1. 1 FDA Regulation of Cell Therapy Celia M.Witten, Ph.D., M.D. Director, Office of Cellular, Tissue, and Gene Therapies Fourth Annual Translational Stem Cell Research Conference October 13, 2009 New York, New York

2. 2 Organization CBER (Center for Biologics Evaluation and Research): vaccines, blood and blood products, human tissue/tissue products for transplantation, cells, gene therapy Office of Cellular, Tissue, and Gene Therapies Office of Vaccines Research and Review Office of Blood Research and Review CDER (Center for Drug Evaluation and Research): drugs, some biological products CDRH (Center for Devices and Radiological Health): devices for treatment, implants, diagnostic devices CVM CFSAN NCTR

3. 3 OCTGT Products Cellular therapies Tumor vaccines and immunotherapy Gene therapies Tissue and tissue based products Xenotransplantation products Combination products Devices used for cells/tissues Donor screening tests (for use with cadaveric blood samples)

4. 4 Cells: Examples of Indications/Sources Pancreatic islets for diabetes Stem and skeletal muscle progenitor cells for ischemic cardiac Hematopoietic reconstitution in treatment of malignancies Stem cells for metabolic storage diseases Stem cells for CNS indications (Parkinson’s disease) Expanded autologous cartilage for joint repair

5. 5 Regulatory Requirements for Initiating Clinical Trials Individual subject safety must be balanced against the potential public health benefits of new therapies Risk assessment requires sufficiently detailed information regarding: Product characterization and safety testing Preclinical data supporting safety Eligibility criteria Product administration procedure Clinical safety monitoring

6. 6 Common Issues that Delay Initiation of Clinical Trials Product to be used in the trial different from that used in preclinical studies Insufficient preclinical data to support safety of product administration to humans No information about compatibility of product and delivery device Inadequate plan for monitoring of subjects after product administration

7. 7 Outreach/Meetings/Policy Development

8. 8 FDA and Meetings Product specific confidential inquiries Scientific meetings Advisory Committee Discussions Workshops Liaison Meetings

9. 9 Recent Meetings/Workshops Sponsored or co-sponsored by FDA on scientific/regulatory topics: FDA/NIAID Workshop: Animal Models for the Treatment of Acute Radiation Syndrome — September 27, 2008 FDA/NIH/CIBMTR/ASBMT Workshop: Clinical Trials Endpoints for Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation — March 13, 2009 FDA/NCI Workshop: Therapeutic Cancer Vaccines Considerations for Early Phase Clinical Trials Based on Lessons Learned from Phase III — October 27, 2009 NIH/JDRF/FDA Workshop: Next Generation Beta-Cell Transplantation — November 9, 2009

10. 10 Recent Advisory Committee Meetings April 10-11 2008: Cellular Therapies Derived from Human Embryonic Stem Cells Scientific Considerations for Pre-Clinical Safety Testing Response to September 2005 Review of OCTGT Research Program FDA Somatic Cell Therapy Letter Update: OCTGT Guidance Development Program May 14-15 2009: The potential for Chlamydia trachomatis and Neisseria gonorrhea transmission by certain human cells, tissues, and cellular and tissue- based products (HCT/Ps) Animal models for porcine xenotransplantation products intended to treat Type 1 diabetes or acute liver failure Clinical issues related to the FDA draft guidance “Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage.” October 9 2009: Isolagen Therapy for moderate to severe nasolabial fold wrinkles

11. 11 Safety of Cell Therapies Derived from Human Embryonic Stem Cells April 10, 2008 Safety Concerns Product Characterization Trial Design Contributions from Advisory Committee Meetings Reviewer Experience/Interactions with Stakeholders

12. 12 2009 Guidance Documents Draft Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines 9/2009 Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products 9/2009 Draft Guidance for Industry: Somatic Cell Therapy for Cardiac Disease 3/2009 Draft Guidance for Industry: Use of Serological Tests to Reduce the Risk of Transmission of Trypanosoma cruzi Infection in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based Products 3/2009 Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) 1/2009

13. 13 Outreach/Collaborations Government organizations MATES NINDS NCI CDC NIST NHLBI Liaison meetings ISCT AATB Standards organizations ASTM AAMI ISO Research collaborations NCTR NIST NIH CDC Academic Institutions International activities WHO ICH EU

14. 14 Contact Information Celia Witten, PH.D., M.D. Office Director, OCTGT CBER/FDA 1401 Rockville Pike (HFM 70) Rockville, MD 20852-1448 witten@cber.fda.gov 301-827-5102