title: The manufacturing process for B-domain deleted recombinant factor VIII.
abstract: The development of a cell bank used in the routine manufacturing of a B-domain deleted recombinant coagulation factor VIII (BDDrFVIII) molecule involved stable insertion of the human BDDrFVIII gene into Chinese hamster ovary (CHO) cells, selection of a cell line capable of expressing consistent levels of active BDDrFVIII, and the establishment of a cell bank. The manufacturing process begins with the culturing of CHO cells in large bioreactors. Product synthesis is initiated by altering the cell culture conditions, thereby arresting the cells in a stationary growth phase and inducing elevated expression of BDDrFVIII. Harvested culture medium is concentrated by chromatography and then purified through a series of four column chromatography steps and one solvent-detergent virus inactivation step. By eliminating the presence of human serum albumin in the final formulation, the BDDrFVIII-containing coagulant product meets with a high standard of safety against microbial and viral contamination. Extensive studies have shown that BDDrFVIII is a consistent, highly pure factor VIII for the treatment of patients with hemophilia A.
authors.affiliation: Pharmacia AB, Stockholm, Sweden.
authors.forename: R K
authors.initials: RK
authors.lastname: Eriksson
authors.forename: C
authors.initials: C
authors.lastname: Fenge
authors.forename: E
authors.initials: E
authors.lastname: Lindner-Olsson
authors.forename: C
authors.initials: C
authors.lastname: Ljungqvist
authors.forename: J
authors.initials: J
authors.lastname: Rosenquist
authors.forename: A L
authors.initials: AL
authors.lastname: Smeds
authors.forename: A
authors.initials: A
authors.lastname: östlin
authors.forename: T
authors.initials: T
authors.lastname: Charlebois
authors.forename: M
authors.initials: M
authors.lastname: Leonard
authors.forename: B D
authors.initials: BD
authors.lastname: Kelley
authors.forename: A
authors.initials: A
authors.lastname: Ljungqvist
mesh_terms: D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular / Q000379:methods; D006224:Cricetinae; D005169:Factor VIII / Q000096:biosynthesis* / Q000302:isolation & purification*; D006801:Humans; D008420:Manufactured Materials / Q000592:standards
chemical_list: C427184:recombinant factor VIII SQ; D005169:Factor VIII