Overview of the Division of Viral Products Jerry P. Weir, Ph.D. Director Division of Viral Products/OVRR/CBER/FDA

Mission 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

Division of Viral Products 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 testing, 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

Licensed Viral Vaccines Hepatitis Viruses Hepatitis A Hepatitis B HepA/HepB HepB-Hib DTaP-HepB-IPV Vector-Borne Viral Diseases Yellow Fever Japanese Encephalitis Virus DNA Viruses Varicella Virus Smallpox Childhood Viruses Inactivated poliovirus Measles, Mumps, rubella Rotavirus Respiratory Viruses Inactivated Influenza Live attenuated influenza Other Viral Vaccines Rabies

Viral Vaccines Under Development Hepatitis Viruses Hepatitis C Hepatitis E Vector-Borne Viral Diseases Dengue West Nile Virus DNA Viruses Human Papillomavirus Herpes Simplex Cytomegalovirus New smallpox vaccines Childhood Viruses New Rotavirus vaccines HIV Respiratory Viruses New Influenza vaccines Pandemic influenza vaccines Respiratory Syncytial Virus Parainfluenza virus Vaccines for Emerging Diseases and agents of Bioterrorism Ebola and other hemorrhagic fevers Venezuelan Equine Encephalitis Virus and other encephalitis causing viruses

Division of Viral Products Snapshot 7 Laboratories 17 Tenured Principal Investigators 67 Full-time equivalent staff (April 2006) > 50 Contract staff (e.g., post-doctoral fellows) ~ 140 publications (last 2 years) > $3,000,000 grants and contracts (FY05) Researcher/Reviewer Model Review workload (e.g., INDs, BLAs, post-marketing) Mission-relevant research Outreach and collaboration (e.g., expert consultants to WHO)

Division of Viral Products Research Priorities Develop methods and models to assess and predict viral vaccine safety and efficacy development and evaluation of novel vaccination strategies and technologies identification of correlates of protection development of animal models predictive of efficacy Facilitate the development and evaluation of vaccines for high priority viral diseases including emerging diseases and agents of bioterrorism influenza vaccine reagent preparation issues related to vaccine development for high priority diseases (e.g., RSV, HepC), emerging diseases (e.g., pandemic influenza, HIV, West Nile virus) and Bioterrorism agents (e.g., smallpox) Evaluate novel approaches to improve vaccine quality evaluation of cell substrates Development and evaluation of new methods and assays for product characterization

Division of Viral Products Laboratories Jerry P. Weir, Ph.D., Director Phil Krause, M.D., Deputy Director Laboratory of Hepatitis Viruses Steve Feinstone, M.D., Chief Laboratory of Vector-Borne Viral Diseases Lewis Markoff, M.D., Chief Laboratory of Retroviruses Hana Golding, Ph.D, Chief Laboratory of DNA Viruses Andrew Lewis, M.D., Chief Laboratory of Respiratory Viral Diseases Chief - Vacant Laboratory of Immunoregulation Ira Berkower, M.D., Chief Laboratory of Methods Development Konstantin Chumakov, Ph.D., Chief

Laboratory of Vector Borne Viral Diseases Areas of Research Characterization of candidate live, attenuated dengue and West Nile virus vaccines. Mechanism by which flaviviruses repair attenuating 3'terminal deletions of genome RNA. Virion morphogenesis. Effect of quasi-species character on phenotype. Development of an ELISA-based potency assay for rabies vaccines.

Laboratory of Hepatitis Viruses Areas of Research Vaccine strategies to prevent HCV infection Development of mouse models for HCV infection to replace the chimpanzee Development of in vitro culture systems to study antibody neutralization of HCV Biomarkers for HCV protection and HBV/HCV related hepatocellular carcinoma

Laboratory of Immunoregulation Areas of Research Structure-function analysis of HIV envelope glycoproteins Vaccination strategies to enhance vaccine immunogenicity Dissecting the neutralizing antibody response to vaccinia virus gp120 particles HBsAg particles

Laboratory of Respiratory Viral Diseases Areas of Research Prepare and distribute influenza virus reagents to determine purity and strength of influenza vaccines Perform serology studies in support of influenza strain selection Develop new high growth influenza virus strains for vaccines and determine properties for optimal growth in eggs and tissue culture Evaluate new vaccine strategies Identify cellular receptors for respiratory syncytial virus (RSV) and determine antigenic structure of RSV glycoproteins Develop serological methods for vaccine trial evaluation

Laboratory of Method Development Areas of Research Microarrays and other molecular methods for analysis of pathogens Genotyping of viruses and bacteria Identification of Mycoplasmas Genetic stability of live viral vaccines Immunological test methods development New animal model development Neurotoxicity assay development

Laboratory of Retrovirus Research Areas of Research Development of assays for HIV and smallpox clinical trial evaluation Identification and characterization of adjuvants Activity and safety of DNA vaccines and CpG oligodeoxynucleotides Safety and evaluation of cell substrates used for vaccine production Retrovirus transmission

Laboratory of DNA Viruses Areas of Research Evaluation of cell substrates used for vaccine manufacture Developing methods to evaluate the risks posed by the use of neoplastic cells for production of viral vaccines Detection of adventitious agents Mechanisms of viral latency Immunogenicity and pre-clinical efficacy of new-generation smallpox vaccines Evaluation of novel herpesvirus vaccination strategies

Summary The research programs and laboratory activities in the Division of Viral Products support the regulatory mission of the Office of Vaccines and CBER Ensures the safety and efficacy of regulated viral vaccine products, and Facilitates the development and evaluation of new virus vaccine products