title: Anti-A and anti-B haemagglutinin levels in intravenous immunoglobulins: are they on the rise? A comparison of four different analysis methods and six products.
abstract: Recent reports of severe haemolytic reactions upon high dose treatment with new generation intravenous immunoglobulins (IVIGs) prompted us to examine the anti-A and anti-B haemagglutinin content of these therapeutics. We compared four different test methods, namely the indirect and direct haemagglutination test as described in the European Pharmacopoiea (Ph. Eur.) and two commercial gelcard systems with the aim to define the most reliable method for a large-scale comparison of different IVIG products. Absolute titres varied when the same samples were analyzed by the four methods, while the relative ranking of six different IVIG preparations representing different manufacturing classes was identical. New generation IVIGs showed 1-2 titre steps higher anti-A titres than the older products. Haemagglutinin titres of all 48 IVIG batches analyzed were within the current Ph. Eur. specification of ≤1:64 when tested by the official pharmacopoeial method. Based on efficiency, reliability and lower costs, the direct gelcard method could be a valid alternative to the official Ph. Eur. method to serve as a limit test. However, due to the highest intermediate precision, the official Ph. Eur. method seems to be most suitable to compare haemagglutinin titres of different IVIG products.
authors: Swissmedic, Swiss Agency for Therapeutic Products, OMCL Biologika, Hallerstrasse 7, CH-3000 Bern 9, Switzerland. Electronic address: caroline.bellac@swissmedic.ch.
authors: C L
authors: CL
authors: Bellac
authors: Swissmedic, Swiss Agency for Therapeutic Products, OMCL Biologika, Hallerstrasse 7, CH-3000 Bern 9, Switzerland.
authors: D
authors: D
authors: Polatti
authors: Swissmedic, Swiss Agency for Therapeutic Products, Market Surveillance, Hallerstrasse 7, CH-3000 Bern 9, Switzerland.
authors: T
authors: T
authors: Hottiger
authors: Swissmedic, Swiss Agency for Therapeutic Products, OMCL Biologika, Hallerstrasse 7, CH-3000 Bern 9, Switzerland.
authors: P
authors: P
authors: Girard
authors: Swissmedic, Swiss Agency for Therapeutic Products, OMCL Biologika, Hallerstrasse 7, CH-3000 Bern 9, Switzerland.
authors: M
authors: M
authors: Sänger
authors: Swissmedic, Swiss Agency for Therapeutic Products, OMCL Biologika, Hallerstrasse 7, CH-3000 Bern 9, Switzerland.
authors: M
authors: M
authors: Gilgen
mesh_terms: D006388:Hemagglutinins / Q000032:analysis*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000032:analysis*; D015203:Reproducibility of Results
chemical_list: D006388:Hemagglutinins; D016756:Immunoglobulins, Intravenous
keywords: Anti-A haemagglutinin; Anti-B haemagglutinin; BSA; European Pharmacopoeia; Haemolysis; IVIG; IgG; Intravenous immunoglobulins; NIBSC; National Institute for Biological Standards and Control; PBS; Ph. Eur.; RBC; Rhesus D-negative, phenotype ccddee; bovine serum albumin; immunoglobulin G; intravenous immunoglobulin; phosphate buffered saline; red blood cells; rr