Pathogen safety profile of a 10% IgG preparation manufactured using a depth filtration-modified process

Gamunex (R)-C is a highly purified liquid 10% IgG preparation manufactured by a process that includes caprylate precipitation and incubation, and chromatography steps. In the original process, caprylate precipitation was followed by cloth filtration to remove impurities. The highly porous cloth filter has since been replaced with a tight depth filter. The impact of this process modification on pathogen reduction and product is presented. Virus and prion reduction was determined under set-point conditions using scaled-down models of the manufacturing process, and at or outside operating limits to determine robustness. Product protein compositions before and after the process modification were compared directly using manufacturing data. Filtration through a tight depth filter substantially increased nonenveloped virus reduction, and virus reduction was maintained even when a compromised depth filter was used. In addition, prion reduction was improved by about three logs. The product IgG content, purity, and IgG subclass distribution remained comparable to the original cloth filtration process. The replacement of cloth filtration with depth filtration increased the pathogen safety margin of the manufacturing process without impacting the product composition. (C) 2012 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.