Protein a chromatography at high titers

Natarajan, Venkatesh; Zydney, Andrew L.

doi:10.1002/bit.24902

Cited by 37 publications

(30 citation statements)

References 16 publications

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“…The entire data set was fit to the Langmuir isotherm resulting in a maximum binding capacity, q m = 7.20 ± 0.15 mg/mL, and equilibrium dissociation constant, K d = 0.11 ± 0.02 mg/mL. The IgG binding capacity with CIM discs is significantly lower than those reported for various commercial Protein A resins which vary according to the support used and range from 25 to 70 mg/mL [35][36][37]. However, the CIM discs may still provide overall process improvement through increased throughput, as is shown later.…”

Section: Equilibrium Binding Isothermmentioning

confidence: 98%

Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium

Herigstad

Dimartino

Boi

et al. 2015

Journal of Chromatography A

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Section: Equilibrium Binding Isothermmentioning

confidence: 98%

Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium

Herigstad

Dimartino

Boi

et al. 2015

Journal of Chromatography A

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“…However, with the significant increase in cell culture titers (∼5–10 g/L) in the last couple of decades, the inherent drawbacks associated with the lower capacity and high cost of Protein A resins become more apparent. With typical loading capacity of most Protein A resins being <40 mg/mL, many large scale processes are facing a bottleneck with purifying high titer feed streams . Increasing column size to accommodate higher titers leads to exorbitant increases in economic costs .…”

Section: Introductionmentioning

confidence: 99%

Maximizing binding capacity for protein A chromatography

Ghose

Zhang

Conley

et al. 2014

Biotechnology Progress

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Advances in cell culture expression levels in the last two decades have resulted in monoclonal antibody titers of ≥10 g/L to be purified downstream. A high capacity capture step is crucial to prevent purification from being the bottleneck in the manufacturing process. Despite its high cost and other disadvantages, Protein A chromatography still remains the optimal choice for antibody capture due to the excellent selectivity provided by this step. A dual flow loading strategy was used in conjunction with a new generation high capacity Protein A resin to maximize binding capacity without significantly increasing processing time. Optimum conditions were established using a simple empirical Design of Experiment (DOE) based model and verified with a wide panel of antibodies. Dynamic binding capacities of >65 g/L could be achieved under these new conditions, significantly higher by more than one and half times the values that have been typically achieved with Protein A in the past. Furthermore, comparable process performance and product quality was demonstrated for the Protein A step at the increased loading.

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“…Figure shows examples of predicted BTCs for a range of load concentrations ( C 0 ) and a range of residence times ( t R ). The predicted curves behave as described by Natarajan and Zydney; higher load concentration leads to earlier breakthrough at low residence time and later breakthrough at high residence time.…”

Section: Resultsmentioning

confidence: 99%

Continuous bind‐and‐elute protein A capture chromatography: Optimization under process scale column constraints and comparison to batch operation

Kaltenbrunner

Díaz

et al. 2016

Biotechnology Progress

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Recently, continuous downstream processing has become a topic of discussion and analysis at conferences while no industrial applications of continuous downstream processing for biopharmaceutical manufacturing have been reported. There is significant potential to increase the productivity of a Protein A capture step by converting the operation to simulated moving bed (SMB) mode. In this mode, shorter columns are operated at higher process flow and corresponding short residence times. The ability to significantly shorten the product residence time during loading without appreciable capacity loss can dramatically increase productivity of the capture step and consequently reduce the amount of Protein A resin required in the process. Previous studies have not considered the physical limitations of how short columns can be packed and the flow rate limitations due to pressure drop of stacked columns. In this study, we are evaluating the process behavior of a continuous Protein A capture column cycling operation under the known pressure drop constraints of a compressible media. The results are compared to the same resin operated under traditional batch operating conditions. We analyze the optimum system design point for a range of feed concentrations, bed heights, and load residence times and determine achievable productivity for any feed concentration and any column bed height. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:938-948, 2016.

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Protein a chromatography at high titers

Cited by 37 publications

References 16 publications

Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium

Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium

Maximizing binding capacity for protein A chromatography

Continuous bind‐and‐elute protein A capture chromatography: Optimization under process scale column constraints and comparison to batch operation

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