Filtrate Flux and Sieving Characteristics of Virus Filtration Membranes
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Filtrate Flux and Sieving Characteristics of Virus Filtration Membranes Andrew L. Zydney and David M. Bohonak Department of Chemical Engineering, The Pennsylvania State University University Park, PA 16802 ABSTRACT Virus filtration is increasingly used in the biopharmaceutical industry, but capacity and fouling remain problematic. Experimental studies were conducted in dead-end, stirred filtration cells with Viresolve 180 polyvinylidene fluoride membranes using the protein bovine serum albumin. Data were obtained for membranes in two different flow orientations, with the selective "skin" layer oriented on either the upstream surface or downstream relative to the fluid flow. Compaction of the substructure occurs when the skin layer is downstream, leading to a significant increase in membrane resistance. Concentration polarization in the bulk solution or membrane substructure caused a substantial increase in the protein sieving coefficient, with this effect being greatest when the flow entered through the substructure. Fouling is primarily due to the deposition of large protein aggregates. The effect of this fouling on the flux was reduced when the skin layer was oriented downstream since the substructure acted as a prefilter. These results demonstrate that the membrane morphology and orientation play a critical role in determining the overall performance of virus filtration membranes.
INTRODUCTION Over the past 30 years, viral outbreaks of hepatitis A [1-4] and hepatitis C [5-7] have been attributed to contaminated blood-related products in the United States, Africa, and Europe. To prevent viral outbreaks, the USFDA and the European Union recommend that biopharmaceutical manufacturers utilize a multi-step strategy capable of reducing virus titres by 12 orders of magnitude [8]. Ultrafiltration membranes offer an opportunity to complement other virus clearance steps by providing a robust, primarily size-based viral removal process. Virus filtration membranes must be free of defects and large macrovoids that could pentrate the skin and allow passage of viruses. Although several studies have demonstrated the viral clearance capabilities of these membranes [9], little research has focused on the underlying mechanisms controlling protein sieving and flux. The goal of this research was to develop a more complete understanding of the fundamental mechanisms governing the behavior of virus filters, including membrane compaction, concentration polarization, and membrane fouling. Special attention is directed to the effects of the membrane structure, morphology, and orientation.
EXPERIMENTAL DETAILS Experiments were conducted with the Viresolve 180 membrane (Millipore Corp., Bedford, MA). This hydrophilic polyvinylidene fluoride membrane consists of two distinct layers: a thin skin layer that provides the membrane selectivity and a substructure having micron-
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sized pores that provides structural support. Membrane sheets were cut into 25 mm disks. The membranes were used in two orientations. In the “normal
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