VI process
The VI operation included acidification (VIA) and neutralization (VIN)
steps. At the VIA step, 0.1 N HCl (pH 1.0, density of 0.9998 g
ml-1, and viscosity of 1.022 mPa
s-1) was added to PAE until reaching pH 3.5-3.8. The
acidified PAE was held for a minimum of 60 min to inactivate virus. At
the following VIN step, 2 M Tris-Base (pH 11.2, density of 1.056 g
ml-1, and viscosity of 1.871 mPa
s-1) was added to the VIA pool until reaching pH
5.3-5.7. The VIN pool was held at 4 oC overnight prior
to purification. The subsequent downstream purification steps reduced
the HMW level from a maximum of 3.5% in the VIN pool to < 1%
in the drug substance to meet the product specification. For process
robustness, the in-process criterion for the VIN pool HMW level
(HMW%, VIN) was < 2.5% with 1% safety
margin.