title: Calibration of replacement international standard and European Pharmacopoeia Biological Reference Preparation for Diphtheria Toxoid, Adsorbed.
abstract: We report here the characterisation of a preparation of diphtheria toxoid, adsorbed, and its calibration by twenty laboratories in fourteen countries in terms of the Second International Standard (I.S.) for Diphtheria Toxoid, Adsorbed, coded sample A (DIXA) using the established World Health Organisation (WHO)/European Pharmacopoeia (Ph Eur) challenge methods. The replacement standard preparation was found to have a unitage of 160 IU/ampoule on the basis of its calibration by in vivo bioassay. Stability was assessed within the collaborative study, and as part of candidate characterisation. Results suggest that the replacement standard will have satisfactory stability. This study also provided an opportunity to investigate serology as alternative to in vivo bioassay for potency testing of diphtheria vaccines. Six laboratories participated by performing serology according to in-house protocol. The calibration of the replacement standard in a mouse Vero cell assay gave a significantly higher results than in the established WHO/Ph Eur methods. Based on the results of this study and with the agreement of participants, the candidate standard was established as the Third International Standard for Diphtheria Toxoid, Adsorbed (coded 98/560) by the WHO Expert Committee of Biological Standardization in October 1999. The same preparation was also established as the second Ph Eur Biological Reference Preparation (Ph Eur BRP, batch no. 3) by the Steering Committee of the Biological Standardisation Programme of the European Directorate for the Quality of Medicines and approved by the European Pharmacopoeia Commission.
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK. dsesardic@nibsc.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Sesardic
authors.forename: R
authors.initials: R
authors.lastname: Winsnes
authors.forename: P
authors.initials: P
authors.lastname: Rigsby
authors.forename: R
authors.initials: R
authors.lastname: Gaines-Das
mesh_terms: D000327:Adsorption; D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D001681:Biological Assay; D002522:Chlorocebus aethiops; D004168:Diphtheria Toxoid / Q000032:analysis / Q000276:immunology / Q000302:isolation & purification / Q000592:standards*; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005612:Freeze Drying; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010602:Pharmacopoeias as Topic; D012015:Reference Standards; D014709:Vero Cells; D014944:World Health Organization
chemical_list: D000942:Antigens, Bacterial; D004168:Diphtheria Toxoid