Integration of scale-down experimentation and general rate modelling to predict manufacturing scale chromatographic separations.
Chromatography is an essential downstream processing step in the production of biopharmaceuticals. Here we present an approach to chromatography scale-up using scale-down experimentation integrated with general rate modelling. This type of modelling takes account all contributions to the mass transfer kinetics providing process understanding. The model is calibrated using a 2.5 cm height, 1 ml column and used to predict chromatograms for 20 cm height columns from 40 ml to 160 L volume. Simulations were found to be in good agreement with experimental results. The envisaged approach could potentially reduce the number of experiments, shorten development time and reduce costs.
Gerontas
Spyridon
S
The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1 7JE, UK.
Asplund
Magnus
M
Hjorth
Rolf
R
Bracewell
Daniel G
DG
D000465:Algorithms; D002852:Chromatography, Ion Exchange / Q000379:methods*; D003198:Computer Simulation; D007475:Ion Exchange Resins / Q000737:chemistry*; D007700:Kinetics; D007781:Lactoferrin / Q000302:isolation & purification; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012710:Serum Albumin, Bovine / Q000302:isolation & purification
D007475:Ion Exchange Resins; D012710:Serum Albumin, Bovine; D007781:Lactoferrin