Establishing a large number of media components, media design manufacturers spend a lot of effort and time on this activity. The role of supplements that increase productivity and regulate the quantity and quality of recombinant protein products is critical in media optimization to reduce the production of unwanted metabolites. A deeper understanding of metabolic and cellular mechanisms is needed to define strategies that provide effective means to reduce by-products and improve the quality and yield of biologics.
CHO cells are the primary production host cells for recombinant protein production due to their adaptability to various culture conditions and plasticity relative to genetic alterations, contributing to the development of biopharmaceutical processes to improve the production of CHO-based organisms through cell line engineering, improved cell growth-based approaches, upregulation of post-translational modifications through targeted approaches at the genomic and cellular levels, and enhanced protein stability. Cell culture media are known to significantly affect cell culture performance, downstream processing, and the quality of the product. Substantial progress has been made in this area. In this article, we review how media composition regulates the quality of recombinant protein products and explore the relationship between media design and CQA.
The formulation of quality cell culture media is an important activity in process development. In the absence of a common procedure, traditional optimization methods, such as titration of individual components or "one component at a time" method, are useful but can be labor- and time-consuming. Screening the experimental design with these components in the low and high concentration ranges can help determine which components have a significant impact on productivity and quality.
The Design of Experiments (DoE) approach is effective for experimental screening of these factors. During this activity, changes in the osmolality concentration of the molecules of the medium and the production of metabolic waste should be carefully monitored. Amino acids promote cell growth and productivity. They are a source of nitrogen, a building block of proteins, and mediating intermediates in a variety of metabolic pathways. Amino acid supplementation is considered to be one of the important components of cell culture media design and optimization.
