Mechanistic Insights into Aggregation Form Elimination of Cation Exchange Membrane Chromatography
Year: 2026
Type: article
Abstract: In the field of monoclonal antibody (mAb) therapeutics, protein aggregates can significantly impact drug safety and efficacy. In standard industrial production, downstream purification processes often rely on cation-exchange chromatography (CEX) as a robust method for removing aggregates with a binding–elution mode using resin. However, this conventional approach can paradoxically trigger aggregate formation, which creates a critical bottleneck in production for certain molecules. In this study, experimental comparison revealed that switching to cation-exchange membrane chromatography effectively avoided the net HMW increase observed with the resin-based process. We hypothesize that mass transfer in conventional resins relies on diffusion, which leads to a non-uniform distribution of the sample within the column. This heterogeneity can cause localized regions of extremely high concentrations, thereby inducing aggregation for concentration-sensitive molecules. Most importantly, it suggests membrane chromatography as a promising solution for purifying concentration-sensitive proteins, avoiding the net HMW increase even under high-concentration processing conditions. It should be noted that this study was performed with a single concentration-sensitive IgG1 molecule, and the proposed mechanism remains a working hypothesis; applicability to molecules with different pI values or binding behaviors requires further evaluation.
Source: Membranes
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,654
OpenAlex ID: W7225756816
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