TY - RPRT T1 - Collaborative Study for the Validation of Alternative in vitro Potency Assays for Human Tetanus Immunoglobulin Y1 - 2009 A1 - Gross,S. A1 - Janssen,S.W.J A1 - de Vries,B A1 - Terao,E. A1 - Daas,A. A1 - Buchheit,K.H. KW - 2009 KW - a KW - additional KW - Agreement KW - ALL KW - alternative KW - an KW - analysi KW - analysis KW - AS KW - at KW - blood KW - Control KW - Correlation KW - council of europe KW - Countries KW - data KW - Design KW - Development KW - EIA KW - estimation KW - Europe KW - European KW - European Commission KW - Group KW - guidance KW - Human KW - Immunoassay KW - Immunoglobulin KW - Immunoglobulins KW - in vivo KW - Industries KW - Industry KW - International KW - IS KW - IT KW - Laboratories KW - MEDIA KW - method KW - methods KW - ON KW - ph KW - PRODUCTS KW - programme KW - public KW - Quality KW - QUALITY ASSURANCE KW - Quality Control KW - Reproducibility KW - result KW - results KW - Sample KW - Samples KW - State KW - States KW - study KW - System KW - Term KW - Test KW - TESTING KW - Tetanus KW - time KW - Validate KW - VALIDATION KW - values KW - work AB - The European Pharmacopoeia (Ph. Eur.) monograph Human tetanus immunoglobulin (0398) gives a clear outline of the in vivo assay to be performed to determine the potency of human tetanus immunoglobulins during their development. Furthermore, it states that an in vitro method shall be validated for the batch potency estimation. Since no further guidance is given on the in vitro assay, every control laboratory concerned is free to design and validate an in-house method. At the moment there is no agreed in vitro method available. The aim of this study was to validate and compare 2 alternative in vitro assays, i.e. an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), through an international collaborative study, in view of their eventualinclusion into the Ph. Eur.. The study was run in the framework of the Biological Standardisation Programme (BSP), under the aegis of the European Commission and the Council of Europe.The collaborative study reported here involved 21 laboratories (public and industry) from 15 countries. Initially, 3 samples with low, medium and high potencies were tested by EIA and TIA. Results showed good reproducibility and repeatability of the 2 in vitro methods. The correlation of the data with the in vivo potency assigned by the manufacturers however appeared initially poor for high potency samples. Thorough re-examination of the data showed that the in vivo potencies assigned by the manufacturers had to be corrected: one for potency loss at the time of invitro testing and one because of a reporting error. After these corrections the values obtained by in vivo and in vitro methods were in close agreement. A supplementary collaborative work was carried out to validate the 2 methods for immunoglobulin products with high potencies. Eight laboratories (public and industry) took part in this additional study to test 3 samples with medium and high potencies by EIA and TIA. Results confirmed that the 2 alternative methods are comparable in terms of assay repeatability, precision and reproducibility. In all laboratories, both methodsdiscriminated between the low, medium and high potency samples. Analysis of the data collected in this study showed a good correlation between EIA and TIA potency estimates as well asa close agreement between values obtained by in vitro and in vivo methods. The study demonstrated that EIA and TIA are suitable quality control methods for polyclonal human tetanusimmunoglobulin, which can be standardised in a quality control laboratory using a quality assurance system. Consequently, the Ph. Eur. Group of Experts 6B on Human Blood and Blood products decided in April 2009 to include both methods as examples in the Ph. Eur. monograph 0398 on Human Tetanus immunoglobulin. PB - European Directorate for the Quality of Medicines & HealthCare (EDQM) Council of Europe CY - Strasbourg, France VL - 2009-1 U1 - 4829 ER -