Antibody Aggregate Removal by Multimodal Chromatography

The growing demand for therapeutic monoclonal antibodies (mAbs) has heightened the need for efficient and scalable purification strategies. A major challenge in downstream processing is the removal of antibody aggregates, which can compromise drug safety, efficacy, and regulatory compliance. This review explores the use of multimodal chromatography for aggregate separation, providing an in-depth analysis of commercially available resins and emerging adsorbent prototypes. It also examines the mechanisms of aggregate formation during bioprocessing. A comparative evaluation of conventional single-mode chromatography techniques-affinity, ion exchange, and hydrophobic interaction-is presented alongside multimodal chromatography, which integrates ion-exchange, hydrophobic, and other non-covalent interactions for enhanced aggregate clearance and process flexibility. The review primarily assesses commercial multimodal resins in terms of aggregate removal efficiency, binding capacity, and scalability. Additionally, advancements in prototype resins and multimodal membranes are discussed. Finally, the advantages, limitations, and future directions of multimodal chromatography in mAb aggregate removal are outlined. As purification demands continue to evolve, multimodal chromatography is poised to play an increasingly critical role in achieving the high purity standards required for therapeutic antibodies.