ISLET TRANSPLANTATION: FOCUS ON MANUFACTURING

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ISLET TRANSPLANTATIONFOCUS ON MANUFACTURING
Michael Millis, M.D.

• UNIVERSITY OF CHICAGO
• AND
• cGMP, Co.

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GOAL

• Develop a Islet Transplant Program that would
  withstand the anticipated regulatory requirements
• Practical for an academic institutions financial
  constraints

cGMP, Co
University of Chicago
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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
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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
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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
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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
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Temperature Controlled COBE 2991 Chilled by
Refrigerant Unit that also chills other equipment
cGMP, Co
University of Chicago
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Temperature of bath and product determines depth
of immersion
cGMP, Co
University of Chicago
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Bag being placed in heating device made for the
bag
cGMP, Co
University of Chicago
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Bag being placed in cooling device made for the
bag
cGMP, Co
University of Chicago
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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
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Acknowledgments

• Jonathan Lakey
• 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

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Additional Information
cGMP, Co. Phil Lasarsky 312 543-5523
University of Chicago Michael Millis, M.D. 773
702 6319