Antihemophilic Factor (Recombinant), Plasma/Albumin-Free, the active ingredient in XYNTHA, is a recombinant coagulation factor VIII produced by recombinant DNA technology for use in therapy of factor VIII deficiency. The Antihemophilic Factor (Recombinant), Plasma/Albumin-Free in XYNTHA is a purified glycoprotein with an approximate molecular mass of 170 kDa consisting of 1438 amino acids, which does not contain the B-domain.¹³ The amino acid sequence of Antihemophilic Factor (Recombinant), Plasma/Albumin-Free in XYNTHA is comparable to the 90 + 80 kDa form of human factor VIII.

The Antihemophilic Factor (Recombinant), Plasma/Albumin-Free in XYNTHA is secreted by a genetically engineered Chinese hamster ovary (CHO) cell line. The cell line is grown in a chemically defined cell culture medium that contains recombinant insulin, but does not contain any materials derived from human or animal sources. The Antihemophilic Factor (Recombinant), Plasma/Albumin-Free in XYNTHA is purified by a process that uses a series of chromatography steps, one of which is based on affinity chromatography using a patented synthetic peptide affinity ligand.¹⁴ The process also includes a solvent-detergent viral inactivation step and a virus-retaining nanofiltration step.

The potency expressed in International Units (IU) is determined using the chromogenic assay of the European Pharmacopoeia. The Wyeth manufacturing reference standard for potency has been calibrated against the World Health Organization (WHO) International Standard for factor VIII activity using the one-stage clotting assay. The specific activity of XYNTHA is 5500 to 9900 IU per milligram of protein.

XYNTHA is formulated as a sterile, nonpyrogenic, preservative-free, freeze-dried powder preparation for intravenous (IV) injection. Each single-use vial contains nominally 250, 500, 1000 or 2000 IU of XYNTHA. Upon reconstitution, the product is a clear to slightly opalescent, colorless solution that contains sodium chloride, sucrose, L-histidine, calcium chloride and polysorbate 80.

REFERENCES

13. Sandberg H, Almstedt A, Brandt J, Castro VM, Gray E, Holmquist L et al. Structural and Functional Characterization of B-Domain Deleted Recombinant Factor VIII. Sem Hematol. 2001;38 (Suppl. 4):4-12.

14. Kelley BD, Tannatt, M, Magnusson, R, Hagelberg S. Development and Validation of an Affinity Chromotography Step Using a Peptide Ligand for cGMP Production of Factor VIII. Biotechnol Bioeng. 2004;87(3):400-412.

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