1. ISLET TRANSPLANTATION: FOCUS ON MANUFACTURING
Michael Millis, M.D.
UNIVERSITY OF CHICAGO
AND
cGMP, Co.

2. GOAL
Develop a Islet Transplant Program that would withstand the anticipated regulatory requirements
Practical for an academic institution’s financial constraints
cGMP, Co
University of Chicago

3. cGMP, Co Procedure that encompasses cGMP for the manufacture of
biologics
BLA ready
Reimbursable
Standard Laboratory Practice
2000 Reminder letter that FDA
regulates Islet Transplantation
3/02 Guidance regarding validation
of processing human tissues for
transplantation
cGMP, Co
University of Chicago

4. Principles for Biologic Manufacturing
Control and Validation of
Facility
Process
Goal: Make cellular (Islet) isolation conform to the Principles of Biologic Manufacturing
cGMP, Co
University of Chicago

5. Facility
Early planning matching existing institutional assets with anticipated regulatory compliance- form a good plan
Define robust process that when modified does not effect integrity of facility (validated)
Early planning to control costs
cGMP, Co
University of Chicago

6. Process
Control the critical process environment to assure product safety and repeatability
Temperature
Bio-burden
Cross-contamination
Eliminate all equipment that cannot be validated to assure absence of contamination/cross contamination
Eliminate all components that require the use of undesirable substrates
Early training of staff to assure aseptic transfer of product (SOPs, training, QA/QC)
cGMP, Co
University of Chicago

7. Temperature Controlled COBE 2991
Chilled by Refrigerant Unit that also chills other equipment
cGMP, Co
University of Chicago

8. Temperature of bath and product determines depth of immersion
cGMP, Co
University of Chicago

9. Bag being placed in heating device made for the bag
cGMP, Co
University of Chicago

10. Bag being placed in cooling device made for the bag
cGMP, Co
University of Chicago

11. Summary
Islet Isolation can be performed under conditions that adhere to BLA requirements
It requires expertise in pharmaceutical standards for laboratory and process development
cGMP, Co
University of Chicago

12. Acknowledgments Jonathan Lakey University of Chicago Camillo Ricordi
Benhard Hering
James Shapiro
State of Illinois
Tom Cross
JDRF
University of Chicago
Diane Ostrega
Marc Garfinkle
Technicians
cGMP, Co.
Phil Lasarsky
John Jarosz
Gambro/COBE

13. Additional Information
University of Chicago
Michael Millis, M.D.
– 6319
cGMP, Co.
Phil Lasarsky