Scalability—an important aspect in bioprocessingSeveral factors play a role in a reliable bioprocess scale-up [1, 2]. Kinetics and thermodynamics are virtually unaffected by the reaction volume. However, the mass transfer within a process is highly dependent on the scale. The geometries of the bioreactor and the impeller influence the mixing time and as such the oxygen uptake, substrate supply of a culture and the reagents addition for e.g. pH-control just as the agitation speed and gassing rate do. Standardized bioreactor formats, in terms of height-to-diameter ratio for example, can contribute to a proper scale-up.
The simple way—not always the best oneDue to their low cost and easy handling, traditional shake flasks and microtiter plates are still widely used in early bioprocess development. However, these tools are poorly instrumented and offer very limited monitoring and control possibilities. Moreover, the hydrodynamics of shaken cultures completely differ from stirred-tank cultures in larger scale bioreactors. Such early-stage cultivation systems are not representative of stirred-tank bioreactor environments, and are therefore not suitable for the development of industrial production processes.
A reliable scale-up strategy is better to count on miniaturized stirred-tank bioreactors, which are comparable with large-scale production reactors in terms of design and fluid dynamics.
Parameters to rely on—conventional scale-up criteriaEngineering parameters such as the vessel and impeller geometry, tip speed, mixing time, oxygen transfer rate, volumetric mass transfer coefficient (kLa), or power number can be used as scale-up criteria . The general strategy is to keep a specific process parameter constant throughout the scale-up process. In this way, negative effects caused by changing environmental conditions during scale-up are minimized. Choosing the best scale-up criterion to use depends on the process.
For cultures that are sensitive to shear force damage, like animal or stem cell cultures, a defined tip speed may be reasonable. On the other hand, such a strategy may limit the working volume because a constant tip speed is achieved by reducing the agitation speed with increasing impeller diameter, thus causing poorer mixing performance in larger vessels.