1. Center for Biologics Evaluation and Research FDA Overview Site Visit Carolyn A. Wilson, Ph.D. Associate Director for Research

2. CBER’s 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.

3. CBER Regulates Complex Products

4. CBER Organization

5. 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

6. CBER Strategic Plan for Research and Regulatory Science Regulatory Science: Development and use of the scientific knowledge, tools, standards, and approaches necessary for the assessment of medical product safety, efficacy, quality, potency, and performance. CBER intends to participate fully in this initiative as it develops http://www.fda.gov/downloads/BiologicsBloodVaccines/ScienceResearch/UCM303542.pdf

7. 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

8. CBER Mission: Role of Research Regulatory Challenge Challenge Public Health Novel Product CBERResearch Discovery New Tools RegulatoryPolicy/Decision LicensedProduct Improved Data – Benefit/Risk +

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

10. CBER Research Facilities Biotechnology Core Facility –Oligonucleotide, siRNA, PNA, and peptide synthesis –Peptide and DNA sequencing (Illumina, soon!) –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

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

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

13. Annual Review of Research

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

15. Research Career Paths PCE Senior Staff Fellow (Visiting Scientist) Senior Staff Fellow (Visiting Scientist) Site Visit 7 years Senior Investigator PCE Staff Fellow (Visiting Associate) Site Visit 4+3 years ORISE Fellow Pre and Post-Doctoral Up to 5 years ORISE Fellow Pre and Post-Doctoral Up to 5 years Temporary Permanent Staff Scientist PCE: Promotion, Conversion and Evaluation Committee Independent Scientist Support Scientist

16. Site-Visit Report, Content For each investigator reviewed, Evaluation of the relevance and quality of science New research directions and approaches to be considered Needed laboratory expertise Changes in laboratory organization New collaborations Specific comments on Laboratory Program and Management issues Specific comments on Personnel issues –Conversion Potential –Promotion Potential/Cyclical Review for Progress

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. OCTGT Mission Facilitate development of, approval of, and access to safe and effective CTGT products

19. OCTGT Mission Evaluate investigational new drug, device, biological license; pre-market applications for OCTGT products Protect subjects from infectious disease transmission from tissue transplantation. Strongly committed to partnership between FDA, government agencies, industry, patient advocates, scientists, and the public to promote and develop new therapies for the 21st Century, while protecting human subjects and maximizing biological product safety Plan and conduct FDA’s Mission relevant research to support development of cutting edge medical products

20. Products Regulated by OCTGT  Cellular therapies  Tumor vaccines and immunotherapy  Gene therapies  Tissue and tissue-based products  Xenotransplantation products  Combination products  Devices used for cells/tissues  Cord blood  Donor screening tests for use with cadaveric blood samples

21. CBER Office of Cellular, Tissue, and Gene Therapies Office of the Director Celia M.Witten, Ph.D., M.D., Director Stephanie Simek, Ph.D. Deputy Director Suzanne Epstein, Ph.D. Associate Director of Research Richard McFarland, M.D., Ph.D., Associate Director of Policy Division of Cellular and Gene Therapies Raj Puri, M.D., Ph.D., Director Kimberly Benton, Ph.D., Deputy Director Division of Human Tissues Ellen Lazarus, M.D., Director Division of Clinical Evaluation and Pharmacology/Toxicology Wilson Bryan, M.D., Director Mercedes Serabian, MS., Pharm/Tox Branch Chief

22. OCTGT regulatory portfolio and activities  Over 1325 active INDs and IDEs, over 5000 INDamendments in 2012, plus consult reviews  Seven licensed products, a growing number of IND products in advanced development  Devices: 510ks, PMAs, HDEs  Tissue regulations  Pre-INDs, pre-pre-IND advice  Policy and guidance, advisory committee meetings  Inspections, regulatory site visits  Enforcement actions, international activities

23. Guidance Examples  Potency testing for cell and gene therapies  Therapeutic cancer vaccines  Allogeneic pancreatic islet cell products  Cell therapy for cardiac disease  Products to repair or replace knee cartilage  Cord Blood  Good Tissue Practices  International Harmonization on Genomic Biomarkers

24. Additional DCGT regulatory portfolio and activities Partnerships: National Toxicology Program, NIH, CDC, NCI/IOTF program, NIH stem cell task force, NIST, MATES, TERMIS, ASTM Participation in ICH (international conference on harmonization), WHO Outreach talks at conferences, academic institutions, consumer and patient advocacy group meetings Liaison activities with professional groups Publication of manuscripts on regulatory topics OCTGT Learn webinar series on product manufacturing and testing, clinical, and preclinical topics. See http:// www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

25. OCTGT research: Stay ahead of the curve as products and technologies evolve  For this wide spectrum, cannot have research related to each product.  If research addressed only the products and assays of today, we would already be obsolete. We must guide pre-IND work, prepare the way for anticipated products.

26. OCTGT Research Strategy OCTGT products are diverse and rapidly evolving. They use new regulatory paradigms, developing rather than established  Fill scientific gaps, deal with barriers  Perform studies relevant to entire product classes (sponsors study individual products)  Make results public, and thus accessible to all sponsors, to advance the entire field  Perform horizon scanning to choose priorities Scientific areas emphasized will be covered in the Division Director summary

27. 2012 OCTGT Research Priorities 1.Chemistry, manufacturing, controls: Development and evaluation of methods and standards for improved product characterization and lot release testing, including definition of product markers predictive of safe, effective, and consistent product performance. 2.Pharmacology, toxicology, product rationale: Development and evaluation of preclinical/nonclinical in vitro and in vivo methods and studies informative about the safety and efficacy of OCTGT products. 3.Participation in CBER-, FDA-, and DHHS-wide initiatives including risk assessment, clinical trial design and monitoring, development of biomarkers identification of characteristics predictive of product performance, counterterrorism, pandemic influenza preparedness, and HIV/AIDS programs, nanotechnology, and efforts to reduce, refine, and replace the use of animals (3Rs), as well as OCTGT-specific initiatives in these areas. 4.Improvement of the microbial safety of human tissue products by development and evaluation of methods for better processing conditions, pathogen inactivation, and/or pathogen detection.

28. 2012 OCTGT Research Priorities 1.Chemistry, manufacturing, controls: Development and evaluation of methods and standards for improved product characterization and lot release testing, including definition of product markers predictive of safe, effective, and consistent product performance. 2.Pharmacology, toxicology, product rationale: Development and evaluation of preclinical/nonclinical in vitro and in vivo methods and studies informative about the safety and efficacy of OCTGT products. 3.Participation in CBER-, FDA-, and DHHS-wide initiatives including risk assessment, clinical trial design and monitoring, development of biomarkers identification of characteristics predictive of product performance, counterterrorism, pandemic influenza preparedness, and HIV/AIDS programs, nanotechnology, and efforts to reduce, refine, and replace the use of animals (3Rs), as well as OCTGT-specific initiatives in these areas. 4.Improvement of the microbial safety of human tissue products by development and evaluation of methods for better processing conditions, pathogen inactivation, and/or pathogen detection.

29. Thank you to the site visitors for reviewing CBER research programs and providing your insights.

30. 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!