ATF for cell culture harvest clarification: mechanistic modelling and comparison with TFF

Abstract

AbstractBACKGROUNDExtracellular expression of proteins in mammalian cell culture systems requires clarification in order to separate the cell mass from soluble expressed protein. This task is typically accomplished by membrane based separations. This paper explores the use of alternating tangential flow (ATF) filtration for clarification.RESULTSThe superiority of ATF over the conventional tangential flow filtration (TFF) has been demonstrated with respect to the required sizing of the filter and both processes have been modeled. Modeling of TFF is based on assumptions of constant conditions of pressure, concentration of foulant, or flux. Modeling of ATF involved simultaneous variations in all three parameters and hence the traditional models that describe fouling of membranes under constant pressure filtration were appropriately modified to incorporate these variations. The resulting models are amenable to ‘exponent analysis’ and allow identification of the mechanism of ATF fouling among pore blocking, intermediate pore blocking, pore constriction, and cake formation. Complete pore blocking has been identified as the dominant mechanism for the system at hand involving clarification of mammalian cell culture harvests using ATF as well as TFF.CONCLUSIONSATF has been implemented and successfully demonstrated to be superior to TFF for mammalian cell culture clarification. The mechanism of fouling with ATF as well as TFF has been identified successfully. The modeling approach proposed here can be applied to a variety of industrial systems to determine the mode of fouling and to mitigate it. Also, sizing predictions based on mechanistic modeling can be useful for process optimization. © 2016 Society of Chemical Industry