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

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

3. CBER Strategic Plan for Regulatory Science Follows CBERs 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 Advance regulatory science and research Manage for organizational excellence CBER Strategic Plan FY2012-2016: http://www.fda.gov/downloads/aboutfda/centersoffices/cber/ucm266867.pdf CBERs Strategic Plan for Regulatory Science and Research: http://www.fda.gov/downloads/BiologicsBloodVaccines/ScienceResearch/UCM303542.pdf

4. CBER Vision for Regulatory Science and Research Proactive and anticipatory of regulatory and public health issues Responsive to emerging public health and regulatory issues Collaborative, highest quality and relevance, and integral to our regulatory mission and public health portfolio Provide CBER with scientific expertise, tools, and data to support science-based decision- making and policy development

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

6. CBER Research Facilities Biotechnology Core Facility –Illumina HiSeq and MiSeq and bioinformatics support (HIVE) –Oligonucleotide, siRNA, PNA, and peptide synthesis –Peptide and DNA sequencing (ABI, capillary) –Taqman probe synthesis –HPLC; Capillary electrophoresis –Mass Spectrometry/Proteomics –Amino acid analysis Core support for –Flow Cytometry: Sorting/Analytic –Confocal microscopy –Microarray Vivarium with procedure rooms –Rodents, NHP, BSL-2 capacity for infectious agents BSL-3 and ABSL-3 laboratories

7. Scientific Expertise Novel technologies: NMR, mass spec, flow cytometry, microarray, high throughput sequencing and related bioinformatics/IT Microbiology: parasitology, bacteriology, virology Immunology Biochemistry and molecular biology Cell and developmental biology Epidemiology, meta-analyses of large healthcare databases Biostatistics

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

9. CBER Advances Regulatory Science through External Collaborations Data from FY13 CBER Research Reporting Database

10. 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

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

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

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

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

15. Office of Vaccines Research and Review Director Marion Gruber, Ph.D. Deputy Director Philip Krause, M.D. Office of Vaccines Research and Review Director Marion Gruber, Ph.D. Deputy Director Philip Krause, M.D. Associate Director for Research Konstantin Chumakov, Ph.D. Associate Director for Medical Policy and Vaccine Safety Karen Farizo, M.D. Associate Director For Management and Scientific Affairs Erik Henchal, Ph.D. Associate Director for Regulatory Policy Theresa Finn, Ph.D. Division of Bacterial, Parasitic and Allergenic Products Director: Jay Slater, M.D. Deputy: Drusilla Burns, Ph.D. Division of Bacterial, Parasitic and Allergenic Products Director: Jay Slater, M.D. Deputy: Drusilla Burns, Ph.D. Division of Viral Products Director: Jerry Weir, Ph.D. Deputy: Robin Levis, Ph.D. Division of Viral Products Director: Jerry Weir, Ph.D. Deputy: Robin Levis, Ph.D. Division of Vaccines and Related Products Applications Director: Wellington Sun, Ph.D. Deputy: Loris McVittie, Ph.D. Division of Vaccines and Related Products Applications Director: Wellington Sun, Ph.D. Deputy: Loris McVittie, Ph.D. To protect and enhance the public health by assuring the availability of safe and effective vaccines, allergenic extracts, and other related products. OVRR Mission Statement:

16. OVRR Regulatory Portfolio Bacterial vaccines (inactivated) – 10 Bacterial vaccines (live attenuated) – 2 Viral vaccines (inactivated) – 10 Viral vaccines (live attenuated) – 15 Combination products (inactivated) – 4 Allergenic extracts (diagnostic and therapeutic) >2,000 Live biotherapeutic products – INDs only

17. OVRR Core 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

18. OVRR Regulatory Challenges Emphasis on SAFETY: –Products for mass use (often universal) –Recipients are healthy individuals, often children Short regulatory cycle –Seasonal influenza vaccines –Response to emerging pathogens (pandemic vaccines) Many products are old –Innovative technologies Research plays a critical role in regulation of vaccines

19. The purpose of OVRR research: Contribute to regulation of vaccines and related products by addressing scientific aspects of critical regulatory issues Develop and maintain a scientific base for establishing methods and standards designed to ensure the continued safety, purity, potency and effectiveness of vaccines and related products Recruit and maintain highly trained scientists who possess the expertise necessary for review of regulatory submissions and development of regulatory policies and guidance documents Provide scientific expertise and leadership to vaccine industry to facilitate the development and introduction of new vaccines and related products

20. OVRR Research Priorities Safety To study factors affecting safety of regulated products, create and validate appropriate methods and standards Efficacy To study biomarkers and introduce new methods and standards to evaluate and improve vaccine efficacy Availability To develop new concepts and methods opening novel regulatory pathways to improve availability of vaccines and related products

21. OVRR Research Management Committee Coordinates research management process Division Directors and Deputies Two representatives from each research Division Representatives from review Division Office ADR Periodically reviews research priorities Identifies gaps and unnecessary redundancies Ensures uniform approach to allocation of resources

22. Annual Program Review Cycle Senior Investigator Lab Chief Division Director Research Management Committee Office IOD

23. 23 Looking Forward 2014: Moving to White Oak Campus

24. 24 White Oak Lab Facility State-of-the-Art Vivarium Imaging facility with MRI, digital X-ray, IVIS, ultrasound Transgenic derivation facility Expanded Space for Core Technologies: Flow cytometry Confocal microscopy High throughput sequencing and bioinformatic support 10 BSL-3 suites Designed to support work of at least 12 infectious agents and work of 36 PIs Many suites with capacity for animal holding rooms 1 suite to support sterile sorts and live cell confocal microscopy on BSL-3 agents Insectariums (BSL-2 and BSL-3) Suites designed to support Microarray and PCR Expanded NMR facility and Mass Spec Suites

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