Virus inactivation in a factor VIII/VWF concentrate treated using a solvent/detergent procedure based on polysorbate 20.
Treatment with solvent/detergent is a widely used method for ensuring the virus safety of plasma products. In the present study, virus inactivation by a novel solvent/detergent combination, i.e. TnBP (tri-n-butyl phosphate) and polysorbate 20 during the manufacture of the factor VIII/VWF concentrate Optivate has been investigated. The inactivation of most enveloped viruses was rapid, i.e. > 5 log in 2 min, although the inactivation of vaccinia virus was slower, i.e. 4 log in 1h. Virus inactivation was effective over a wide range of conditions, i.e. solvent/detergent concentration, protein concentration and temperature, irrespective of whether tested individually or in combination. This confirms the effectiveness and robustness of this alternative version of the solvent/detergent procedure, and allows appropriate control limits to be set for this manufacturing step. Polysorbate 20 provides an alternative to the non-ionic detergents currently in use with the solvent/detergent procedure.
Roberts
Peter L
PL
Bio Products Laboratory, Research and Development Department, Dagger Lane, Elstree, Hertfordshire WD63BX, UK. peter.roberts@bpl.co.uk
Lloyd
David
D
Marshall
Philip J
PJ
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D011232:Chemical Precipitation; D002522:Chlorocebus aethiops; D003902:Detergents / Q000494:pharmacology*; D004338:Drug Combinations; D004340:Drug Contamination / Q000517:prevention & control; D005169:Factor VIII / Q000138:chemical synthesis / Q000737:chemistry / Q000592:standards*; D010755:Organophosphates / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology*; D012997:Solvents / Q000494:pharmacology; D013696:Temperature; D014709:Vero Cells; D014777:Virus Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D038301:Virus Inactivation; D014841:von Willebrand Factor / Q000138:chemical synthesis / Q000737:chemistry / Q000592:standards*
D003902:Detergents; D004338:Drug Combinations; D010755:Organophosphates; D011136:Polysorbates; D012997:Solvents; C568131:optivate; D014841:von Willebrand Factor; D005169:Factor VIII; C009524:tributyl phosphate