Zonal rate model for axial and radial flow membrane chromatography, part II: Model‐based scale‐up

Abstract

Membrane chromatography (MC) systems are finding increasing use in downstream processing trains for therapeutic proteins due to the unique mass-transfer characteristics they provide. As a result, there is increased need for model-based methods to scale-up MC units using data collected on a scaled-down unit. Here, a strategy is presented for MC unit scale-up using the zonal rate model (ZRM). The ZRM partitions an MC unit into virtual flow zones to account for deviations from ideal plug-flow behavior. To permit scale-up, it is first configured for the specific device geometry and flow profiles within the scaleddown unit so as to achieve decoupling of flow and binding related non-idealities. The ZRM is then configured for the preparative-scale unit, which typically utilizes markedly different flow manifolds and membrane architecture. Breakthrough is first analyzed in both units under nonbinding conditions using an inexpensive tracer to independently determine unit geometry related parameters of the ZRM. Binding related parameters are then determined from breakthrough data on the scaled-down MC capsule to minimize sample requirements. Model-based scale-up may then be performed to predict band broadening and breakthrough curves on the preparative-scale unit. Here, the approach is shown to be valid when the Pall XT140 and XT5 capsules serve as the preparative and scaled-down units, respectively. In this case, scale-up is facilitated by our finding that the distribution of linear velocities through the membrane in the XT140 capsule is independent of the feed flow rate and the type of protein transmitted. Introduction of this finding into the ZRM permits quantitative predictions of breakthrough over a range of industrially relevant operating conditions.

The use of predictive models to develop chromatography-based purification processes

“…When combined with the total (geometric) column volume and the particle solid volume, they can be used to calculate the inter-particle porosity (also known as column porosity) and the intra-particle porosity (also known as particle porosity). The latter values are needed to solve the partial differential equations of rate models that describe mass transport around the stationary phase ( Wiesel et al, 2003 ; Orellana et al, 2009 ; Ghosh et al, 2014 ) and they can be combined with isotherms to model the binding of proteins ( Brooks and Cramer 1992 ; Wang et al, 2016 ).…”

Evaluation of Continuous Membrane Chromatography Concepts with an Enhanced Process Simulation Approach

“…This aspect was already addressed by Roper et al [64] who implemented stirred tanks before and after the column, as shown in Figure 5B. A further improvement is the multi-stage approach called “zonal rate model”, first introduced by Francis et al (Figure 5C) [59,60,65,66].…”

Model-based process design of a ternary protein separation using multi-step gradient ion-exchange SMB chromatography

“…Clark et al (2007) used an acoustically actuated resonant membrane sensor to monitor the changes of surface energy and found that the changes persist long after mass loading of the protein has reached the steady state. Therefore, more sophisticated adsorption models, such as the multi-state sma (Diedrich et al, 2017) based on the spreading model (Ghosh et al, 2013(Ghosh et al, , 2014, have been proposed to describe dynamic protein-ligand interactions. Although these kinetics describe more accurately the adsorption behaviors by taking orientation changes into consideration, the strong nonlinearity of kinetics exerts tremendous difficulties in deriving analytical formulae to calculate flowrates, as it is in the triangle theory.…”