title: International collaborative study to evaluate candidate reference reagents to standardize haemagglutination testing for anti-A and anti-B in normal intravenous immunoglobulin products.
abstract: OBJECTIVE
  The aim of the study was to evaluate, in an international collaboration, three lyophilized intravenous immunoglobulin (IVIG) preparations for their suitability to standardize and control haemagglutination testing for anti-A and anti-B in IVIG products.
  
  
  METHODS
  Twenty-three laboratories tested candidate IVIG reference reagents consisting of a Positive control (07/306), a Negative control (07/308), and a specifically formulated Limit preparation (07/310) to define the maximum (e.g. pharmacopoeial) limits of anti-A and anti-B in IVIG products, where limits are applicable. Laboratories performed direct haemagglutination using papain-treated erythrocytes and/or indirect antiglobulin tests.
  
  
  RESULTS
  For both methods, there was up to 16-fold variation in anti-A and anti-B titres, although there was good agreement over a two-fold titre range for anti-A and anti-B between laboratories for both 07/306 and 07/310 using the direct method. Comparative titration data for 07/306 and 07/310 indicated that the use of a 'Limit' reference reagent would facilitate identification of higher titre batches when the direct haemagglutination method is used.
  
  
  CONCLUSIONS
  The establishment of preparations 07/306, 07/308 and 07/310 as reference reagents by the World Health Organization will facilitate global standardization of haemagglutination tests for anti-A and anti-B, ensure that such tests are sufficiently sensitive and specific, and facilitate identification of batches that exceed maximum recommended levels of anti-A and anti-B. The Commission of the European Pharmacopoeia and the United States Food and Drug Administration have adopted the same reference reagents including the maximal specifications defined by preparation 07/310.
authors.affiliation: Biotherapeutics Group, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, UK. susan.thorpe@nibsc.hpa.org.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Thorpe
authors.forename: B
authors.initials: B
authors.lastname: Fox
authors.forename: G
authors.initials: G
authors.lastname: Sharp
authors.forename: A B
authors.initials: AB
authors.lastname: Heath
authors.forename: M-E
authors.initials: ME
authors.lastname: Behr-Gross
authors.forename: E
authors.initials: E
authors.lastname: Terao
authors.forename: M L
authors.initials: ML
authors.lastname: Virata-Theimer
authors.forename: M W
authors.initials: MW
authors.lastname: Yu
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D005060:Europe; D006386:Hemagglutination Tests / Q000592:standards*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D007202:Indicators and Reagents / Q000592:standards; D007391:International Cooperation; D007518:Isoantibodies / Q000032:analysis*; D012015:Reference Standards; D017186:Titrimetry; D014481:United States; D014486:United States Food and Drug Administration; D014944:World Health Organization
chemical_list: D000017:ABO Blood-Group System; D016756:Immunoglobulins, Intravenous; D007202:Indicators and Reagents; D007518:Isoantibodies