Virus validation of plasma-derived products produced by Pharmacia, with particular reference to immunoglobulins.

Abstract

Important factors to assure the safety of plasma-derived products manufactured on an industrial scale are initial screening of the source material and validation of the manufacturing process in accordance with issued EEC guidelines and US [Points to Consider'. Pharmacia's manufacturing process for immunoglobulins contains a specific virucidal step, in which lipid-enveloped viruses are effectively inactivated with a solvent/detergent (SD) combination consisting of 0.3% tri(n-butyl)phosphate and 1% Tween 80. Results from virus validation studies of scaled-down versions of Pharmacia's manufacturing process for immunoglobulins demonstrated extensive removal of relevant and model viruses. More than 5.0 logs of human immunodeficiency virus type 1 (HIV-1) were inactivated in the SD step and, in total, more than 31 logs of HIV-1 were eliminated in the steps studied. Comparison between SD treatment and heating at 60 degrees C of lipid-enveloped viruses in different protein solutions demonstrated that SD treatment is the superior procedure. Polio virus is a model often used in virus validation studies to predict effects on non-enveloped viruses. Because polio virus is more sensitive to heat than are hepatitis A virus (HAV) and human parvovirus B19, thermal inactivation studies with polio virus may result in an overestimation of the effects on HAV and B19.