A Framework for the Prediction of Scale‐Up When Using Compressible Chromatographic Packings

Abstract

Experimental data are given for the solid pressure distributions in chromatography columns of various column aspect ratios packed with four types of agarose-based resin. The loss of column wall support at large scales can result in unexpectedly high pressures caused by the compression of the matrix via drag forces exerted by fluid flow through the bed. The need for an accurate model to predict flow conditions at increasing scale is essential for the scaling-up of chromatographic processes and for avoiding bed compression during operation. Several studies have generated correlations that allow for the prediction of column pressure drops, but they either are mathematically complex, which impairs their practical use, or require a large number of experiments to be performed before they can be used. In this study an empirical correlation was developed based on a previously proposed model, which links the critical velocity of operation of a chromatographic system (microcrit), to the gravity-settled bed height (L0), the column diameter (D), the feed viscosity (micro), and the compressibility of the chromatographic media used (micro 10%). The methodology developed in this study is straightforward to use and significantly reduces the burden of preceding laboratory-scale experimentation. The approach can be used to predict the critical velocity of any chromatographic system and will be useful in the development of chromatographic operations and for column sizing.

Fiber chromatographic enabled process intensification increases monoclonal antibody product yield

“…This transport phenomenon can be observed, for example, during traditional agarose‐based protein A (proA) affinity capture chromatography in monoclonal antibody (mAb) purification (Natarajan & Zydney, 2013). ProA cross‐linked agarose beads are porous and compressible, which limits the flow rate of the mobile phase (Tran et al, 2007). Most of the surface area and ligand density are found in the bead interior and require high residence times to allow protein diffusion to maintain high binding capacity (Hahn et al, 2003).…”

“…This directly impacts the pressure applied to the resin as the mobile phase is forced through these narrow channels, increasing the pressure (Kong et al, 2018). Consequently, the traditional use of agarose beads requires low flow rates to achieve high binding capacity and to prevent crushing the bed (Tran et al, 2007). Fiber chromatography has altered these dynamics, enabling an increase in productivity using convective transport (Davis et al, 2021).…”