Deborah Hursh, Ph.D. Office of Cellular, Tissue, and Gene Therapies
Cellular Tissue and Gene Therapies Research Site Visit Celia M.Witten, Ph.D., M.D. Director, Office...
Transcript of Cellular Tissue and Gene Therapies Research Site Visit Celia M.Witten, Ph.D., M.D. Director, Office...
![Page 1: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/1.jpg)
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
![Page 2: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/2.jpg)
Outline
• Office Overview
• Research Vision
• Products Regulated
• Organizational Structure
• Regulatory challenges and opportunities
• Research program areas
![Page 3: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/3.jpg)
OCTGT Mission
• Facilitate development, approval, and access to safe and effective medical products
![Page 4: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/4.jpg)
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
![Page 5: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/5.jpg)
Patients
Research Community
FDA
Public
Sponsors
Practitioners/Societies
Payors
Medical Institutions
![Page 6: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/6.jpg)
OCTGT Research Vision
• Facilitate critical path development
• Identify cross-cutting/or applied science/biomedical technology issues
• Resolve scientific questions critical to regulation
![Page 7: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/7.jpg)
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
![Page 8: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/8.jpg)
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
![Page 9: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/9.jpg)
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
![Page 10: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/10.jpg)
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
![Page 11: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/11.jpg)
Product Manufacture and Characterization
• Cell or tissue source
• Processing and manufacturing
• Product identity and purity
• Measuring product potency
• Manufacturing change/comparability study
• Stability data
![Page 12: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/12.jpg)
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
![Page 13: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/13.jpg)
Product Safety, Continued
• Dosing?
• Toxicity?
• Immunogenicity?
• Proof of concept?
• Product administration?
• Safety monitoring?
![Page 14: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/14.jpg)
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
![Page 15: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/15.jpg)
Clinical Study Design
• Method of product administration
• Goal of treatment
• Timing of evaluations/study duration
• Standard of care
• Concomitant treatment
![Page 16: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/16.jpg)
Clinical Study Design: Therapeutic Tumor Vaccines
• Timing of response
• Immunological response in subpopulation
• Objective of treatment: halt disease progression versus tumor regression
![Page 17: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/17.jpg)
Regulation of Human Tissue
• Registration and Listing of Establishments
• Donor Eligibility
• Good Tissue Practices
• Final Rules published
• All effective May 25, 2005
![Page 18: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/18.jpg)
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
![Page 19: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/19.jpg)
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
![Page 20: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/20.jpg)
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
![Page 21: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/21.jpg)
Outreach Activities
• ISCT Liaison meeting June 2005
• ISCT Symposium September 2005
• Cancer Vaccine Consortium Workshop November 2005
![Page 22: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/22.jpg)
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
![Page 23: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/23.jpg)
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
![Page 24: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/24.jpg)
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
![Page 25: 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,](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d925503460f94a78ffc/html5/thumbnails/25.jpg)
Thank You