Significant improvements in the productivity and quality of therapeutic proteins produced in Chinese hamster ovary (CHO) cells have been reported since their establishment as host cells for biopharmaceutical production. Initial advances in the field focused on engineering strategies to manipulate genes associated with proliferation, apoptosis, and various metabolic pathways. Process engineering efforts to optimize culture media, batch-feeding strategies and culture conditions, including temperature and osmolarity, were also reported. More recently, focus has shifted toward enhancing process consistency and product quality using systems biology quality by design-based approaches during process development. Integration of different data generated using omics technologies, such as genomics, transcriptomics, proteomics and metabolomics, has facilitated a greater understanding of CHO cell biology. These techniques have enabled the provision of global information on dynamic changes in cellular components associated with different phenotypes. Using systems biology to understand these important host cells at the cellular level will undoubtedly result in further progression in the development and expression of biopharmaceutical products in CHO cells.

Large-scale chromatography operations continue to occupy a key position in the overall strategy for the downstream processing and purification of protein products for therapeutic use. Increasing product titres from mammalian cell culture has resulted in a trend to identify ways of improving the economics of product recovery and purification processes. In commercial manufacturing, a requirement exists to increase the scale of the chromatography operations, which are typically developed and optimised in small-scale experiments. This short review discusses the key factors in the chromatography process that need to be considered as the scale of the purification step is increased in order to maintain the purity and integrity of the product purified at smaller scale.

Separation science continues to occupy the central position in the overall strategy for the downstream processing and purification of therapeutic protein products for human use. Increasing product titers from mammalian cell culture and new emerging classes of biopharmaceuticals has presented a challenge to the industry to identify ways of improving the robustness and economics of chromatography processes. In commercial manufacturing, there is always a need to increase the scale of the chromatography operations which are typically developed and optimized in small-scale laboratory experiments. This review discusses the key factors in the chromatography process that need to be considered as the scale of the purification step is increased in order to maintain the purity and integrity of the product purified at smaller scale.