The manufacturing process for recombinant factor IX.
Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.
Harrison
S
S
Genetics Institute, Inc, Andover, MA 01810, USA.
Adamson
S
S
Bonam
D
D
Brodeur
S
S
Charlebois
T
T
Clancy
B
B
Costigan
R
R
Drapeau
D
D
Hamilton
M
M
Hanley
K
K
Kelley
B
B
Knight
A
A
Leonard
M
M
McCarthy
M
M
Oakes
P
P
Sterl
K
K
Switzer
M
M
Walsh
R
R
Foster
W
W
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005164:Factor IX / Q000235:genetics* / Q000302:isolation & purification* / Q000592:standards* / Q000627:therapeutic use; D002836:Hemophilia B / Q000188:drug therapy; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000592:standards / Q000627:therapeutic use
D011994:Recombinant Proteins; D005164:Factor IX