Chromatography is widely used in biotherapeutics manufacturing, and the corresponding\nunderlying mechanisms are well understood. To enable process control and automation, spectroscopic\ntechniques are very convenient as on-line sensors, but their application is often limited by their\nsensitivity. In this work, we investigate the implementation of Raman spectroscopy to monitor\nmonoclonal antibody (mAb) breakthrough (BT) curves in chromatographic operations with a low titer\nharvest. A state estimation procedure is developed by combining information coming from a lumped\nkinetic model (LKM) and a Raman analyzer in the frame of an extended Kalman filter approach (EKF).\nA comparison with suitable experimental data shows that this approach allows for the obtainment of\nreliable estimates of antibody concentrations with reduced noise and increased robustness.
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