Recent Advances in Culture Medium Design for Enhanced Production of Monoclonal Antibodies in CHO Cells: A Comparative Study of Machine Learning and Systems Biology Approaches

The production of monoclonal antibodies (mAbs) using Chinese Hamster Ovary (CHO) cells has revolutionized the treatment of numerous diseases, solidifying their position as a cornerstone of the biopharmaceutical industry. However, achieving maximum mAb production while upholding strict product quality standards remains a significant hurdle. Optimizing cell culture media emerges as a critical factor in this endeavor, requiring a nuanced understanding of the complex interplay of nutrients, growth factors, and other components that profoundly influence cellular growth, productivity, and product quality. Significant strides have been made in media optimization, including techniques such as media blending, one factor at a time, and statistical design of experiments approaches. The present review provides a comprehensive analysis of the recent advancements in culture media design strategies, focusing on the comparative application of systems biology (SB) and machine learning (ML) approaches. The applications of SB and ML in optimizing CHO cell culture medium and successful examples of their use are summarized. Finally, we highlight the immense potential of integrating SB and ML, emphasizing the development of hybrid models that leverage the strengths of both approaches for robust, efficient, and scalable optimization of mAb production in CHO cells. This review provides a roadmap for researchers and industry professionals to navigate the complex landscape of mAb production optimization, paving the way for developing next-generation CHO cell culture media that drive significant improvements in yield and productivity.