title: Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.
abstract: A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.
authors.affiliation: Centeon L.L.C., King of Prussia, Pennsylvania 19406, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Goldsmith
mesh_terms: D000911:Antibodies, Monoclonal; D002846:Chromatography, Affinity / Q000379:methods; D003257:Consumer Product Safety; D007562:Creutzfeldt-Jakob Syndrome / Q000821:virology; D004203:Disinfection / Q000379:methods / Q000592:standards; D005169:Factor VIII / Q000276:immunology* / Q000592:standards*; D006678:HIV; D006518:Hepatitis Viruses; D006801:Humans; D016732:Parvovirus B19, Human; D010949:Plasma / Q000821:virology; D011786:Quality Control; D014019:Tissue Donors
chemical_list: D000911:Antibodies, Monoclonal; D005169:Factor VIII