Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study

Haemophilia. 2017 Jul;23(4):e335-e339. doi: 10.1111/hae.13250. Epub 2017 May 24.

Abstract

Introduction: Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue.

Aim: Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories.

Methods: Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard.

Results: When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard.

Conclusion: In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard.

Keywords: in vitro; blood coagulation; blood coagulation tests; drug monitoring; factor VIII procoagulant activity; haemophilia A.

Publication types

  • Multicenter Study

MeSH terms

  • Biological Assay / standards*
  • Factor VIII / chemistry*
  • Factor VIII / metabolism*
  • Polyethylene Glycols / chemistry*
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / metabolism*
  • Reference Standards
  • Switzerland

Substances

  • Recombinant Proteins
  • Polyethylene Glycols
  • BAX 855
  • Factor VIII