title: A world-wide survey and field study in clinical haemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE.
abstract: BACKGROUND
  Discrepancies have been previously reported for one-stage clotting and chromogenic assays for FVIII activity analysis. Inter-laboratory variations in instruments, method of clot detection, assay set-up, reference standard calibration, reagent source and reagent composition all contribute to assay variability.
  
  
  OBJECTIVE
  To characterise multilaboratory assay variability in measuring ADYNOVATE, OBIZUR and ADVATE FVIII activity in human plasma and survey multinational FVIII activity assay preferences.
  
  
  METHODS
  As samples from patients treated with either of the FVIII products are not available in the quantities required for a systematic collaborative study, haemophilia A plasma was spiked in vitro with either ADYNOVATE (PEGylated rFVIII), OBIZUR [Porcine Sequence Antihaemophilic Factor (Recombinant)] or ADVATE at high (0.80 IU or U mL-1), medium (0.20 IU or U mL-1) and low (0.05 IU or U mL-1) FVIII concentrations, based on labelled potencies. Clinical laboratories used their routine FVIII activity assay to determine FVIII activity of each product. Thirty-five data sets using one-stage clotting assay and 11 sets using chromogenic assay were obtained.
  
  
  RESULTS
  A vast majority of laboratories (98%) prefer and rely on the one-stage clotting assay. Mean recoveries across all concentrations were 113%, 120% and 127% for ADYNOVATE, OBIZUR and ADVATE respectively. Assay variation was comparable between ADVATE, ADYNOVATE and OBIZUR with inter-laboratory percent coefficients of variation (%CV) ranging from 11 to 22%. Mean chromogenic assay results were 116%, 51% and 113% for ADYNOVATE, OBIZUR and ADVATE respectively. Inter-laboratory CV's were similar for ADYNOVATE, OBIZUR and ADVATE.
  
  
  CONCLUSIONS
  One-stage clotting assays can and will be used with sufficient accuracy and precision for the measurement of ADYNOVATE, OBIZUR and ADVATE in plasma samples from subjects with haemophilia A. Chromogenic assay underestimates OBIZUR potency, particularly at lower concentrations.
authors.affiliation: Baxalta, Vienna, Austria.
authors.forename: P L
authors.initials: PL
authors.lastname: Turecek
authors.affiliation: Baxalta, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Romeder-Finger
authors.affiliation: Baxalta, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Apostol
authors.affiliation: Baxalta, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Q2 Solutions, Rosebank, Livingston, UK.
authors.forename: A
authors.initials: A
authors.lastname: Crocker-Buqué
authors.affiliation: Quintiles, Biostatistics, Bloemfontein, South Africa.
authors.forename: D A
authors.initials: DA
authors.lastname: Burger
authors.affiliation: Quintiles, Biostatistics, Bloemfontein, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Schall
authors.affiliation: Baxalta, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Gritsch
mesh_terms: D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000628:therapy*; D006487:Hemostasis / Q000276:immunology*; D006801:Humans; D008297:Male; D011795:Surveys and Questionnaires
chemical_list: D005169:Factor VIII
keywords: 
  PEG FVIII
  ; FVIII assay; acquired haemophilia; chromogenic assay; haemophilia; one-stage clotting assay; porcine FVIII