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RESEARCH ARTICLE
Cation exchange membrane chromatography: An efficient alternative to multi-column for avoiding the impact of loading density variation on performance
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1
Downstream Process Development (DSPD), WuXi Biologics, Shanghai 200131,
China
JBM, e99010087 https://doi.org/10.14440/jbm.0213
Submitted: 22 July 2025 | Revised: 26 September 2025 | Accepted: 9 October 2025 | Published: 27 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Background: Resin-based cation exchange (CEX) column chromatography is widely used for charge variant separation/reduction. However, in a CEX process where a wash step is introduced to reduce weakly bound acidic charge variants, its performance is greatly affected by the loading density, resulting in poor robustness. We previously demonstrated that multi-column chromatography could resovle this problem, with the key strategy involving converting 3–4 large cycles into a greater number of small cycles. Recently, membrane chromatography has emerged as a promising alternative to column chromatography. CEX membrane, which can be operated under high flow rate, naturally supports the conversion of a large cycle into numerous small cycles. Objective: This study aimed to demonstrate that CEX membrane chromatography offers a superior option for addressing the low robustness in the chromatography’s wash step. Methods: CEX membrane chromatography was applied to reduce acidic charge variants, and its effectiveness was evaluated using capillary isoelectric focusing analysis of the purified samples. Results: Under appropriate conditions, CEX membrane chromatography consistently lowered acidic charge variants to the required level. Conclusion: Compared to the multi-column approach, CEX membrane chromatography allows for a more straightforward implementation, has higher productivity, and achieves greater cost efficiency. Therefore, it serves as a better alternative to address the low robustness issue.
Keywords
Acidic charge variant
Bind–elute mode
Cation exchange membrane
Robustness
Wash
Weakly bound byproduct
Funding
None.
Conflict of interest
The authors are employees of WuXi Biologics (Shanghai) Co., Ltd. The authors declare that this affiliation did not influence the study design, data interpretation, or manuscript preparation. No other conflicts of interest, financial or otherwise, are declared.
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