Abstract
The zonal rate model (ZRM) has previously been applied for analyzing the performance of axial flow membrane chromatography capsules by independently determining the impacts of flow and binding related non-idealities on measured breakthrough curves. In the present study, the ZRM is extended to radial flow configurations, which are commonly used at larger scales. The axial flow XT5 capsule and the radial flow XT140 capsule from Pall are rigorously analyzed under binding and non-binding conditions with bovine serum albumin (BSA) as test molecule. The binding data of this molecule is much better reproduced by the spreading model, which hypothesizes different binding orientations, than by the well-known Langmuir model. Moreover, a revised cleaning protocol with NaCl instead of NaOH and minimizing the storage time has been identified as most critical for quantitatively reproducing the measured breakthrough curves. The internal geometry of both capsules is visualized by magnetic resonance imaging (MRI). The flow in the external hold-up volumes of the XT140 capsule was found to be more homogeneous as in the previously studied XT5 capsule. An attempt for model-based scale-up was apparently impeded by irregular pleat structures in the used XT140 capsule, which might lead to local variations in the linear velocity through the membrane stack. However, the presented approach is universal and can be applied to different capsules. The ZRM is shown to potentially help save valuable material and time, as the experiments required for model calibration are much cheaper than the predicted large-scale experiment at binding conditions. Biotechnol. Bioeng. 2013; 110: 1129–1141. © 2012 Wiley Periodicals, Inc.
Highlights
Packed bed chromatography is one of the most widely employed purification steps in biopharmaceutical industry
Breakthrough experiments performed under non-binding conditions provide insights into solute dispersion within the studied membrane chromatography capsules
The zonal rate model (ZRM) has previously been applied for analyzing the performance of axial flow membrane chromatography capsules by independently determining the impacts of flow and binding related non-idealities on measured breakthrough curves
Summary
Packed bed chromatography is one of the most widely employed purification steps in biopharmaceutical industry. High resolution makes it an indispensable unit operation in the recovery of therapeutic proteins and recombinant drugs where purity is of utmost importance. Membrane chromatography is a very attractive alternative due to many beneficial features (Endres et al, 2003; Ghosh, 2001; Klein, 2000; Przybycien and Pujar, 2004; Saxena et al, 2009; Teeters et al, 2003; Vogel et al, 2012), such as the potential of working at higher flow rates while maintaining binding capacities at comparable levels to packed bed chromatography. Membrane chromatography capsules are often disposable, which can offer additional advantages over packed bed chromatography, as cleaning steps are not required
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