Transferring a biologic candidate from the research and development phase to commercial production usually requires increasing the working volume of the upstream bioprocess. During scale-up, process performance optimised at a small scale needs to be reproduced at a larger scale, ideally without much need for process optimisation at large working volumes. This requires reproducing the cells’ growth environment across scales. In this article Amanda Suttle, Ulrike Rasche, and Ma Sha at Eppendorf discuss why certain bioreactors’ engineering parameters are critical to making this possible.
Extract:
‘From R&D to Production: How the Bioreactor Choice Can Streamline Biologics Scale-Up’
Transferring a biologic candidate from the research and development phase to commercial production usually requires increasing the working volume of the upstream bioprocess. During scale-up, process performance optimised at small scale needs to be reproduced at larger scale, ideally without much need for process optimisation at large working volumes. This requires reproducing the cells’ growth environment across scales. In this article we discuss why certain bioreactors’ engineering parameters are critical to make this possible and demonstrate, how we scaled-up a cell culture process for mAB production from research to pilot production scale, using single-use bioreactors at all stages.
Developing new biologics in a commercially viable manner requires monitoring of development costs and time to market. An integral part of biologics manufacturing is the upstream bioprocess, during which cells are multiplied in bioreactors and allowed to express the protein of interest. Process scale-up strongly determines upstream bioprocess performance. To achieve this goal, streamlined process transfer is implemented to reproduce the product titers and quality which have been optimised in small working volumes at production scale.
Can we reproduce the cells’ growth environment at different scales?
Various parameters define the cells’ growth environment in a stirred-tank bioreactor, such as the concentration and distribution of nutrients, the dissolved oxygen concentration, and shear stress. These parameters relate to the bioreactor’s capabilities: Gassing devices, gas flow, and culture mixing influence the DO and shear conditions. The culture mixing determines the distribution of nutrients.
To streamline scale-up, bioengineers commonly use bioreactors with similar geometries at all scales and keep one or more physicochemical parameters constant between vessels of different sizes, such as the volumetric mass transfer coefficient (kLa), power input per volume, tip speed or mixing time.
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