Rapid preparative separation of monoclonal antibody charge variants using laterally-fed membrane chromatography

Sadavarte, Rahul; Madadkar, Pedram; Filipe, Carlos D. M.; Ghosh, Raja

doi:10.1016/j.jchromb.2017.12.003

Cited by 19 publications

(15 citation statements)

References 48 publications

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“…In particular, modules that allow for diafiltrate to be dosed continuously along their length enable operations in diluting, critical, and concentrating regimes that may help to mitigate the limiting effects of fouling or gelation while utilizing less diafiltrate solution. Toward this aim, additive manufacturing has already begun to enable the development of innovative modules that increase separation efficiency of membrane chromatography − and single-stage diafiltration operations. , …”

Section: Resultsmentioning

confidence: 99%

Staged Diafiltration Cascades Provide Opportunities to Execute Highly Selective Separations

Kilmartin

Ouimet

Dowling

et al. 2021

Ind. Eng. Chem. Res.

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Improved solute selectivity, an issue commonly approached through the development of advanced membrane materials, can be achieved through staged diafiltration processes. A mathematical model that describes the solute concentration profile within a single diafiltration module is developed and experimentally validated. For this module, where the diafiltrate is introduced uniformly over its length, a critical diafiltrate flux that results in the retentate concentration remaining constant during operations is identified. The model is then extended to examine two configurations of multistage diafiltration cascades: stripping sections and rectifying sections. The two configurations differ based on the connectivity between stages. Namely, stripping sections connect multiple modules by utilizing the retentate from one stage as the feed to the subsequent stage while the permeate is repurposed as the diafiltrate. In contrast, rectifying sections utilize the permeate from one stage as the feed to the subsequent stage and the retentate becomes the diafiltrate. For cascades that operate with a constant diafiltrate to feed flow ratio for all stages, the analysis demonstrates that stripping sections can reduce the diafiltrate consumed when separating low molar mass impurities from larger, impermeable molecules. On the other hand, cascades in a rectifying section configuration can improve the separation of two solutes with finite sieving coefficients between 0 and 1. Finally, asymmetric cascades, i.e., systems in which each stage has a unique diafiltrate to feed flow ratio, are shown to be capable of improving the recovery and purity of solutes in effluent streams relative to systems that operate at constant a diafiltrate to feed ratio. As a whole, the study highlights that the continued advancement of membrane separations will rely equally on thoughtful module and process design as well as the development of new materials.

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Section: Resultsmentioning

confidence: 99%

Staged Diafiltration Cascades Provide Opportunities to Execute Highly Selective Separations

Kilmartin

Ouimet

Dowling

et al. 2021

Ind. Eng. Chem. Res.

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“…The three peaks obtained in each case (from left to right) were respectively the acidic variants peak, the main (or neutral) fraction peak, and the basic variants peak. The same monoclonal antibody (i.e., hIgG1-CD4) sample had been previously studied for the development of an analytical separation technique based on cation exchange membranes, and the presence of the acidic, neutral and basic variants in this had been clearly demonstrated [29]. Shallow gradients (i.e., 250 and 350 mL) were required to resolve the charge gradients since the physicochemical differences between them was very subtle [29].…”

Section: Resultsmentioning

confidence: 99%

“…LFMC devices outperform equivalent commercial radial-flow devices in bind-and-elute separations [23]. Their use for challenging high-resolution applications such as the purification of mono-PEGylated proteins [26], the separation of monoclonal antibody aggregates [28], and the separation of charge variants [29] has been reported. This ability to combine high-resolution with high-productivity was the main motivation for the current study, which involves a head-to-head comparison of an LFMC device with an equivalent commercial packed resin column (i.e., having similar volume and ligand chemistry).…”

Section: Introductionmentioning

confidence: 99%

Performance Comparison of a Laterally-Fed Membrane Chromatography (LFMC) Device with a Commercial Resin Packed Column

2019

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The use of conventional membrane adsorbers such as radial flow devices is largely restricted to flow-through applications, such as virus and endotoxin removal, as they fail to give acceptable resolution in bind-and-elute separations. Laterally-fed membrane chromatography or LFMC devices have been specifically developed to combine high-speed with high-resolution. In this study, an LFMC device containing a stack of strong cation exchange membranes was compared with an equivalent resin packed column. Preliminary characterization experiments showed that the LFMC device had a significantly greater number of theoretical plates per metre than the column. These devices were used to separate a ternary model protein mixture consisting of ovalbumin, conalbumin and lysozyme. The resolution obtained with the LFMC device was better than that obtained with the column. For instance, the LFMC device could resolve lysozyme dimer from lysozyme monomer, which was not possible using the column. In addition, the LFMC device could be operated at lower pressure and at significantly higher flow rates. The devices were then compared based on an application case study, i.e., preparative separation of monoclonal antibody charge variants. The LFMC device gave significantly better separation of these variants than the column.

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“…[ 80 ] This device has been successfully used for lab‐scale purification of mAb aggregates and charge variants. [ 81,82 ]…”

Section: Advances In Membrane Technology For Downstream Applicationsmentioning

confidence: 99%

Intensified Downstream Processing of Monoclonal Antibodies Using Membrane Technology

Nadar

Shooter

Somasundaram

et al. 2020

Biotechnology Journal

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The need to intensify downstream processing of monoclonal antibodies to complement the advances in upstream productivity has led to increased attention toward implementing membrane technologies. With the industry moving toward continuous operations and single use processes, membrane technologies show promise in fulfilling the industry needs due to their operational flexibility and ease of implementation. Recently, the applicability of membrane‐based unit operations in integrating the downstream process has been explored. In this article, the major developments in the application of membrane‐based technologies in the bioprocessing of monoclonal antibodies are reviewed. The recent progress toward developing intensified end‐to‐end bioprocesses and the critical role membrane technology will play in achieving this goal are focused upon.

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Rapid preparative separation of monoclonal antibody charge variants using laterally-fed membrane chromatography

Cited by 19 publications

References 48 publications

Staged Diafiltration Cascades Provide Opportunities to Execute Highly Selective Separations

Staged Diafiltration Cascades Provide Opportunities to Execute Highly Selective Separations

Performance Comparison of a Laterally-Fed Membrane Chromatography (LFMC) Device with a Commercial Resin Packed Column

Intensified Downstream Processing of Monoclonal Antibodies Using Membrane Technology

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