title: BAY 81-8973, a full-length recombinant factor VIII: manufacturing processes and product characteristics.
abstract: BAY 81-8973 (Kovaltry®, Bayer, Berkeley, CA, USA) is an unmodified, full-length recombinant human factor VIII (FVIII) approved for prophylaxis and on-demand treatment of bleeding episodes in patients with haemophilia A. The BAY 81-8973 manufacturing process is based on the process used for sucrose-formulated recombinant FVIII (rFVIII-FS), with changes and enhancements made to improve production efficiency, further augment pathogen safety, and eliminate animal- and human-derived raw materials from the production processes. The baby hamster kidney cell line used for BAY 81-8973 was developed by introducing the gene for human heat shock protein 70 into the rFVIII-FS cell line, a change that improved cell line robustness and productivity. Pathogen safety was enhanced by including a 20-nm filtration step, which can remove viruses, transmissible spongiform encephalopathy agents and potential protein aggregates. No human- or animal-derived proteins are added to the cell culture process, purification or final formulation. The BAY 81-8973 manufacturing process results in a product of enhanced purity with a consistently high degree of sialylation of N-linked glycans on the molecular surface. The innovative manufacturing techniques used for BAY 81-8973 yield an effective rFVIII product with a favourable safety profile for treatment of haemophilia A.
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Garger
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Severs
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Regan
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hesslein
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ignowski
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Long
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Bayer, Berkeley, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
mesh_terms: D005169:Factor VIII / Q000378:metabolism*; D006031:Glycosylation; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: C427184:recombinant factor VIII SQ; D005169:Factor VIII
keywords: BAY 81-8973; HSP70 heat shock protein; factor VIII; glycosylation; haemophilia A