Combining Mechanistic Modeling and Raman Spectroscopy for Monitoring Antibody Chromatographic Purification
Abstract
Chromatography is widely used in biotherapeutics manufacturing, and the corresponding underlying mechanisms are well understood. To enable process control and automation, spectroscopic techniques are very convenient as on-line sensors, but their application is often limited by their sensitivity. In this work, we investigate the implementation of Raman spectroscopy to monitor monoclonal antibody (mAb) breakthrough (BT) curves in chromatographic operations with a low titer harvest. A state estimation procedure is developed by combining information coming from a lumped kinetic model (LKM) and a Raman analyzer in the frame of an extended Kalman filter approach (EKF). A comparison with suitable experimental data shows that this approach allows for the obtainment of reliable estimates of antibody concentrations with reduced noise and increased robustness. Show more
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https://doi.org/10.3929/ethz-b-000378842Publication status
publishedExternal links
Journal / series
ProcessesVolume
Pages / Article No.
Publisher
MDPISubject
Raman spectroscopy; downstream processing; chromatography; flow cell; extended Kalman filterOrganisational unit
03451 - Morbidelli, Massimo (emeritus) / Morbidelli, Massimo (emeritus)
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