OCTGT Overview Celia M.Witten, Ph.D., M.D. Director, Office of Cellular, Tissue, and Gene Therapies CTGTAC Meeting July 26, 2007

Topics  Mission and organizational structure  Regulatory scope  Research in OCTGT

OCTGT Mission Facilitate development of, approval of, and access to safe and effective medical products Facilitate development of, approval of, and access to safe and effective medical products cell therapy for cardiac repair immune attack and immunogenicity retrovirus

OCTGT Structure

Division of Cellular and Gene Therapies Raj Puri, Ph.D., M.D., Division Director Kimberly Benton, Ph.D., Deputy Director Tumor Vaccines and Biotechnology Branch Raj Puri, Ph.D., M.D., Chief* Cell Therapies Branch Keith Wonnacott, Ph.D., Chief Gene Therapies Branch Daniel Takefman, Ph.D., Chief Gene Transfer and Immunogenicity Branch Eda Bloom, Ph.D., Chief *Acting Cellular and Tissue Therapy Branch Steven Bauer, Ph.D., Chief*

Products Regulated by OCTGT  Cellular therapies  Gene therapies  Tumor vaccines and immunotherapy  Tissue and tissue-based products  Xenotransplantation products  Combination products  Devices used with cells/tissue

OCTGT regulatory portfolio and activities  Over 1100 active INDs, IDEs, and master files, several thousand amendments/year, consult reviews  One licensed product, a growing number of products in phase 3  Devices: 510ks, PMAs, HDEs  Tissue regulations  Pre-INDs, pre-pre-IND advice  Advisory committee meetings  Inspections  Enforcement actions

Additional OCTGT regulatory portfolio and activities  Partnerships: National Toxicology Program, NIH, CDC, NCI/IOTF program, NIH stem cell task force, NIST, MATES  Participation in international harmonization (ICH), WHO  Outreach talks at conferences, academic institutions, consumer and patient advocacy group meetings  Liaison activities with professional groups  Publication of papers on regulatory topics

Guidance Update Draft Guidance for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage 7/6/07 Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics 5/15/07 Guidance for Industry: Eligibility Determinations for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products 2/27/07 Draft Guidance for Industry: Minimally Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematological Malignancies 1/16/07

Roles and work of researcher- reviewers  Product application review, policy and guidance development, regulatory outreach, regulatory mentoring, advisory committee preparation, enforcement, international activities  Research, training/mentoring  Administrative work: branch chief duties, CBER peer review and coordinating committees, research management  Grant writing  Participation in the scientific community: scientific talks, chairing of conference sessions, editing, peer reviewing manuscripts and grant applications

Contributions of GTIB investigators Responsible for product review of 183 INDs (59 original submissions and over 2000 amendments), 10 BLA supplements Lead on three guidance documents, participation on others 7 regulatory publications 29 peer-reviewed research publication Journals include Gene Therapy, Molec. Therapy, J. Virol., PNAS, Vaccine, J. Infect. Dis., Emerg. Infect. Dis., Xenotrans.,Cell. Imm., J. Exp. Med., Antiox.Redox.Signaling 7 research-related review articles or book chapters Service on CBER committees, including Promotion and Conversion Evaluation Committee, two members, one serving as chair Service as Associate Director for Research Since the 2003 Site Visit

Approach to 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

Research Strategy in OCTGT  OCTGT products are diverse and rapidly evolving. They require new regulatory paradigms which are developing rather than established  Critical Path: fill gaps, deal with scientific challenges, figure out what is important  Sponsors study individual products, results often proprietary  CBER scientists perform studies relevant to entire product classes, make results public, and thus accessible to all sponsors, to advance the entire field

Current OCTGT Research Areas Virology Retroviruses, adeno, herpes, filo Immunology Anti-viral immunity, immunobiology of cell therapy and xenotransplantation Cell biology Control of differentiation in animal models, stem cell biology Cancer biology Molecular biomarkers, animal models Biotechnology Genomics, flow cytometry, proteomics Genomics, flow cytometry, proteomics

Reference Materials  Retrovirus reference material  Adenovirus reference material  RNA spike-in controls  Fluorescent standard solution  Fluorescent microbead standard

...for reviewing OCTGT/DCGT/GTIB research programs and providing input....for reviewing OCTGT/DCGT/GTIB research programs and providing input. Thank you