spargers), gas flow rate, stirrer configuration, and stirrer type and use of pumps

(perfusion mode) optimal mixing conditions need to be found.

When multiple impellers are mounted on the stirrer shaft of larger bioreactors the

respective types can be combined and the direction of mounting the impeller also

needs to be considered. For bioreactors with baffles stirring will likewise need to be

adapted. In small bioreactors, some sensors or tubes might even function like baffles.

As shown in Figure 5.5, flat blade or rushton turbine, pitched blade, marine

impeller, axial flow blade, or propeller three blade can be used. Depending on the

blade type either axial or radial flow will develop.

In spinner flasks (non-controlled small-scale STRs), especially for microcarrier

cultivation, additional stirrers are used, such as pendular stirrers or stirrer units that

are covered by silicone tubings for bubble-free aeration. Also paddle impellers and

plough impellers can be obtained, particularly in disposable bioreactors. In all

STRs, in particular glass and stainless steel bioreactors, the position of the impellers

and stirring direction needs to be adapted to the filling height and cultivation need.

Disposable stirred tank bioreactors are typically preconfigured and cannot be

modified as easy. Furthermore, it seems not always trivial to position the stirrer

shaft correctly in larger bags (the largest disposable STR currently available is

5,000 L (Thermo Fischer Scientific S.U.B.)). This issue could be avoided by using

OSBs that are available up to 2,500 L.

5.6.2

PROCESS VARIABLES

Physicochemical variables play an important role in cell culture performance and

virus production. Options for monitoring and control depend strongly on the built-in

capacities of the bioreactor systems.

Propeller

Rushton blade

Attributes

Axial

Radial

Gassing

Less suitable

Highly suitable

Dispersing

Less suitable

Highly suitable

Suspending

Highly suitable

Less suitable

Blending

Highly suitable

Suitable

Baffles

Highly suitable

Less vortex, less swirl

Shear

More shear

More shear

Other types

Marine impeller,

pitched blade

Scada, Rushton 4-blade,

pitched blade

FIGURE 5.5 Possible flow of impellers: axial or radial flow. Adapted from: [ 53].

Upstream processing for viral vaccines

105