Review of Site Visit Report Laboratory of Molecular Virology DETTD/OBRR/CBER March 18, 2005 Hira L. Nakhasi, Ph.D. Director, DETTD

Immediate Office of the Director Hira Nakhasi, Ph.D. (Director) Paul Mied, Ph.D. (Deputy Director) Elliot Cowan, Ph.D., Assoc. Dir. Regulatory Affairs Charles Lucey, M.D. MPH, JD (Assoc. Dir. Medical Affairs) Carloyn Feemester (CS0) Division of Emerging and Transfusion Transmitted Diseases Laboratory of Molecular Virology Indira Hewlett, Ph.D. (Chief) HTLV, HIV, WNV Molecular Virology Immuno-pathogenesis Gene Regulation Laboratory of Hepatitis and Related Emerging Agents Gerardo Kaplan, Ph.D. (Chief) HBV, HCV, HAV Hepatitis Viral Regulation Hepatitis Viral Pathogenesis Laboratory of Bacterial, Parasitic, and Unconventional Agents David Asher, M.D. (Chief) TSE, Leishmania, Malaria TSE Pathogenesis, Detection Parasitic Pathogenesis Detection Product Testing Staff Robin Biswas, M.D. (Head) Lot release testing of Serological and Nucleic acid based kits: HIV, HTLV, Hepatitis B,C

Division of Emerging and Transfusion Transmitted Diseases (DETTD) Mission Plans and conducts basic and applied research –development, manufacture, pathogenesis and testing of blood borne Viral (HIV, HTLV, hepatitis, WNV), Parasitic (Leishmania, Malaria, Chagas), Bacterial, potential BT agents (Plague, Anthrax, Hemorrhagic viruses) and Transmissible Spongiform Encephalopathy agents or “prions”. Ensures the safety of Nation’s blood supply – by reviewing, evaluating and recommending actions BLAs, PMAs, INDs, IDEs, 510(k)s for blood screening and diagnostic testing for above mentioned agents. Develops and revises FDA Guidance for users of blood screening and diagnostic products.

Division of Emerging and Transfusion Transmitted Diseases (DETTD) Mission Performs lot-release testing for approval of investigational tests and of licensed products. Develops reference materials for lot-release testing. Performs inspections of manufacturers of licensed products, manufacturing facilities. Provides expert scientific and technical advice to other Agency and Government components. Presents issues related to the safety and efficacy of blood donor screening testing at the Blood Product Advisory Committee and TSE Advisory Committee meetings

Personnel and Budget FY ‘04 Total Staff58 Senior Investigators11 Biologists14 Staff Fellows7 Staff Scientists5 Regulatory Scientists13 Administrative Staff2 Post-doctoral Fellows6 Budget (FY 2004)~ $400,000 Published 41 original articles and book chapters

Regulatory Activities FY ‘04* Regulatory submissions IND/IDE (original); IND/IDE (amendments); BLA (original application); BLS (supplement); PMA PMA supplement; 510(k) (original); PMA/BLA Annual Reports Total374 Tested and released 1052 lots and performed 8 inspections and 2 laboratory investigations

Research Priorities I.Pathogenesis of Blood borne Viral, Bacterial and Parasitic agents: A.Pathogenesis of HIV, drug resistant HIV, genetic variants of HIV, HIV tat, HTLV, WNV B.HHV and other herpes infections in AIDS C.Pathogenesis of Malaria, Leishmania and Chagas diseases D.Pathogenesis of hemorrhagic viruses and bacterial agents used as bioterrorism agents E.Pathogenesis of HCV, HBV,HAV and other related Hepatitis viruses F.Pathogenesis of TSE (prion) and bacterial agents

Research Priorities continued….. II. Blood Donor Screening Test Development: A.Development of new technologies for detection of retroviruses in blood and body fluids including microarray, PERT and related methods. B. Identification and characterization of new HIV-1 and -2 variants: Impact on diagnostics, drug therapy and vaccine development C. Development of lot release panels and standards for blood borne agents (e.g. HIV, WNV, HCV, HBV) D.Development of pathogen chip using microarray DNA technology for screening of blood borne parasitic, bacterial, viral and bioterrorism agents (e.g. Hemorrhagic viruses, smallpox anthrax, Tularemia, and plague). E.Development of detection and validation methods for TSE agents F.Develop and optimize PCR based, rapid and reliable methods to detect bacterial agents in blood

Critical Path Initiatives 1.Standards for West Nile virus testing 2.Smallpox and blood safety 3.HIV surveillance in Cameroon 4.Relative sensitivity of HBsAg tests and HBV NAT 5.Development of oligonucleotide based microarray detection multiplex system for viral, bacterial and parasitic blood borne pathogens 6.Development of proof of concept for new vaccine strategies for parasitic and viral agents

Counter Terrorism Initiatives Develop laboratory expertise in new technologies Utilize this expertise for evaluation of related submissions from industry Transfer technology for industry development Lot-release testing Understand the molecular mechanisms of pathogenesis of BT agents in blood

Thank You