Cellular Tissue and Gene Therapies

Research Site Visit

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

Director, Office of Cellular, Tissue, and Gene Therapies

September 29, 2005

Outline

• Office Overview

• Research Vision

• Products Regulated

• Organizational Structure

• Regulatory challenges and opportunities

• Research program areas

OCTGT Mission

• Facilitate development, approval, and access to safe and effective medical products

Science in Research and Review: Critical Path Initiative

• Bring scientific advances to medical product development process (simulation models, validated biomarkers, new clinical trial designs)

• Stimulate development of applicable research programs in critical path scientific areas, aim to develop techniques that address challenges encountered during product development

• Regulatory guidance/practice and standards to reflect best available science, integrate FDA involvement

Patients

Research Community

FDA

Public

Sponsors

Practitioners/Societies

Payors

Medical Institutions

OCTGT Research Vision

• Facilitate critical path development

• Identify cross-cutting/or applied science/biomedical technology issues

• Resolve scientific questions critical to regulation

Setting Priorities

• Resources are limited

• Are we investing our energies in the most important activities?

• Are resources distributed in accordance with our priorities?

• Challenge: our scope is large

OCTGT Regulation

• Cellular therapies • Tumor vaccines• Gene therapies• Tissue and tissue based products• Xenotransplantation products• Combination products • Devices used for cells/tissues• Anti-idiotype antibodies

Office of Cellular, Tissue, and Gene TherapiesCelia M.Witten, Ph.D, M.D. Office Director

Stephen Hilbert, Ph.D., M.D. Acting Deputy DirectorSuzanne Epstein, Ph.D., Associate Director for Research

Division of Cellular and Gene TherapiesRaj Puri, Ph.D., M.D., Director

Stephanie Simek, Ph.D., Deputy Director

Division of Human Tissue ProductsRuth Solomon, M.D., Director

Division of Clinical Evaluation and Pharmacology/ToxicologyRecruiting

Regulatory Challenges/Scientific Opportunities

• How is the product made and characterized?

• What level of safety assurance is needed for beginning clinical trials?

• Clinical study design

Product Manufacture and Characterization

• Cell or tissue source

• Processing and manufacturing

• Product identity and purity

• Measuring product potency

• Manufacturing change/comparability study

• Stability data

Product Safety

• Donor testing and screening

• Microbiological testing of the final product

• Safety testing on critical reagents

• Replication competence

• Product tracking for patient specific products

Product Safety, Continued

• Dosing?

• Toxicity?

• Immunogenicity?

• Proof of concept?

• Product administration?

• Safety monitoring?

Clinical Study Design: Early Phase

• Product development versus research

• What is the appropriate patient population? (“orphan” indications, heterogeneous patients, pediatric issues)

• How can patients be best monitored for safety

• Dose escalation plan/dose selection

Clinical Study Design

• Method of product administration

• Goal of treatment

• Timing of evaluations/study duration

• Standard of care

• Concomitant treatment

Clinical Study Design: Therapeutic Tumor Vaccines

• Timing of response

• Immunological response in subpopulation

• Objective of treatment: halt disease progression versus tumor regression

Regulation of Human Tissue

• Registration and Listing of Establishments

• Donor Eligibility

• Good Tissue Practices

• Final Rules published

• All effective May 25, 2005

Scope: 1271.1(b)

• Articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer

• “361” registration and inspection• “351” biological products subject to

licensure• “HCT/Ps regulated under FDCA”: medical

devices subject to clearance/approval

Hot Topics

• Minimal manipulation/homologous use• Devices used to make/process cells and tissues• CGTP implementation, CGTP/GMP• International harmonization • Adverse events• Donor screening/testing • Cord blood• Pancreatic islet cells• Tumor vaccines clinical study design• Potency assays• Iterative changes in product design

Outreach Activities

• Long-Term Follow-up Workshop June 2004

• ASGT Stakeholder’s Meeting April 7 and 8, 2005

• BIO Liaison Meeting July 2005

• ICH: Fall workshop on oncolytic virus

Outreach Activities

• ISCT Liaison meeting June 2005

• ISCT Symposium September 2005

• Cancer Vaccine Consortium Workshop November 2005

Guidance Documents• Draft Guidance for Industry: Gene Therapy Clinical Trials - Observin

g Participants for Delayed Adverse Events - 8/23/2005

• Draft Guidance for FDA Review Staff and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Iformation for Human Gene Therapy Investigational New Drug Applications (INDs) - 11/8/2004

• Draft Guidance for Reviewers: Instructions and Template for Chemistry, Manufacturing, and Control (CMC) Reviewers of Human Somatic Cell Therapy Investigational New Drug Applications (INDs) - 8/15/2003

• Guidance for Industry: Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors - 10/18/2000

• Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy - 3/30/1998

Tissue Regulation Websites

• http://www.fda.gov/cber/tissue/docs.htm

• Draft Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) - 5/20/2004

Research Program Areas

• Virology– Retroviruses, adeno, herpes, PERV

• Immunology– Host-vector interactions, transplant rejection

• Cell biology– Control of differentiation in animal models, stem cell

biology• Cancer biology

– Molecular biomarkers, animal models• Biotechnology

– Microarray, proteomics, flow cytometry, transgenics

Thank You