A Collaborative Study to Establish the 6^th International Standard for Factor VIII Concentrate

 

 Buy Article Permissions and Reprints

Summary

A study was carried out to replace the 5^th WHO International Standard (IS) for factor VIII concentrate, because of depletion of stocks. Two candidate concentrates (X and Y) were assayed as potential replacements against the 5^th IS for FVIII concentrate, in a collaborative study involving 33 laboratories. Collaborators were asked to use the ISTH/SSC recommendations, including pre-dilution of concentrates in FVIII deficient plasma in their assays. Several laboratories performed more than one assay method and altogether there were 21 sets of assays with the one-stage method, 6 with the two-stage method and 26 with the chromogenic method. There was good agreement between laboratories using each method for the comparison of concentrates X and Y against the 5^th IS, but the overall potencies by one-stage and chromogenic methods each differed by approximately 5% from the overall mean, with the chromogenic potency approximately 10% higher than the one-stage. Inter-laboratory agreement was slightly better for concentrate Y than X, and stability studies indicated that Y was more stable than X. After considering all the information, together with comments from participants and from the FVIII/FIX Subcommittee of the ISTH/SSC, candidate Y (NIBSC code [97/616]), was proposed and accepted in October, 1998, by the Expert Committee on Biological Standardisation of the World Health Organisation to be the 6^th International Standard for Factor VIII Concentrate with an assigned potency of 8.5 IU/ampoule.

• References

• 1 Bangham DR, Biggs R, Brozovic M, Denson KWE, Skegg JL. A biological standard for measurement of blood coagulation factor VIII activity. Bull WHO 1971; 45: 337-51.
  PubMedGoogle Scholar
• 2 Barrowcliffe TW, Kirkwood TBL. An international collaborative assay for factor VIII clotting activity. Thromb Haemost 1978; 40: 261-72.
  PubMedGoogle Scholar
• 3 Barrowcliffe TW, Curtis AD, Thomas DP. Standardisation of factor VIII. IV. Establishment of the 3^rd international standard for factor VIII:C concentrate. Thromb Haemost 1983; 50: 697-702.
  Article in Thieme ConnectPubMedGoogle Scholar
• 4 World Health Organization.. Tech Rep Ser 1990; 800: 9.
  PubMed
• 5 World Health Organization.. Tech Rep Ser 1995; 858: 15.
  PubMed
• 6 Barrowcliffe TW. Factor VIII and Factor IX Sub-committee. Recommendations for the assay of high purity factor VIII concentrates. Thromb Haemost 1993; 70 (Suppl. 05) 876-7.
  Article in Thieme ConnectPubMedGoogle Scholar
• 7 Barrowcliffe TW. Standardization and Assay. Semin Thrombos Hemostas 1993; 19: 73-9.
  PubMedGoogle Scholar
• 8 Finney D. Statistical method in biological assay. Charles Griffin; London: 1978
  Google Scholar
• 9 Kirkwood TBL. Geometric means and measure of dispersion. Biometrics 1979; 35: 908-9.
  PubMedGoogle Scholar
• 10 Kirkwood TBL, Tydenham MS. Design and analysis of accelerated degradation tests for the stability of biological standards. J Biol Stand 1984; 12: 195-224.
  CrossrefPubMedGoogle Scholar
• 11 Kirkwood TBL, Barrowcliffe TW. Discrepancy between 1-stage and 2-stage assay of factor VIII:C. Br J Haematol 1978; 40: 333-8.
  CrossrefPubMedGoogle Scholar
• 12 Barrowcliffe TW, Kemball-Cook G, Heath AB. Proposed 5^th international standard for factor VIII concentrate. NIBSC unpublished report 1994
  PubMedGoogle Scholar
• 13 Barrowcliffe TW, Raut S, Hubbard AR. Discrepancies in potency assessment of recombinant FVIII concentrates. Haemophilia 1998; 4: 634-40.
  CrossrefPubMedGoogle Scholar
• 14 Albertengo ME, Barrowcliffe TW, Oliva L, Bevan S, Raut S. New recombinant standard for FVIII concentrate gives same results as previous plasma derived standards on a range of FVIII products. Thromb Haemost 2000; 83: 789-90.
  Article in Thieme ConnectPubMedGoogle Scholar