title: 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.
authors.affiliation: Pharmacia AB, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Eriksson
authors.forename: L
authors.initials: L
authors.lastname: Westman
authors.forename: M
authors.initials: M
authors.lastname: Jernberg
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D003257:Consumer Product Safety; D006361:Heating; D006801:Humans; D007136:Immunoglobulins / Q000009:adverse effects / Q000096:biosynthesis* / Q000627:therapeutic use; D010755:Organophosphates / Q000494:pharmacology; D010949:Plasma / Q000187:drug effects / Q000821:virology*; D011136:Polysorbates / Q000494:pharmacology; D012107:Research Design; D014777:Virus Diseases / Q000517:prevention & control / Q000635:transmission*
chemical_list: D000998:Antiviral Agents; D007136:Immunoglobulins; D010755:Organophosphates; D011136:Polysorbates; C009524:tributyl phosphate