Pooling control in variable preparative chromatography processes.
Preparative chromatographic columns that run at high loads are highly sensitive to batch-to-batch disturbances of the process parameters, placing high demands on the strategy used for pooling of the product fractions. A new approach to pooling control is presented in a proof-of-concept study. A model-based sensitivity analysis was performed identifying the critical process parameters to product purity and optimal cut points. From this, the robust fixed cut points were found and pooling control strategies for variations in the critical parameters were designed. Direct measurements and indirect measurements based on the UV detector signal were used as control signals. The method is demonstrated for two case studies of preparative protein chromatography: hydrophobic interaction and reversed phase chromatography. The yield improved from 88.18 to 92.88% when changing from fixed to variable pooling in hydrophobic interaction chromatography, and from 35.15 to 76.27% in the highly sensitive reversed phase chromatography.
Westerberg
Karin
K
Department of Chemical Engineering, Lund University, P.O. Box 124, 22100 Lund, Sweden.
Degerman
Marcus
M
Nilsson
Bernt
B
D000327:Adsorption; D001709:Biotechnology / Q000379:methods*; D002138:Calibration; D002845:Chromatography / Q000379:methods*; D003198:Computer Simulation; D000431:Ethanol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007074:Immunoglobulin G / Q000737:chemistry; D007328:Insulin / Q000737:chemistry; D007700:Kinetics; D015233:Models, Statistical; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013269:Stochastic Processes
D007074:Immunoglobulin G; D007328:Insulin; D012710:Serum Albumin, Bovine; D000431:Ethanol