OCTGT OverviewOCTGT Overview

Celia M.Witten, Ph.D., M.D.Celia M.Witten, Ph.D., M.D.

Director, Office of Cellular, Tissue, and Gene Director, Office of Cellular, Tissue, and Gene TherapiesTherapies

CTGTAC MeetingCTGTAC Meeting

July 26, 2007July 26, 2007

TopicsTopics

Mission and organizational structure

Regulatory scope

Research in OCTGT

OCTGT MissionOCTGT Mission Facilitate development of, approval of, and Facilitate development of, approval of, and access to safe and effective medical productsaccess to safe and effective medical products

cell therapy for cardiac repair

immune attack and immunogenicity

retrovirus

OCTGT StructureOCTGT Structure

Division of Cellular and Gene TherapiesRaj 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 BranchKeith Wonnacott, Ph.D., Chief

Gene Therapies BranchDaniel Takefman, Ph.D., Chief

Gene Transfer and Immunogenicity BranchEda Bloom, Ph.D., Chief

*Acting

Cellular and Tissue Therapy Branch

Steven Bauer, Ph.D., Chief*

Products Regulated Products Regulated

by OCTGT by OCTGT Cellular therapies Cellular therapies Gene therapiesGene therapies Tumor vaccines and Tumor vaccines and

immunotherapyimmunotherapy Tissue and tissue-based productsTissue and tissue-based products Xenotransplantation productsXenotransplantation products Combination products Combination products Devices used with cells/tissueDevices used with cells/tissue

OCTGT regulatory portfolio OCTGT regulatory portfolio and activitiesand 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 Additional OCTGT regulatory portfolio and activitiesportfolio 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Guidance UpdateGuidance UpdateDraft Guidance for Industry: Preparation of IDEs Draft Guidance for Industry: Preparation of IDEs

and INDs for Products Intended to Repair or and INDs for Products Intended to Repair or Replace Knee Cartilage 7/6/07Replace Knee Cartilage 7/6/07

Guidance for Industry: Clinical Trial Endpoints for Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics the Approval of Cancer Drugs and Biologics 5/15/075/15/07

Guidance for Industry: Eligibility Determinations Guidance for Industry: Eligibility Determinations for Donors of Human Cells, Tissues, and Cellular for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products 2/27/07and Tissue-Based Products 2/27/07

Draft Guidance for Industry: Minimally Draft Guidance for Industry: Minimally Manipulated, Unrelated, Allogeneic Manipulated, Unrelated, Allogeneic Placental/Umbilical Cord Blood Intended for Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution in Patients with Hematopoietic Reconstitution in Patients with Hematological Malignancies 1/16/07Hematological Malignancies 1/16/07

Roles and work of researcher-Roles and work of researcher-reviewersreviewers

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 investigatorsContributions 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 curveApproach to research: Stay ahead of the curveas products and technologies evolveas 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 OCTGTResearch 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 Current OCTGT Research AreasAreas

VirologyVirologyRetroviruses, adeno, herpes, filoRetroviruses, adeno, herpes, filo

ImmunologyImmunologyAnti-viral immunity, immunobiology of cell therapy Anti-viral immunity, immunobiology of cell therapy and xenotransplantationand xenotransplantation

Cell biologyCell biologyControl of differentiation in animal models, Control of differentiation in animal models, stem cell biologystem cell biology

Cancer biologyCancer biologyMolecular biomarkers, animal modelsMolecular biomarkers, animal models

BiotechnologyBiotechnology Genomics, flow cytometry, proteomicsGenomics, flow cytometry, proteomics

Reference MaterialsReference Materials

Retrovirus reference material

Adenovirus reference material

RNA spike-in controls

Fluorescent standard solution

Fluorescent microbead standard

...for reviewing ...for reviewing OCTGT/DCGT/GTIBOCTGT/DCGT/GTIBresearch programsresearch programs

and providing input. and providing input.

Thank you