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 CBER’s 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 CBER’s 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. 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

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 FY11 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 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)

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

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

16. 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

17. 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

18. 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

19. 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

20. Looking Forward 2014: Moving to White Oak Campus

21. 21 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 PI’s  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

22. 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!