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Continuous bind‐and‐elute protein A capture chromatography: Optimization under process scale column constraints and comparison to batch operation
Author(s) -
Kaltenbrunner Oliver,
Diaz Luis,
Hu Xiaochun,
Shearer Michael
Publication year - 2016
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2291
Subject(s) - residence time (fluid dynamics) , simulated moving bed , pressure drop , batch processing , downstream processing , process engineering , packed bed , column (typography) , volumetric flow rate , continuous flow , chromatography , cascade , elution , productivity , drop (telecommunication) , flow (mathematics) , environmental science , computer science , chemistry , adsorption , mathematics , engineering , mechanics , physics , geometry , geotechnical engineering , organic chemistry , biochemical engineering , economics , macroeconomics , programming language , telecommunications , frame (networking)
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