1. 1 Overview of the Division of Viral Products February 28, 2014 VRBPAC Discussion of the August 28, 2013 Site Visit for the Laboratory of Respiratory Viral Diseases Jerry P. Weir, Ph.D., Director Division of Viral Products/OVRR/CBER/FDA

2. 2 Division of Viral Products Office of Vaccines Research and Review Jerry P. Weir, Ph.D., Director Robin Levis, Ph.D., Deputy Laboratory of Hepatitis Viruses Marian Major, Ph.D., Acting Chief Laboratory of Vector-Borne Viral Diseases Lewis Markoff, M.D., Chief Laboratory of Retroviruses Hana Golding, Ph.D., Chief Laboratory of DNA Viruses Keith Peden, Ph.D., Chief Laboratory of Respiratory Viral Diseases Jerry Weir, Ph.D., Acting Chief Laboratory of Immunoregulation Carol Weiss, M.D., Acting Chief Laboratory of Method Development Konstantin Chumakov, Ph.D., Chief

3. 3 Division of Viral Products Mission and Functions Regulate viral vaccines and related biological products, ensuring their safety and efficacy for human use Facilitate the development, evaluation, and licensure of new viral vaccines that positively impact the public health

4. 4 Division of Viral Products Major Responsibilities Investigational New Drug (IND) and Biologics License Application (BLA) review, and other pre-marketing activities (e.g., pre-IND) BLA supplement review, lot release review, and other post-marketing activities (e.g., Biological product deviations) Manufacturer inspections (pre- and post-licensure) Consultation with other public health agencies (e.g., WHO, CDC, NIBSC) Conduct research related to the development, manufacturing, evaluation, and testing of viral vaccines

5. 5 The Role of Research in the Division of Viral Products Research and laboratory activities complement the regulatory mission Address issues related to regulated viral vaccines Anticipate and address issues related to the development and evaluation of new viral vaccine products General issues applicable to many products or product classes (e.g., cell substrate issues, improved test methods, etc.) Specific product issues (correlates of protection necessary for efficacy evaluation, animal models necessary for animal rule implementation, etc.)

6. 6 Division of Viral Products Staff & Budget Overview Division Staff – FY13 – –75 FTEs – –~ 40-50 contractors (ORISE) Postdoctoral fellows Postbac students Supported by targeted funds/external grants & contracts Division Budget – FY13 – –Standard operating budget ~ $2,800,000 – –Targeted CBER support ~ $2,200,000 Pandemic Influenza, Modernizing Science & Critical Path – –Medical Countermeasures ~ $3,000,000 – –External DVP funds ~ $3,700,000

7. 7 Division of Viral Products Staff (FTEs) - by Laboratory DVP IOD – 7 Respiratory Viral Diseases – 15 Hepatitis Viruses – 6 Retrovirus Research – 10 DNA Viruses – 16 Vector-borne Viral Diseases – 4 Method Development – 14 Immunoregulation – 6

8. 8 Site Visit Evaluation Program review Assessment of progress on projects pursued since previous site visit Individual review Consideration for promotion and tenure Evaluation of future directions

9. 9 Overview of the Laboratory of Respiratory Viral Diseases

10. 10 Organization of the Laboratory Chief (Acting) – Jerry Weir, PhD, Director, Division of Viral Products 4 Research Teams Influenza Virus Molecular Biology Zhiping Ye, M.D., Ph.D., Team leader Influenza Pathogenesis and Immunity Maryna Eichelberger. Ph.D., Team Leader Antigenic Structure and Function Team Judy Beeler, M.D., Team Leader Influenza B Viruses and Vaccine Seeds Jerry Weir, Ph.D., Acting Team Leader

11. 11 Regulatory Review Responsibilities Product review for viral vaccines Influenza virus vaccines Respiratory syncytial virus Parainfluenza virus types 1, 2 & 3 Human metapneumoviruses Measles, mumps, rubella, and varicella Clinical review for viral vaccines Vaccine lot release (protocol review) Manufacturers inspections (pre- & post-licensure) Participate and make presentations to the Vaccines Advisory Committee on influenza product issues and vaccine strain selection

12. 12 Regulatory Review Workload 13 scientists in LRVD have regulatory review responsibilities Pre-INDs43 IND files119 INDs amendments>500 BLAs & supplements188

13. 13 Other Regulatory and Public Health Responsibilities of the Laboratory Antigenic testing of manufacturers influenza virus seeds Preparation of reagents for seed testing Maintenance of influenza virus strain repository Seasonal strains for seed testing Candidate pandemic influenza vaccine strains Preparation of potency reagents for testing candidate pandemic influenza vaccines Selection and recommendation of strains for seasonal influenza vaccines 1 of 4 WHO Essential Regulatory Laboratories Serological analysis of vaccine responses for NH and SH vaccine selection

14. 14 Other Public Health Responsibilities (Continued) Participation in working groups and consultations with other public health agencies and vaccine stakeholders (selected examples) WHO – Influenza guidance for pandemic preparedness; Production and control of influenza vaccine manufacturing; Improving influenza vaccine strain selection; Influenza vaccines for broad immunity CDC ACIP – Febrile seizures & MMRV vaccination Vaccine manufacturers associations (PhRMA, IFPMA) – Annual Influenza Vaccine Workshops

15. 15 Laboratory of Respiratory Viral Diseases Research Program Research complements and supports the regulatory mission of ensuring the safety and efficacy of respiratory viral vaccines and facilitating the development of new viral vaccines Examples of issues addressed by the Laboratory’s research program Development of new assays to improve vaccine evaluation RSV neutralization Measles neutralization Influenza neuraminidase inhibition

16. 16 Laboratory of Respiratory Viral Diseases Research Program (Continued) Methods to improve vaccine manufacturing Development & evaluation of vaccine candidates to improve yields of influenza A and influenza B vaccines Evaluation of cell lines (MDCK) to improve influenza virus propagation Influenza vaccine potency Preparation of reagents to standardize vaccine testing RSV serology Influenza vaccine potency Elucidating the correlates of protection to facilitate vaccine efficacy evaluation RSV and influenza

17. 17 Research Program Support Each research team has received substantial support for its research program from internal (FDA) and external (non- FDA) sources External support emphasizes the public health significance of the Laboratory’s research program NIH Division of Microbiology and Infectious Diseases RSV reagent preparation and serological assay development CDC Serological assays to evaluate immune responses to measles vaccine Biomedical Advanced Research and Development Authority (BARDA) Methods to expedite influenza vaccine reagent calibration Methods to improve influenza vaccine potency measurement Development of improved influenza vaccine strains

18. 18 Site Visit Presentations August 28, 2013 Vladimir Lugovtsev Zhiping Ye Ewan Plant Xianghong Jing Hang Xie Maryna Eichelberger Hongquan Wan Judy Beeler