1. Center for Biologics Evaluation and Research Carolyn A. Wilson, Ph.D. Associate Director for Research Applying Regulatory Science to Advance Development of Innovative, Safe and Effective Biologic Products

2. CBER 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; and help to defend the public against the threats of emerging infectious diseases and bioterrorism

3. CBER Regulates Complex Products XenotransplantationProducts Tissues Cell & Gene Therapies Blood, Blood Components and Derivatives Vaccines: Preventive & Therapeutic Related Devices Allergenic Products Therapeutic Probiotics

4. CBER Strategic Goals  Increase national preparedness to address threats from bioterrorism, pandemic and EIDs  Improve global public health through international collaboration  Enhance ability of science and technology to facilitate development of safe and effective biological products  Ensure safety of biological products  Advance regulatory science and research  Manage for organizational excellence CBER Strategic Plan FY2012-2016: http://www.fda.gov/downloads/aboutfda/centersoffices/cber/ucm266867.pdf

5. Regulatory Science: knowledge, tools, standards, and approaches Development and use of the scientific knowledge, tools, standards, and approaches necessary for the assessment of medical product safety, efficacy, quality, potency, and performance. FDA Strategic Plan for Regulatory Science http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm267719.htm

6. CBER Vision for Regulatory Science and Research Proactive, responsive, and collaborative Provide CBER with scientific expertise, tools, and data to support science-based decision making and policy development

7. Role of CBER Research CBER research occupies a well-defined critical niche at the end of product development pipeline CBER scientists are uniquely positioned to address scientific issues related to safety and efficacy of medicinal products The results remain in public domain and benefit the entire industry

8. Regulatory Challenge Challenge Public Health Novel Product RegulatoryScience Discovery New Tools RegulatoryPolicy/Decision LicensedProduct Improved Data – Benefit/Risk + Using Science and Regulation to Advance Product Development

9. CBER Organization Director Deputy Associates Management Compliance, Biologics Quality Communication, Outreach and Development Biostatistics and Epidemiology Cellular, Tissue, and Gene Therapies Vaccines Research And Review Blood Research And Review

10. CBER Research Facilities Biotechnology Core Facility –Oligonucleotide, siRNA, PNA, and peptide synthesis –Peptide and DNA sequencing –Taqman Probe synthesis –HPLC; Capillary electrophoresis –Mass Spectrometry/Proteomics –Amino acid analysis Core support for –Flow Cytometry: Sorting/Analytic –Confocal microscopy Vivarium with procedure rooms –Rodents, NHP, BSL-2 capacity for infectious agents BSL-3 and ABSL-3 laboratories

11. Scientific Expertise Novel technologies: NMR, mass spec, flow cytometry, high throughput sequencing, microarray Microbiology: –parasitology, bacteriology, virology Immunology Biochemistry and molecular biology Cell and developmental biology Biostatistics and epidemiology

12. CBER researcher = “Researcher-Regulator” ~20% CBER Staff Integration of research and review ensures Relevance, Expertise, Timeliness, and Usability

13. CBER Advances Regulatory Science through External Collaborations Data from FY11 CBER Research Reporting Database

14. Annual Review of Research PI provides For each project Progress report Future plans Budget Request Presentations, Pubs Other output Information reviewed Lab chief, DD, ADR, OD Relevance Productivity Quality Research Reporting Database Funding Allocated Relevance to priority Scientific/Reg Output Feasiblity

15. The purpose of research management To reconcile investigator-initiated research model with the needs dictated by FDA mission

16. Cyclic Peer Review of Every PI Every 4 Years External – Site Visits peer review by scientific experts Internal – Promotion, Conversion, Evaluation Committee

17. Site-Visit Report Draft report is distributed to full Advisory Committee Final report is approved by full Advisory Committee Final report used in many ways: –Internal peer review of research/PI by Promotion, Conversion, Evaluation Committee (PCE) for personnel actions –By PIs for improving research program –By management, resource allocation decisions may be impacted by report (pending resource availability)

18. Office of Vaccines Research and Review Slides Courtesy of Konstantin Chumakov, PhD Associate Director for Research, OVRR

19. OVRR Mission Statement Protect and enhance the public health by assuring the availability of safe and effective vaccines, allergenic extracts, and other related products.

20. OVRR Activities Review, evaluate, and take appropriate actions on INDs, BLAs, amendments and supplements to these applications for vaccines and related products, conducting inspections, etc. Develop policies and procedures governing the pre-market review of regulated products Conducting research related to the development, manufacture, and evaluation of vaccines and related products

21. OVRR Research Contributes to regulation of vaccines and related products by addressing scientific aspects of critical regulatory issues Develops and maintains a scientific base for establishing methods and standards designed to ensure the continued safety, purity, potency and effectiveness of vaccines and related products Recruits and maintains highly trained scientists who possess the expertise necessary for review of regulatory submissions and development of regulatory policies and guidance documents Provides scientific expertise and leadership to vaccine industry to facilitate the development and introduction of new vaccines and related products

22. OVRR Research Management Process Research Management Committee Division research portfolio Lab Chief Proposal Division Director Laboratory projects OVRR Budget projection Annual Research Plan CBER Principal Investigato r Current priorities Site visit, Advisory committee recommendations Regulator y Division Current regulatory issues

23. OVRR Rating of Research Projects PUBLIC HEALTH SIGNIFICANCE –Public health need — dealing with high priority issue –Immediate regulatory relevance — pending applications exist –Strategic regulatory relevance — resolving general regulatory challenge of major importance –Office/Division needs — fills a gap in the overall research program SCIENTIFIC MERIT –Scientific rationale –Originality and innovation –Feasibility of research approach –Budget (affordability) QUALIFICATIONS AND PRODUCTIVITY –Necessary qualifications –Past productivity of investigator/impact

24. Thank you! To the Site Visit reviewers and Advisory Committee Your input improves CBER’s research programs External review is critical to fulfilling our regulatory mission!