Combining Mechanistic Modeling and Raman Spectroscopy for Monitoring Antibody Chromatographic Purification

Autor: Martin F. Luna, Massimo Morbidelli, Alessandro Butté, Simone Garbellini, Hervé Broly, Sebastian Vogg, Fabian Feidl, Jonathan Souquet
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Processes
Volume 7
Issue 10
Processes, Vol 7, Iss 10, p 683 (2019)
Processes, 7 (10)
ISSN: 2227-9717
DOI: 10.3390/pr7100683
Popis: 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.
Processes, 7 (10)
ISSN:2227-9717
Databáze: OpenAIRE