Comprehensive modeling of cell culture profile using Raman spectroscopy and machine learning

Abstract

Chinese hamster ovary (CHO) cells are widely utilized in the production of antibody drugs. To ensure the production of large quantities of antibodies that meet the required specifications, it is crucial to monitor and control the levels of metabolites comprehensively during CHO cell culture. In recent years, continuous analysis methods employing on-line/in-line techniques using Raman spectroscopy have attracted attention. While these analytical methods can nondestructively monitor culture data, constructing a highly accurate measurement model for numerous components is time-consuming, making it challenging to implement in the rapid research and development of pharmaceutical manufacturing processes. In this study, we developed a comprehensive, simple, and automated method for constructing a Raman model of various components measured by LC–MS and other techniques using machine learning with Python. Preprocessing and spectral-range optimization of data for model construction (partial least square (PLS) regression) were automated and accelerated using Bayes optimization. Subsequently, models were constructed for each component using various model construction techniques, including linear regression, ridge regression, XGBoost, and neural network. This enabled the model accuracy to be improved compared with PLS regression. This automated approach allows continuous monitoring of various parameters for over 100 components, facilitating process optimization and process monitoring of CHO cells.

Integrating Artificial Intelligence for Academic Advanced Therapy Medicinal Products: Challenges and Opportunities

“…PAT enables real-time process adjustments and consistency between individualized batches [26]. Building upon the principles of PAT, a recent study [27] made significant strides toward enhancing the capabilities of in-line monitoring and process optimization in biomanufacturing. This research introduced a pioneering automated method for creating Raman spectroscopy models using Python and Bayes optimization.…”