title: Collaborative study for the validation of alternative in vitro potency assays for human tetanus immunoglobulins.
abstract: An international collaborative study to validate 2 alternative in vitro methods for the potency testing of human tetanus immunoglobulin products was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). The study, run in the framework of the Biological Standardisation Programme (BSP) under the aegis of the European Commission and the Council of Europe, involved 21 official medicines control and industry laboratories from 15 countries. Both methods, an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), showed good reproducibility, repeatability and precision. EIA and TIA discriminated between low, medium and high potency samples. Potency estimates correlated well and both values were in close agreement with those obtained by in vivo methods. Moreover, these alternative methods allowed to resolve discrepant results between laboratories that were due to product potency loss and reporting errors. The study demonstrated that EIA and TIA are suitable quality control methods for tetanus immunoglobulin, which can be standardised in a control laboratory using a quality assurance system. Consequently, the Group of Experts on Human Blood and Blood Products of the European Pharmacopoeia revised the monograph on human tetanus immunoglobulins to include both the methods as compendial alternatives to the in vivo mouse challenge assay.
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Gross
authors.forename: S W J
authors.initials: SW
authors.lastname: Janssen
authors.forename: B
authors.initials: B
authors.lastname: de Vries
authors.forename: E
authors.initials: E
authors.lastname: Terao
authors.forename: A
authors.initials: A
authors.lastname: Daas
authors.forename: K-H
authors.initials: KH
authors.lastname: Buchheit
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods / Q000592:standards; D019411:Clinical Laboratory Techniques / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards; D005060:Europe; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology* / Q000627:therapeutic use; D007391:International Cooperation; D051379:Mice; D010602:Pharmacopoeias as Topic / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D013742:Tetanus / Q000276:immunology* / Q000517:prevention & control; D013745:Tetanus Toxoid / Q000276:immunology* / Q000592:standards / Q000627:therapeutic use
chemical_list: D007136:Immunoglobulins; D013745:Tetanus Toxoid