Chinese Hamster Ovary (CHO) cells are widely used for biopharmaceutical production due to their ability to produce complex therapeutic proteins, such as IgG monoclonal antibodies (mAbs). Monoclonal antibodies make up a significant portion (approximately 50% to 60%) of all biologics, and the vast majority of these (around 70%) are produced in CHO cells. CHO cells are the preferred system for mAbs because they provide the necessary post-translational modifications, such as N-linked glycosylation, for this class of proteins.
CHO cell lines are also well established, with optimised protocols and extensive regulatory approvals, making them the industry standard for antibody production. Significant improvements have been made to mAb productivities from CHO systems, with fed-batch systems typically achieving 2-7 g/L, and even higher yields possible from perfusion systems. These improvements have been achieved through advances in cell line engineering, the development of serum-free and chemically defined media, and improvements in bioreactor design and monitoring systems.
Not suited to other biologics
However, while these advances have made CHO the leading platform for manufacturing mAbs and complex biologics with N-linked glycosylation, they do not necessarily translate to other biologics, where the factors described above are worth considering when selecting the most appropriate expression system. It is generally more advantageous to deploy microbial systems for biologics manufacture when suitable options exist due to the higher costs and complexity required for CHO systems.
Lengthy cell line development and slow growth rates
CHO cells have relatively slower growth rates, which can prolong production timelines, making the g/L supernatant yields irrelevant when comparing total plant output per annum. Developing CHO cell lines that produce the desired product can take months or even years, and the subsequent optimisation of growth conditions, stability, and productivity is also time-consuming. Although CHO is relatively efficient at glycosylation, the glycosylation patterns are not identical to human cells, which can impact the efficacy or immunogenicity of the final product. CHO cells are also susceptible to contamination by adventitious agents, including viruses, so rigorous testing and viral clearance procedures are required, adding to production costs and complexity. While scalable, CHO still requires significant infrastructure and production costs are high for large-scale production due to the need for complex growth media and facilities.
