1. 1 Overview: Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies Raj K. Puri, M.D., Ph.D. Director, DCGT Office of Cellular, Tissue and Gene Therapies FDA, CBER CTTB Site Visit Report to CTGTAC February 10, 2012

2. 2 Outline  Organization  Mission and Activities  Regulatory Scientist and Researcher Reviewer Model  DCGT Research Projects

3. 3 CBER Office of Cellular, Tissue, and Gene Therapies (OCTGT) 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

4. 4 Division of Cellular and Gene Therapies (DCGT) Raj Puri, M.D., Ph.D., Division Director Kimberly Benton, Ph.D., Deputy Director Cellular and Tissue Therapy Branch Steven Bauer, Ph.D., Chief Tumor Vaccines and Biotechnology Branch Raj Puri, M.D., Ph.D. Chief Cell Therapies Branch Keith Wonnacott, Ph.D., Chief Gene Therapies Branch Daniel Takefman, Ph.D., Chief Gene Transfer and Immunogenicity Branch Andrew Byrnes, Ph.D., Chief

5. 5 OCTGT Regulated Products  Cellular therapies  Tumor vaccines and immunotherapy  Gene therapies  Tissue and tissue based products  Xenotransplantation products  Combination products  Devices used for cells/tissues  Donor screening tests (for use with cadaveric blood samples)

6. 6 Mission  Evaluate investigational new drug, device, biological license, and pre-market applications for OCTGT products  Protect patients 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

7. 7 OCTGT regulatory portfolio  Over 1260 active INDs and IDEs, over 5000 IND amendments in 2011, plus consult reviews  Four 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  Enforcement actions, international activities

8. 8 DCGT Activities Ensure the safety of cellular, gene therapy and other products through:  Development and implementation of a comprehensive risk- based regulatory framework  Evaluation of new technologies for product characterization and rapid assessment of product safety  Development of FDA Policies and Guidances for the regulation of cellular and gene therapy and other products

9. 9 DCGT Activities continued..  Inspections:  of manufacturing facilities, regulatory site visits  Consultation and Education:  Provide scientific and technical advice to other CBER Offices, FDA Centers, and Government Agencies  Information sharing and discussion with sponsors  Counterterrorism:  COOP Coordination and Laboratory Red Alert Plan  Participation in FDA’s CT exercise/simulations

10. 10 DCGT Activities continued.. Community Outreach: (seminars, panel discussions, round table, workshops)  Cell Therapy including stem cell  Tumor Vaccines and Immunotherapy  Gene Therapy  Tissue Engineering  Xenotransplantation  Round Table (CIRM, JDRF, ARM)  OCTGT Learn Webinar Series

11. 11 DCGT Activities continued.. Partnerships:  Development of Retrovirus and Adenovirus reference material  ASTM representation and STR profiling for cell line authentication  Workshops in collaboration with NIH “Pluripotent Stem Cells in Translation: Early Decisions” (March 21-22, 2011)  MOU with NIH NINDS and NHLBI for sharing of information and expertise; collaboration with CRM  ERCC and Fluorescence standards for microarray and flow technologies  Inter Agency Oncology Task Force between NCI and FDA for joint fellowship training program

12. 12 Current DCGT Research Areas  Virology  Retroviruses, adenovirus  Immunology  Immune responses to viral and plasmid vectors,  autoimmunity and immune regulation  Cell and developmental biology  Control of differentiation in animal models:  cell fate and survival, stem cell biology  Cancer biology  Molecular biomarkers, cancer vaccines, animal models  Biotechnology  Genomics, flow cytometry, proteomics, transgenics  Microbiology of tissue safety  Pyrosequencing and whole genome sequencing

13. 13 Researcher Reviewer Model  Cellular, tissue engineering, and gene therapies evolve rapidly and continually present new regulatory challenges  These novel products raise extraordinarily complex issues  DCGT seeks to foster a cadre of Researcher Reviewer scientists who :  perform regulatory review and identify Critical Path research needs to enhance and promote product development and patient safety  perform research in key areas to support the FDA mission and help sponsors solve product development problems to advance cellular, gene therapy and other products to the market place

14. 14 Types of Researcher Reviewers  Principle investigators (PIs) – tenured or tenure track researcher reviewers  Staff Scientists – tenured researcher reviewers supporting PIs program: do both review and research  Technicians: do primarily research, some do limited review work  Staff Fellows: do both review and research work  Postdoctoral fellows funded as ORISE: do primarily research Note: Resources are provided to PIs

15. 15 Responsibilities of PIs Product review INDs, IDEs, PMA, 510k, HDEs, licenses, master files, inspections - regulatory mentoring by branch chiefs Policy development working groups, guidance development, advisory committees Outreach presubmittal advice, scientific and regulatory talks, refereeing and editing for journals, chairing sessions at scientific conferences, scientific collaborations relevant to the regulatory science Research lab management, training/mentoring/supervising, publishing papers, grant writing, leveraging/collaboration

16. 16 Research Assessment/Management  Site visit and CBER Advisory Committee recommendations  Promotion and Conversion Evaluation (PCE) Committee review  Regulatory workload and quality  Publications (including guidance documents, research articles and regulatory articles)  Success in securing external funding

17. 17 Thank you