Abstract
Current good manufacturing practice (cGMP) islet processing facilities provide an ultraclean environment for the safe production of clinical grade islets for transplantation into immunosuppressed diabetic recipients. The objective of this study was to monitor the rate of microbial contamination in islet products after implementation of good manufacturing practice conditions. Fluid samples for microbial contamination were collected at the following steps: from the pancreas transport solution upon arrival of the organ (n = 157), after surface decontamination of the pancreas with antiseptic agents (n = 89), from islet supernatant at the end of the isolation (n = 104), and from islet supernatant as a final transplantable product after culture (n = 53). Bacterial, fungal, and mycoplasma cultures were conducted for 2, 2, and 3 weeks, respectively. Microbial contamination was detected in 31% of transport solution. The contamination was not associated with the presence of the duodenum during the preservation, cold ischemia time, or procurement team (local vs. distant). Surface decontamination of the pancreas resulted in clearance of 92% of the microbial contamination. Six preparations at the end of the isolation revealed microbial growth. All were de novo contamination during the processing. Fifty-three preparations that met our release criteria in terms of product sterility were transplanted into type 1 diabetic patients. In two instances, positive culture of the islet preparation was reported after transplantation had occurred. No patient showed any clinical findings suggestive of infection or any radiological abnormalities suggestive of abscess; a single dose of antibiotic coverage was given routinely to recipients prior to islet infusion. Although transport solution carries a high risk of microbial contamination, most contaminants become undetectable during islet processing. Microbial contamination in final products is rare, but de novo contamination still occurs during processing even under cGMP conditions.