweinle, Director Strategic Science & Technology Dr. Jonathan Seals, Director Analytical Decision Support Dr. Tim Lant, Director Manufacturing, Facilities and Engineering Tom Warf. Director

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 9 9 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.

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 10 Regulatory and Quality Affairs is a BARDA Core Service. 10 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 TBD 2006

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 11 RQA Support 11 We provide BARDA and our Sponsors comprehensive capabilities in regulatory affairs and quality monitoring.

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 12 Building and Flying: a decade of MCM product development

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 13 BARDA ($2.0 B) NIH ($15.6 B) 3-7 yr yr 1-2 yr yr yr 1-2 yrs TIME $100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20M PIPELINE PHASE COST Valley of Death BARDA Bridges the MCM “Valley of Death” to Reduce Cost, Time, && Risk

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 14 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…

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 15 BARDA Created a Robust & Productive MCM Development Pipeline More than 150 MCM product candidates in development since 2004 PAHPA PBS MCM Review PAHPRA H7N9 H1N1 H5N1

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 16 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)

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 17 BARDA Delivered New MCMs under Project BioShield Botulism Anthrax Smallpox Radiation

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 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 Flucelvax Licensed 11/20/12 H5N1 vaccine Licensed 2007 Q-PAN H5N1 Vax BLA submitted 2012

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 19 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 20 Recently FDA Approved BARDA-supported MCMs Novartis Protein Sciences Recombinant-based Influenza Vaccine Anthrax Antitoxin HGS/GSK Botulinum Antitoxin Cangene Covidien Next-Gen Portable Ventilators Cell-based Influenza Vaccine Flu/RSV POC Diagnostic 3M/Focus

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 21 Looking into the Future

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 22 BARDA’s Core Services 22 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 TBD 2006

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 23 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 24 BARDA Assists MCM Developers Directly with Product Development & Manufacturing

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 25 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 26 MULTIFUNCTIONAL Glaxo-Smith Kline: Broad spectrum antibiotics Using Other Transaction Authority Agreement BARDA Prioritizes Repurposed and Multipurpose MCM Candidates REPURPOSED Romark: Nitazoxanide FDA-Approved for parasitic infections Under development for influenza, & MERS-Cov

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 27 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. 28 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

ASPR: Resilient People. Healthy Communities. A Nation Prepared. In the End… 29 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.