UF membranes can be manufactured using various polymers, including polysulfone

(PS), regenerated cellulose (RC), polyethersulfone (PES), and polyvinylidene fluoride

(PVDF).

A good solution for concentration and diafiltration of viruses is the use of low

adsorptive membranes especially in the case of enveloped viruses. As an example,

the biotechnology company Sartorius proposes Hydrosart® cassettes that exhibit a

novel technology based on stabilized cellulose membranes. Such technology en-

ables high flow rates and high product recovery by reducing the fouling effect.

It already showed promising results for adenovirus purification with a recovery of

87% [48]. More recently, this technology has also become available in Sartocon®

ECO format for low shear operations, which is characterized by being extremely

hydrophilic and prone to non-protein binding.

Despite the efforts in developing robust purification processes for viral biother-

apeutics, most of the process development has been focused on chromatographic

steps. However, recently Carvalho et al. developed a fully optimized filtration cascade

process for an influenza vaccine candidate [49]. Several companies are investing

efforts to develop devices suitable for vaccine product candidates, such as Cytiva’s

750 C hollow-fiber membranes. These membranes were optimized to propose a more

open structure, enabling higher removal of host-cell DNA [50].

Another operation mode of ultrafiltration is the single-pass TFF (SPTFF), a

method that enables the concentration of the product of interest in a single pump

pass as an inlet concentration step (Figure 7.4). This technology enables to achieve

high concentration (up to 30 times) and recovery, control, and reduce the in-process

volumes, operating in continuous mode [51]. This technology can be operated either

with cassettes or hollow fibers. In the absence of recirculation, thus applying less

shear stress to the circulating solution, it makes a promising strategy for the fragile

enveloped viruses.

Chromatography is probably the most popular technique of the intermediate

purification step. Separation methods based on chromatography have been used in

the biological field for decades for the purification of recombinant proteins and

(a)

(b)

FIGURE 7.4 Different designs of tangential flow filtration: (a) traditional batch tangential

flow filtration and (b) single-pass tangential flow filtration.

Downstream processing

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