Calibration of European pharmacopoeia biological reference preparation for diphtheria vaccine (adsorbed) batch 4.

ABSTRACT

A collaborative study was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) and the National Institute for Biological Standards and Control (NIBSC) to establish replacement batches of the current World Health Organization (WHO) International Standard (IS) and European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Diphtheria Vaccine (Adsorbed). Two candidates were assayed against the current 3rd IS/BRP batch 3 for Diphtheria Vaccine (Adsorbed) with an assigned potency of 160 IU/ampoule using established WHO/Ph. Eur. challenge methods in guinea pigs as described in the Ph. Eur. general chapter 2.7.6. Assay of diphtheria vaccine (adsorbed). Twenty-one laboratories (regulatory organisations and manufacturers) from 17 countries participated in the study. Two freeze-dried, stabilised diphtheria vaccine (adsorbed) preparations were included in the study Preparation A (07/218) and Preparation B (07/216). As stocks of the 3rd IS were very low, the Diphtheria vaccine (adsorbed) BRP batch 3, which is identical to the 3rd IS but which was kept at the EDQM, was used for the calibration (coded Preparation C). The majority of participants performed 2 independent challenge tests. Five laboratories performed the intradermal challenge test, 16 laboratories performed the systemic challenge test. For Preparation A, the unweighted geometric mean potency estimate (with 95 % confidence limits) for all laboratories that provided valid results (n = 17) was 97.2 (89.5-105.6) IU/ampoule. For systemic challenge assays (n = 14) the unweighted geometric mean potency was 97.0 (88.1-106.7) IU/ampoule. The between-laboratory GCV was 17.4 % for all assays and 18.0 % for systemic challenge assays. There was no significant difference in estimates for intradermal or systemic challenge (p = 0.45). For Preparation B the unweighted geometric mean potency estimate (with 95 % confidence limits) for all laboratories that provided valid results (n = 19) was 213.4 (185.7-245.4) IU/ampoule. For systemic challenge assays (n = 14) the unweighted geometric mean potency was 202.0 (170.4-239.5) IU/ampoule. The between-laboratory GCV was 33.5 % for all assays and 34.3 % for systemic challenge assays. For both preparations there is a good agreement between results obtained from systemic and intradermal challenge methods. Greater between-laboratory variability was observed for systemic assays than for intradermal challenge assays, although the small number of intradermal assays performed in the study makes comparison difficult. The GCV for all assays was 17.4 % for potency estimates of Preparation A and 33.5 % for Preparation B. This compares favourably with the calibration of the current standard where the between-laboratory GCV for all assays was 28.3 %. From the collaborative study both Preparation A and Preparation B appeared suitable to replace the current Diphtheria vaccine (adsorbed) BRP batch 3. Due to the similarity of Preparation A with the current BRP batch 3, the Ph. Eur. Commission adopted Preparation A as Diphtheria vaccine (adsorbed) BRP batch 4 with an assigned potency of 97 IU/ampoule.