1. Division of Hematology Basil Golding M.D. Division Director Site Visits 2010 Laboratories of Hemostasis, and Plasma Derivatives

2. Division of Hematology PIs: 3 2 4 4 Total = 13 LBVB Biochemistry & Vascular Biology LCH Cellular Hematology LH Hemostasis LPD Plasma Derivatives CRB Clinical Review Branch Research/Review Units

3. PositionsLBVBLPDLHLCHCRBIOD Branch Chief 11111 PI 2341 Staff Scientist 1301 Staff Fellow 3104 Regulatory Scientist 15405 ORISE 1141 Biologist 1322 Medical Officer 000271 Adm. Staff 3 Total 1117151489 Grand Total = 74 – 7 ORISE = 67 FTEs

4. CBER Mission MISSION: To ensure the safety, purity, potency and effectiveness of biological products including vaccines, blood and blood products, and cells, tissues and gene therapies for the prevention, diagnosis, and treatment of human diseases, conditions or injury. Through our mission, we also help to defend the public against the threats of emerging infectious diseases and bioterrorism.

5. Division of Hematology Scope of Regulation and Research Research helps solve regulatory problems (Critical Path) and serves to enhance the expertise of scientific investigators who have review responsibility for these products Scientific evaluation of biologic products derived from blood include those –isolated from blood or plasma –analogous materials derived by recombinant DNA and transgenic technology Clinical applications include : –Prophylaxis and/or treatment of bleeding disorders –Trauma/shock –Infectious diseases –Immunological deficiencies –Replacement therapy in congenital or acquired plasma protein deficiencies –Counter-terrorism and pandemic preparedness

6. Division of Hematology: Regulatory Products and Process Applications and products: –Biologics, Drugs, and Devices –Diverse complex proteins and carbohydrate polymers Decisions - based on scientific data showing safety, efficacy and purity –decision-making process internal review meetings with manufacturers Consultations: CDER/CDRH, SGEs presentations to Advisory Committees workshops

7. Regulatory Process (cont’d) Evaluation process of products –scientific review –laboratory investigation if needed –lot release tests –standards are developed for lot release of different products and are often distributed as CBER and/or international standards –Surveillance Inspections Adverse Event Reports Product failures

8. Regulatory Workload Type of SubmissionNumber per Year BLA9 BLA-S214 510 (k)60 NDA7 NDA-S29 ANDA1 ANDA-S8 IND (Original = 24)76 Meetings108

9. Division of Hematology: Other Tasks Policy and Guidance documents Harmonization with other Countries and EMA Liaisons: Government Agencies (e.g. NIH, CDC) Regulatory agencies of foreign governments International bodies Consumer groups Non-profit organizations Industry Communications Websites Letters

10. Division of Hematology Research Research Topics –Protein therapeutics: Structure-function relationships –New tools for characterization: MS, aptamers, phage display libraries Immunogenicity: in silico, aptamers, animal models (KO/KI) Polymorphism: bioinformatics, optimize expression and function New assays: Thrombin generation, VWF, A1PI, C1-esterase inhibitor –Nanomaterials Biocompatability Microparticles/storage and adverse events

11. Division of Hematology Research –Infectious Disease prevention and treatment Ig for pandemic flu’ Neutralizing/interfering epitopes against HCV –Oxygen-carrying compounds –Red blood cells, plasma and platelets Storage lesions Pathogen reduction Lyophilized RBCs and platelets: in vitro function and in vivo survival, O 2 delivery Plasma: coagulation factor function

12. Research Budget Sources –Operating –OWH –NIH Intramural AIDS, BARDA, NVP –DARPA –Critical Path PI approx. (operating = 50 - 100K) (outside = 50-100K)

13. Budget Allocation: Project Ranking Research Elements –Mission Relevance –Public Health Impact –Productivity –Feasibility

14. Resources per PI: Summary Human –1 FTE –1 ORISE Budget –100K p.a. Space –1 module Time –50% or less

15. Research Output Papers –Approx. 2.5 per year per PI Guidance –2 per year Workshops –2 per year

16. Thanks