A multicenter comparison study between the Endosafe PTS rapid-release testing system and traditional methods for detecting endotoxin in cell-therapy products.
BACKGROUND
Rapid-release testing reduces the waiting period for administration of time-sensitive cell-therapy products. Current assay systems are labor intensive and time consuming. The Endosafe portable test system (PTS) is a chromogenic Limulus amebocyte lysate (LAL) portable endotoxin detection system that provides quantitative results in approximately 15 min. To evaluate Endosafe performance with cell-therapy products, side-by-side testing of traditional LAL systems and the Endosafe system was conducted at the Production Assistance for Cellular Therapies (PACT) facilities and the National Institutes of Health's Department of Transfusion Medicine, USA.


METHODS
Charles River Laboratories provided each center with a PTS reader and two commercially prepared lyophilized reference standard endotoxin (RSE) vials. All samples tested with the Endosafe system used 0.05-5.0 endotoxin unit/mL (EU/mL) sensitivity cartridges provided by Charles River. Each vial was reconstituted with LAL water and tested in triplicate using the Endosafe and in-house LAL methods. Subsequently, each center tested the endotoxin content of standard dilutions of cell-therapy products, thus creating paired test results for each sample. Additionally, fabricated endotoxin-positive samples containing varying concentrations of endotoxin were prepared and shipped to all centers to perform blinded testing.


RESULTS
Valid paired results, based on each center's LAL method and the Endosafe system criteria, were analyzed. Endotoxin detection between paired results was equivalent in most cases.


CONCLUSIONS
The Endosafe system provided reliable results with products typically produced in cell-therapy manufacturing facilities, and would be an appropriate test on which to base the release of time-sensitive cell-therapy products.
Center for Cell and Gene Therapy (CAGT), Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030, USA. apgee@txccc.org
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Gee
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Sumstad
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Stanson
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Watson
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Proctor
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Kadidlo
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Koch
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Sprague
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Wood
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Styers
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McKenna
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Gallelli
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Griffin
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Read
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Parish
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Lindblad
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D019411:Clinical Laboratory Techniques; D004340:Drug Contamination; D004731:Endotoxins / Q000032:analysis*; D006801:Humans; D008033:Limulus Test / Q000295:instrumentation / Q000379:methods; D012015:Reference Standards; D015203:Reproducibility of Results; D013997:Time Factors
D004731:Endotoxins