title: The manufacturing process for recombinant factor IX.
abstract: 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.
authors.affiliation: Genetics Institute, Inc, Andover, MA 01810, USA.
authors.forename: S
authors.initials: S
authors.lastname: Harrison
authors.forename: S
authors.initials: S
authors.lastname: Adamson
authors.forename: D
authors.initials: D
authors.lastname: Bonam
authors.forename: S
authors.initials: S
authors.lastname: Brodeur
authors.forename: T
authors.initials: T
authors.lastname: Charlebois
authors.forename: B
authors.initials: B
authors.lastname: Clancy
authors.forename: R
authors.initials: R
authors.lastname: Costigan
authors.forename: D
authors.initials: D
authors.lastname: Drapeau
authors.forename: M
authors.initials: M
authors.lastname: Hamilton
authors.forename: K
authors.initials: K
authors.lastname: Hanley
authors.forename: B
authors.initials: B
authors.lastname: Kelley
authors.forename: A
authors.initials: A
authors.lastname: Knight
authors.forename: M
authors.initials: M
authors.lastname: Leonard
authors.forename: M
authors.initials: M
authors.lastname: McCarthy
authors.forename: P
authors.initials: P
authors.lastname: Oakes
authors.forename: K
authors.initials: K
authors.lastname: Sterl
authors.forename: M
authors.initials: M
authors.lastname: Switzer
authors.forename: R
authors.initials: R
authors.lastname: Walsh
authors.forename: W
authors.initials: W
authors.lastname: Foster
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D005164:Factor IX