Model-based analysis and quantitative prediction of membrane chromatography: Extreme scale-up from 0.08 ml to 1200 ml

A model-based approach is presented for quantitatively decoupling the impacts of non-ideal flow and non-ideal binding in membrane chromatography (MC) capsules at different scales. The internal geometry of Sartobind registered capsules with 0.08 ml and 1200 ml membrane volume is reconstructed from MR...

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Bibliographic Details
Published in:Journal of Chromatography A 2014-03, Vol.1332, p.8-13
Main Authors: GHOSH, Pranay, VAHEDIPOUR, Kaveh, LEUTHOLD, Martin, VON LIERES, Eric
Format: Article
Language:English
Subjects:
Binding
Biological and medical sciences
Calibration
Chromatography
Computational fluid dynamics
Decoupling
Dynamical systems
General pharmacology
Mathematical models
Medical sciences
Membranes
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
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Summary:A model-based approach is presented for quantitatively decoupling the impacts of non-ideal flow and non-ideal binding in membrane chromatography (MC) capsules at different scales. The internal geometry of Sartobind registered capsules with 0.08 ml and 1200 ml membrane volume is reconstructed from MRI measurements and manufacturer data. Based on this information, computational fluid dynamics (CFD) simulations are used for computing internal flow patterns of both capsules. Measured breakthrough curves (BTC) under non-binding conditions are used for calibrating PFR and CSTR models of the holdup volumes in the Aekta systems. A suitable binding model is determined and the binding parameters are estimated from binding BTC data of the 0.08 ml capsule. Due to the decoupling of non-idealities, the binding parameters can be directly transferred between the CFD models of both capsules. This advantage is used for quantitatively predicting BTC data of the 1200 ml capsule under binding conditions. The model-based prediction excellently matches with independently measured BTC data, facilitating an extreme scale-up factor of 15,000. The presented approach has previously been shown to be universally applicable to capsules from other vendors with different flow configurations and membrane types.
ISSN:0021-9673
DOI:10.1016/j.chroma.2014.01.047