United States Department of Health & Human Services

1. 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

2. Boeing 747SP

3. Objectives • Building and Flying: • The infrastructure • A decade of MCM product development • Looking into the Future

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

5. Antimicrobials Diagnostics Vaccines Therapeutics Medical Devices Medical Countermeasures

6. 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.

7. PHEMCE Process: Threat Assessments to Medical Countermeasures • 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)

8. Public Health Emergency Medical Countermeasures Enterprise National Biodefense Science Board BARDA CDC/SNS CDC ASPR CDC and ASPR/OPEO ASPR/ OPP ASPR/ BARDA CDC/SNS BARDA NIH FDA FDA Requirements R & D Advanced Development Acquisition & Stockpiling Storage/Maintenance Deployment & Recovery Evaluation PHEMCE COORDINATED PLANNING & EXECUTION

9. BARDA Organization Manufacturing, Facilities and Engineering Tom Warf. Director Analytical Decision Support Dr. Tim Lant, Director Strategic Science & Technology Dr. Jonathan Seals, Director Clinical Studies Dr. Jo Schweinle, Director

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. 9 9

11. Regulatory and Quality Affairs is a BARDA Core Service. • Centers for Innovation in Advanced Development & Manufacturing 2012 • Regulatory & Quality Affairs • Fill Finish Mfg. Network 2006 2013 • ADS • Modeling • Hub • Nonclinical Network 2009 2010 • Clinical Studies Network • Strategic Innovations Portfolio 2013 TBD

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

13. Building and Flying: a decade of MCM product development

14. BARDA Bridges the MCM “Valley of Death” to Reduce Cost, Time, && Risk NIH ($15.6 B) BARDA ($2.0 B) Valley of Death 3-7 yr 0.5-2 yr 1-2 yr 2-3.5yr 2.5-4 yr 1-2 yrs TIME PIPELINE PHASE COST $100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20M

15. Fitting Regulatory into a Preparedness Paradigm… • 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…

16. BARDA Created a Robust & Productive MCM Development Pipeline • More than 150 MCM product candidates in development since 2004 MCM Review PAHPRA H7N9 H5N1 PAHPA H1N1 PBS

17. 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)

18. BARDA Delivered New MCMs under Project BioShield Smallpox Anthrax Radiation Botulism

19. BARDA Nurtured Influenza Vaccine Development to Achieve National Pan Flu Vaccine Goals Universal Vaccines Q-PAN H5N1 Vax BLA submitted 2012 Antigen-Sparing Vaccine Technology Recombinant-based Vaccines Cell-based Vaccines FluBlOk Licensed 01/16/13 Flucelvax Licensed 11/20/12 Egg-based Vaccines H5N1 vaccine Licensed 2007 “More and better vaccines sooner”

20. 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

21. Recently FDA Approved BARDA-supported MCMs Recombinant-based Influenza Vaccine Cell-based Influenza Vaccine Protein Sciences Novartis Anthrax Antitoxin Next-Gen Portable Ventilators Botulinum Antitoxin HGS/GSK Flu/RSV POC Diagnostic Covidien 3M/Focus Cangene

22. Looking into the Future

23. BARDA’s Core Services • Centers for Innovation in Advanced Development & Manufacturing 2012 • Regulatory & Quality Affairs • Fill Finish Mfg. Network 2006 2013 • ADS • Modeling • Hub • Nonclinical Network 2009 2010 • Clinical Studies Network • Strategic Innovations Portfolio 2013 TBD

24. BARDA Uses Public-Private Partnerships to Build Domestic MCM Manufacturing Capacity • Retrofitting Vaccine Manufacturing Infrastructure • Changing Flu Vaccine Industry sanofi pasteur – Swiftwater, PA Novartis – Holly Springs, NC

25. BARDA Assists MCM Developers Directly with Product Development & Manufacturing

26. BARDA Assists MCM Developers thru our Animal Models Network Battelle Pacific Northwest Division IIT Research Institute University of Illinois, Chicago Battelle Memorial Institute SRI International BioQUAL, Inc. Southern Research Lovelace Respiratory Research Institute Defence Science and Technology Laboratory, Porton Down MRIGlobal University of Texas Medical Branch Health Protection Agency, Porton Down

27. BARDA Prioritizes Repurposed and Multipurpose MCM Candidates REPURPOSED Romark: Nitazoxanide FDA-Approved for parasitic infections Under development for influenza, & MERS-Cov MULTIFUNCTIONAL Glaxo-Smith Kline: Broad spectrum antibiotics Using Other Transaction Authority Agreement

28. MCM Gaps for BARDA to Fill • 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

29. Current BARDA MCM Challenges • Implementing new strategies to repurpose & multipurpose MCMs • Developing sound utilization strategies and ConOps • Transfer of technologies to CIADM facilities • Qualifying new animal models

30. 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.