Process chromatography forms the core of purification of biotherapeutics. The unparalleled
selectivity that it offers over other alternatives combined with the considerable robustness and scalability
make it the unit operation of choice in downstream processing. It is typical to have three to five chromatography
steps in a purification process for a biotherapeutic. Generally, these steps offer different modes
of separation such as ion-exchange, reversed phase, size exclusion, and hydrophobic interaction. In the
past decade, multimodal chromatography has emerged as an alternative to the traditional modes. It involves
use of more than one mode of separation and typically combines ion-exchange and hydrophobic
interactions to achieve selectivity and sensitivity. Over the last decade, numerous authors have demonstrated
the significant potential that multimode chromatography offers as a protein purification tool. This
review aims to present key recent developments that have occurred on this topic together with a perspective
on future applications of multimodal chromatography.
Keywords: Multimodal chromatography/mixed-mode chromatography, MMC, mAb, Fab, antibody fragments, Biopharmaceuticals,
therapeutic proteins, host cell proteins, product related impurities, process related impurities.
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