TABLE 7.1

Combination of technologies used for clarification of viral-based vaccines at pilot (1–20 L) or production scale (more than 20 L)

Vaccine

Production

system

Vaccine type

Product

location

Primary clarification

Secondary clarification

References

Hepatitis C

Insect cell culture

Virus-like

particle

Extracellular

0.2 μm hollow fiber cartridges (TFF)

300 kDa cassettes (TFF)

[ 31]

Yellow fever

Vero cell culture

Inactivated virus Extracellular

Sartopure® PP2 (8.0 μm), NFF

Sartoclean® CA (3.0 μm + 0.8

μm), NFF

[ 28]

Rotavirus

Insect cell culture

Virus-like

particle

Intracellular

Centrifugation at 1000 g for 10 min at 4°C Ultracentrifugation 100,000 g for

1 h at 4°C

[ 16]

Influenza virus MDCK cell

culture

Inactivated virus Extracellular

0.65 μm polypropylene depth filter (NFF)

NA

[ 32]

Enterovirus 71

Vero cell culture

Killed virus

Extracellular

0.65 μm filter (NFF)

NA

[ 33]

Rotavirus

Vero cell culture

Live virus

Extracellular

Centrifugation at 2831 g for 30 min and

4424 g for 10 min at 4°C

0.45 μm hollow fiber (TFF)

[ 34]

Poliovirus

Vero cell culture

Inactivated virus Extracellular

Diatomaceous earth filter with 75 μm pore

size, or Millistak + ® C0HC (Depth filter)

0.45 and 0.22 μm filtration (NFF) [ 35]

Rabies

Vero cell culture

Inactivated virus Extracellular

8 μm MF-Millipore™ membrane filter

0.45 μm Durapore® membrane

filter

[ 36]

Hepatitis C

Insect cell culture

Virus-like

particle

Extracellular

Optiscale depth filtration devices with

Polygard® CN membrane material

300 kDa cassettes (TFF)

[ 37]

(Adapted from Ref. [ 25]). NA – Not applied.

Downstream processing

183