Choosing the right cell culture technologies is an essential element in process development. Stirred tank and wave bioreactors each have unique advantages for different applications. Discover the parameters you should consider for your bioprocess.
In upstream bioprocesses, the cell line properties, metabolism, and activity; process parameters; and media components work together to influence the productivity and quality of the product. Searching for the best bioreactor technology and optimal conditions for your cell line may require extensive parameter control to maximize productivity and cell viability.
There are two types of advanced technologies for bioreactor cell cultures: rocking motion and stirred tank bioreactors.
A rocking motion bioreactor is based on wave-mixed technology for mixing and oxygen transfer in suspension cell cultures.An inflated 2Dsingle-use bag is attached to a motorized platform that creates a rocking motion to induce waves in media, keeping the cells in suspension and aerating the culture.
A stirred tank bioreactor usually consists of a tubular vessel design with a defined height-to-diameter dimension ratio.The mixing is carried out by a central stirring element inside the culture vessel, leading to an optimal distribution of nutrients and gases inside the vessel. The stirred tank design has long been the gold standard for stainless steel bioreactors and is still implemented for most single-use bioreactor systems.
Both rocking motion and stirred tank technologies are suitable for a range of cells, including CHO, HEK293, stem cells, and CAR-T cells. Since rocking motion bioreactors do not use submerged gassing or stirrer elements, they provide a gentle environment for all cell types. This is especially useful for shear-sensitive cells, such as endothelial cells, and unstable products, such as bioconjugates.
Rocking motion technology is suitable for working volumes of 0.1 L-100 L while stirring motion single-use technologies are suitable for up to 2,000 L. Stirred tank bioreactors are well known for excellent scalability, as constant geometry parameters enable simplified design space transfer even for demanding processes. Consequently, this results in reduced time and effort for process development.
Rocking motion perfusion bags are well suited to simplify process intensification using an integrated cell retention device. Rocking motion technology can be integrated as part of a seed train process to ensure maximum cell culture viability and high-density inoculation of the production bioreactor (Picture 1). This strategy can reduce production bioreactor culture days by up to 20%.
Single-use bioreactors are increasingly being adopted in biopharmaceutical manufacturing owing to their relative ease of use, cost-savings, and positive impact on both facility flexibility and process robustness. Both rocking motion and stirred tank bioreactor technologies are compatible with single-use culture vessels.
Regardless of the cell culture technology selected, process monitoring and control are essential to maximizing the quality and consistency of cell cultures and final products. The outstanding control offered by process analytical technologies (PATs), such as the BioPAT® range of sensors and analyzers (Process Analytical Technology), provide real-time data to promote high-quality production and optimal compliance.
The stirred tank design has long been the gold standard for stainless steel bioreactors and is still followed for most single-use bioreactor systems. However, wave-mixing technology can be a good alternative for shear-stress-sensitive cell lines and make an excellent addition to a productive, intensified seed train.
Consider and weigh the above factors before deciding which technology to implement into your process.
The article was downloaded and translated from the official Sartorius website.