Cultured cells are used for the manufacturing of biologics such as vaccines, therapeutic proteins and antibodies, and cell therapy products. As the need for biologic therapies and vaccines increases, there is increasing interest in establishing more efficient cell culture processes through the development of:
Although bacterial, yeast, and insect cell expressions systems are capable of overexpressing recombinant proteins, mammalian cells are most commonly used for biologics production due to their ability to propagate human viruses, express monoclonal antibodies, and incorporate post-translational modifications such as glycosylation that are critical to the production of effective biologics. Several mammalian cell lines, including CHO, lymphoma (NS0, SP2/0) and human embryonic kidney (HEK) cells, have been developed and used to produce therapeutic proteins and antibodies at high levels. Advances in gene editing such as CRISPR-Cas systems further enhance production efficiency and improve product quality through modification of host cell genomes to manipulate cell growth and apoptosis, and to promote post-translational modification of the gene product.
Culture medium optimization is another critical component in the development of cell culture processes for the manufacturing of biologics. Synthetic cell culture media that are free of serum and animal-derived components are typically used in the production of biologicals to reduce the variability inherent in undefined media and supplements; to eliminate the presence of process contaminants and adventitious agents; and to reduce the risk of unintentional/adverse effects. Because cell lines are unique and require different nutrients to thrive, culture biomass and protein production are largely dependent on the culture media used.
Bioreactors are large scale culture devices used in upstream processes and production that play a key role in expanding and scaling cell culture for production. The typical seed train cell expansion process involves thawing cryopreserved cells followed by successive expansions into larger culture vessels including flasks, spinners, and stirred bioreactors. When culture volume and cell density are optimal, the culture is then transferred to a production bioreactor. Bioreactors provide controlled microenvironments and nutrient delivery to regulate cell growth and differentiation, improving standardization and reproducibility. Stainless steel stirred tank bioreactors are still commonly used for production, though single-use, disposable bioreactors are being employed to enable flexibility and reduce downtime needed for the cleaning and sterilization of traditional permanent equipment.