Optimized Continuous Multicolumn Chromatography Enables Increased Productivities and Cost Savings by Employing More Columns

Abstract

The advantages of continuous chromatography with respect to increased capacity are well established. However, the impact of different loading scenarios and total number of columns on the process economics has not been addressed. Here four different continuous multicolumn chromatography (MCC) loading scenarios are evaluated for process performance and economics in the context of a Protein A mAb capture step. To do so, a computational chromatography model is validated experimentally. The model is then used to predict process performance for each of the loading methods. A wide range of feed concentrations and residence times are considered, and the responses of operating binding capacity, specific productivity, and the number of process columns are calculated. Processes that are able to add more columns proved to be up to 65% more productive, especially at feed concentrations above 5 g L−1. An investigation of the operating costs shows that discrete column sizing and process performance metrics do not always correlate and that the most productive process is not necessarily the most cost effective. However, adding more columns for the non‐load steps at higher feed concentrations allows for overall cost savings of up to 32%.

Truly continuous low pH viral inactivation for biopharmaceutical process integration

“…The biopharmaceutical industry is following other industries in moving from discrete batch operation to integrated continuous manufacturing, especially for high demand products, such as monoclonal antibodies (MAbs; Shukla, Wolfe, Mostafa, & Norman, 2017; Walsh, 2018). The drivers for continuous processing are many‐fold; process intensification and cost savings (Baur, Angarita, Müller‐Späth, Steinebach, & Morbidelli, 2016; Hummel et al, 2018; Pagkaliwangan, Hummel, Gjoka, Bisschops, & Schofield, 2018; Pollock, Coffman, Ho, & Farid, 2017) might emerge as the most obvious ones but steady‐state operation and thus better, more reproducible quality have also been associated with continuous biomanufacturing (Karst et al, 2017; Kaufman, Wasley, & Dorner, 1988; Walther et al, 2019). While upstream processing is ahead in this transition, where chemostat and perfusion reactors are commonly employed at the manufacturing scale (Arathoon & Birch, 1986; Shukla et al, 2017; Warnock & Al‐Rubeai, 2006), downstream operations have only in recent years started this transition.…”

Validation and optimization of viral clearance in a downstream continuous chromatography setting

“…Many examples have been published to show this approach can increase resin utilization and increase productivity. This opens up the possibility to reduce the amount of resin required in a commercial bioprocess and improve manufacturing economics (Baur, Angarita, Müller‐Späth, Steinebach, & Morbidelli, ; Bisschops & Brower, ; Dutta, Tan, Napadensky, Zydney, & Shinkazh, ; Girard et al, ; Jagschies, ; Pagkaliwangan, Hummel, Gjoka, Bisschops, & Schofield, ; Warikoo et al, ; Xenopoulos, )…”

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

“…By operating many chromatography columns in a countercurrent or concurrent manner, continuous operation can be achieved, as the loading is carried out in the first column and all of the other steps (washing, elution, regeneration, and re-equilibration) in the subsequent ones (Jungbauer, 2013). Continuous annular chromatography (CAC), simulated moving bed (SMB) chromatography, countercurrent chromatography (CCC), multicolumn countercurrent solvent gradient purification chromatography (MCSGP), and countercurrent tangential (CCT) chromatography are used in the continuous mode of operation (Pagkaliwangan et al, 2018;Rathore et al, 2018;Vogg et al, 2018). Some of the commercially available continuous chromatography platforms are listed in Table 6.…”

“…In a scale-up study for purification of mAbs, it was reported that buffer savings of around 50% were achieved using a PCC strategy (Angelo et al, 2018). Four different loading scenarios with a Cadence BioSMB MCC for the Protein A mAb capture step were evaluated, and it was concluded that by adding more columns, up to 65% more productivity (at feed concentrations of above 5 g/l) could be achieved (Pagkaliwangan et al, 2018). The effect of particle size (85 vs. 50 µm) on the performance of continuous capture Protein A affinity chromatography was studied with respect to feed titers, load flow rates, and target breakthrough with single column batch, two-column CaptureSMB, and four-column PCC using a DOE approach.…”