title: International collaborative study on the 3rd WHO International Standard for hepatitis B surface antigen.
abstract: The WHO International Standard (IS) for hepatitis B surface antigen (HBsAg) is used to standardize HBsAg assays. Stocks of the 2nd IS for HBsAg are depleted. The proposal to establish its replacement was endorsed by WHO in 2012.
  
  
  
  Preparation of a freeze-dried candidate 3rd IS (NIBSC 12/226); evaluation of its suitability in a WHO international collaborative study; calibration of its potency in International Units (IU).
  
  
  
  The 3rd IS is based on plasma-derived, purified, inactivated HBsAg from Vietnam. Qualitative and quantitative HBsAg assays were used to evaluate 12/226 alongside the 2nd IS and 1st IS. Blinded study samples included a duplicate of 12/226, a negative control and two diluted plasma samples representing hepatitis B virus (HBV) genotypes A and B.
  
  
  
  Twelve laboratories from 9 countries returned 22 data sets from 15 methods. The overall geometric mean potency of 12/226 is 47.3IU/mL (±13% CV) when compared to the 2nd IS with HBV subgenotype A2. The 3rd IS has HBV subgenotype B4 with a heterogeneous HBsAg subtype population of ayw1 and adw2. Some genotype-dependent effects on the inter-laboratory variability were observed but overall mean potencies were virtually identical irrespective of the IS used for calibration. Stability studies indicate that the candidate is stable for long-term use.
  
  
  
  12/226 was established in October 2014 by the WHO Expert Committee on Biological Standardization as the 3rd IS for HBsAg with a potency of 47.3IU per ampoule maintaining the continuity in the standardization of HBsAg assays.
authors.affiliation: Division of Virology, South Mimms, Potters Bar, Herts., EN6 3QG, UK. Electronic address: Dianna.Wilkinson@nibsc.org.
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Wilkinson
authors.affiliation: Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Pia L
authors.initials: PL
authors.lastname: Seiz
authors.affiliation: Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Schüttler
authors.affiliation: Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Gerlich
authors.affiliation: Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Glebe
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D 63225 Langen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Scheiblauer
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D 63225 Langen, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nick
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D 63225 Langen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Chudy
authors.affiliation: Biostatistics National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts., EN6 3QG, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dougall
authors.affiliation: Division of Virology, South Mimms, Potters Bar, Herts., EN6 3QG, UK.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Stone
authors.affiliation: Biostatistics National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts., EN6 3QG, UK.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Heath
mesh_terms: D006509:Hepatitis B / Q000175:diagnosis*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D007391:International Cooperation; D012015:Reference Standards; D012698:Serologic Tests / Q000592:standards*; D014944:World Health Organization
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Assay standardization; HBV diagnostics; HBsAg; WHO international standard