Cellular Tissue and Gene Therapies Research Site Visit

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Cellular Tissue and Gene TherapiesResearch Site
Visit

• Celia M.Witten, Ph.D., M.D.
• Director, Office of Cellular, Tissue, and Gene
  Therapies
• September 29, 2005

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Outline

• Office Overview
• Research Vision
• Products Regulated
• Organizational Structure
• Regulatory challenges and opportunities
• Research program areas

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OCTGT Mission

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

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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

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OCTGT Research Vision

• Facilitate critical path development
• Identify cross-cutting/or applied
  science/biomedical technology issues
• Resolve scientific questions critical to
  regulation

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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

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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

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Office of Cellular, Tissue, and Gene
Therapies Celia M.Witten, Ph.D, M.D. Office
Director Stephen Hilbert, Ph.D., M.D. Acting
Deputy Director Suzanne Epstein, Ph.D., Associate
Director for Research
Division of Cellular and Gene Therapies Raj Puri,
Ph.D., M.D., Director Stephanie Simek, Ph.D.,
Deputy Director
Division of Human Tissue Products Ruth Solomon,
M.D., Director
Division of Clinical Evaluation and
Pharmacology/Toxicology Recruiting
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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

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Product Manufacture and Characterization

• Cell or tissue source
• Processing and manufacturing
• Product identity and purity
• Measuring product potency
• Manufacturing change/comparability study
• Stability data

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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

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Product Safety, Continued

• Dosing?
• Toxicity?
• Immunogenicity?
• Proof of concept?
• Product administration?
• Safety monitoring?

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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

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Clinical Study Design

• Method of product administration
• Goal of treatment
• Timing of evaluations/study duration
• Standard of care
• Concomitant treatment

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Clinical Study Design Therapeutic Tumor Vaccines

• Timing of response
• Immunological response in subpopulation
• Objective of treatment halt disease progression
  versus tumor regression

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Regulation of Human Tissue

• Registration and Listing of Establishments
• Donor Eligibility
• Good Tissue Practices
• Final Rules published
• All effective May 25, 2005

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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

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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

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Outreach Activities

• Long-Term Follow-up Workshop June 2004
• ASGT Stakeholders Meeting April 7 and 8, 2005
• BIO Liaison Meeting July 2005
• ICH Fall workshop on oncolytic virus

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Outreach Activities

• ISCT Liaison meeting June 2005
• ISCT Symposium September 2005
• Cancer Vaccine Consortium Workshop November 2005

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Guidance Documents

• Draft Guidance for Industry Gene Therapy
  Clinical Trials - Observing 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

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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

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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

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Thank You