Analysis of fouling within microporous membranes in biopharmaceutical applications using latex microsphere suspensions

Abstract

A better understanding of how biological fluids foul membrane filters will allow membranes to be better designed and more appropriately chosen for the filtration of biopharmaceutical products. For this study, a model fluid has been developed to facilitate the study of membrane loading capacity and particle retention using normal flow, polymeric microporous membranes for liquid-phase sterile filtration. The model fluid approximates process fluids that have high loads of submicron particles (such as cell debris and agglomerated proteins), as found in cell culture harvests. Using this model fluid, foulants can be visualized within the membrane structure by advanced electron microscopy techniques, giving insight to where and in some cases how fouling occurs. While the model fluid was not a perfect mimic of the biological fluids to which we compared it, fouling did occur within the same region of the membrane, indicating that the model fluid could be used to understand fouling trends. By using the right model fluid, the relative performance of the membrane tested was the same as in relevant biological fluids, so that while absolute capacities could not be reproduced with the model fluids, the fouling trends that impact capacity for biological fluids could be approximated.