Simultaneous prediction of 16 quality attributes during protein A chromatography using machine learning based Raman spectroscopy models.

Abstract

Several key technologies for advancing biopharmaceutical manufacturing depend on the successful implementation of process analytical technologies that can monitor multiple product quality attributes in a continuous in-line setting. Raman spectroscopy is an emerging technology in the biopharma industry that promises to fit this strategic need, yet its application is not widespread due to limited success for predicting a meaningful number of quality attributes. In this study, we addressed this very problem by demonstrating new capabilities for preprocessing Raman spectra using a series of Butterworth filters. The resulting increase in the number of spectral features is paired with a machine learning algorithm and laboratory automation hardware to drive the automated collection and training of a calibration model that allows for the prediction of 16 different product quality attributes in an in-line mode. The demonstrated ability to generate these Raman-based models for in-process product quality monitoring is the breakthrough to increase process understanding by delivering product quality data in a continuous manner. The implementation of this multiattribute in-line technology will create new workflows within process development, characterization, validation, and control.