Cell culture product quality attribute prediction using convolutional neural networks and Raman spectroscopy

Abstract Advanced process control in the biopharmaceutical industry often lacks real‐time measurements due to resource constraints. Raman spectroscopy and Partial Least Squares (PLS) models are often used to monitor bioprocess cultures in real‐time. In spite of the ease of training, the accuracy of the PLS model is impacted if it is not used to predict quality attributes for the cell lines it is trained on. To address this issue, a deep convolutional neural network (CNN) is proposed for offline modeling of metabolites using Raman spectroscopy. By utilizing asymmetric least squares smoothing to adjust Raman spectra baselines, a generic training data set is created by amalgamating spectra from various cell lines and operating conditions. This data set, combined with their derivatives, forms a two‐dimensional model input. The CNN model is developed and validated for predicting different quality variables against measurements from various continuous and fed‐batch experimental runs. Validation results confirm that the deep CNN model is an accurate generic model of the process to predict real‐time quality attributes, even in experimental runs not included in the training data. This model is robust and versatile, requiring no recalibration when deployed at different sites to monitor various cell lines and experimental runs.