Day 2

1
Day 2

• Allogeneic Islet Transplantation
• Cynthia A. Rask, M.D.
• Director, Division of Clinical Evaluation and
  Pharmacology/Toxicology (DCEPT)
• FDA/CBER/OCTGT
• October 10, 2003

2
Introduction

• Brief Summary of FDAs understanding of
  discussions held on October 9, 2003
• Ensuring Quality of Source Pancreata
• Manufacturing of Islets
• Assessing the Final Product
• Islet Comparability

3
Ensuring the Quality of Source Pancreata

• Each donor pancreas has unique characteristics
  such as age of donor, size of organ, extent of
  fibrosis and autololysis, ischemia time
• But pre-defined acceptance criteria should be
  established, standardized and validated

4
Manufacturing of Islets

• FDA may allow some flexibility as long as the
  manufacturing is conducted using predefined
  criteria or algorithms within a validated
  protocol
• These predefined criteria might establish
  conditions that would allow for minor processing
  changes based on each donor organs
  characteristics

5
Assessing the Final Product

• Specific product safety and quality testing must
  be done on the final product and results must be
  available prior to administration to the patient
• Various product potency assays were discussed ---
  ideally, the results from a potency assay should
  be available prior to administration of the
  product

6
Islet Comparability

• Demonstration that changes made to the
  manufacturing process have not altered critical
  product characteristics, including
• Safety
• Identity
• Purity
• Potency
• Consistency
• Stability

7
Clinical Development of Islet Products

• Availability of steroid-free immunosuppressive
  regimens
• Improvements in islet isolation techniques
• Evaluation of risks and benefits

8
Clinical Discussions

• Current Status of Islet Cell Transplantation
  Dr. James Shapiro
  (Univ. Alberta)
• Current Processes and Procedures for Allocation
  of Donor Pancreata Dr. James Burdick (HRSA)

9
Clinical Discussions (contd)

• Ethical Considerations Dr. James
  Childress (UVa)
• Clinical Development Programs for Islet Products
  Dr. Dwaine Rieves
  (CBER/FDA)