The manufacturing process for B-domain deleted recombinant factor VIII.
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.
Eriksson
R K
RK
Pharmacia AB, Stockholm, Sweden.
Fenge
C
C
Lindner-Olsson
E
E
Ljungqvist
C
C
Rosenquist
J
J
Smeds
A L
AL
östlin
A
A
Charlebois
T
T
Leonard
M
M
Kelley
B D
BD
Ljungqvist
A
A
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
C427184:recombinant factor VIII SQ; D005169:Factor VIII