Porcine factor VIII: current status and future developments.
High-purity porcine factor VIII (pFVIII) (Hyate:C, Ipsen, UK), with a specific activity of > 125 U mg(-1) protein, has been shown to be effective in up to 90% of bleeds in patients with FVIII inhibitors. These inhibitors have been shown to have a median 15% cross-reactivity to pFVIII, and even less cross-reactivity in patients with acquired haemophilia. Its use is sometimes associated with a transient fall in platelet count and with transfusion reactions. Furthermore, it is not virally attenuated. Although pFVIII has not been shown to transmit any viral illness to its human recipients, it is extensively screened for porcine viruses using a 4-cell line general screen. The source plasma is also screened for porcine parvovirus. To satisfy the demand for ever-improved side-effect profile and viral safety a third-generation pFVIII is under consideration by Ipsen. This product will be purified from porcine plasma screened for porcine parvovirus, using immuno-purification, ion-exchange chromatography and washing. Spiking experiments using human FVIIIC (hFVIIIC) suggest that these purification steps may be associated with a 6-log viral reduction. The product is also virally attenuated using the solvent-detergent method. This should yield an ultra-pure concentrate, lacking porcine von Willebrand factor, with a specific activity of approximately 5000 U mg(-1) protein which does not require added albumin as stabilizer and which may be stored at 2-4 degrees. One would anticipate that this product should be clinically effective and should be associated with enhanced viral safety and an improved side-effect profile. It should not affect the platelet count and should be associated with a much reduced risk of transfusion reactions. Clinical trials are planned.
Hay
C R M
CR
University Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. haemophilia@man.ac.uk
D000818:Animals; D000906:Antibodies / Q000097:blood; D003257:Consumer Product Safety; D004340:Drug Contamination / Q000517:prevention & control; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007263:Infusions, Parenteral / Q000009:adverse effects; D013242:Sterilization / Q000639:trends; D013552:Swine
D000906:Antibodies; D005169:Factor VIII