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. Discussion: 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.