title: Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII.
abstract: BACKGROUND
  Hemophilia A is routinely treated by administration of exogenous coagulation factor VIII (FVIII). As safety and efficacy of FVIII products have improved over the years, development of FVIII-neutralizing antibodies (FVIII inhibitors) has emerged as the most serious complication. The new human cell line-derived recombinant human FVIII (human-cl rhFVIII) is the first recombinant FVIII product produced in a human cell line without additive animal proteins, with a goal of minimizing the risk of inhibitor development.
  
  
  METHODS
  Biochemical analyzes of purity, molecular and functional attributes of the novel human-cl rhFVIII were undertaken for product characterization.
  
  
  CONCLUSIONS
  Human-cl rhFVIII was shown to be highly pure, with host-cell protein and DNA traces comparable to, or lower than, currently marketed recombinant FVIII (rFVIII) products. Human-cl rhFVIII was shown to have high specific FVIII activity and characteristics similar to full-length rFVIII products. Furthermore, no significant discrepancy between one-stage and chromogenic assay results were observed for human-cl rhFVIII, indicating potency ratios of these assays comparable to the full-length rFVIII products. In functional tests, human-cl rhFVIII exhibited physiological thrombin generation and a normal rate of inactivation by activated protein C. Importantly, human-cl rhFVIII displayed higher binding capacity with von Willebrand factor than comparator products, thus minimizing circulating unbound FVIII and further reducing the potential risk of inhibitor development.
authors.affiliation: Octapharma, Stockholm, Sweden. helena.sandberg@octapharma.se
authors.forename: Helena
authors.initials: H
authors.lastname: Sandberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Kannicht
authors.forename: Peter
authors.initials: P
authors.lastname: Stenlund
authors.forename: Marina
authors.initials: M
authors.lastname: Dadaian
authors.forename: Ulla
authors.initials: U
authors.lastname: Oswaldsson
authors.forename: Carina
authors.initials: C
authors.lastname: Cordula
authors.forename: Olaf
authors.initials: O
authors.lastname: Walter
mesh_terms: D015153:Blotting, Western; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy; D006801:Humans; D011486:Protein C / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012685:Sepharose / Q000737:chemistry; D020349:Surface Plasmon Resonance; D013917:Thrombin / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism
chemical_list: D011486:Protein C; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D005169:Factor VIII; D012685:Sepharose; D013917:Thrombin