would allow for continuous virus harvest, which has been shown to have potential

advantages. For example, Gränicher et al. (2020) demonstrated an increase of CSVY

of at least 1.5 through continuous removal of IAVs using an acoustic settler compared

to an ATF system [50]. Whether continuous harvest of virus particles with short RTs

or retention within the bioreactor during the whole production phase is beneficial

depends on the virus and has to be evaluated beforehand [29].

6.6.1

SPIN FILTERS

Spin filters were first introduced as a cell retention device for HCD cultivations of

mammalian suspension cells by Himmelfarb et al. in 1969 [64]. Here, a cylindrical

membrane placed inside or outside the bioreactor is rotated around the same axis as the

impeller (see Figure 6.4). Rotation is initiated either by mounting the spin filter on

the impeller shaft or an independent motor [53]. Cell-free permeate is pumped into the

cylinder and removed through the harvest line while cells are retained in the vessel,

outside of the spin filter by the membrane. There are two major differences between

spin filters and other cross-flow filters. First, the rotation of the cylinder is used to create

a fluid flow relative to the filter surface which is placed inside the bioreactor. Therefore,

the cells remain in a controlled environment, the retentate cell concentration is

Feed pump

Balance

Weight control

Permeate pump

Spent medium

Feed

medium

FIGURE 6.4 Schematic illustration of a spin filter setup. Cell-free supernatant is constantly

removed from the interior of the cylindrical spin filter, allowing fresh medium to be added to

the bioreactor. Cells are retained on the outside of the cylinder. In this setup, impeller and

filter rotate independently. Figure adapted from [ 65].

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Bioprocessing of Viral Vaccines