Establishment of European Pharmacopoeia BRP batch 2 for inactivated poliomyelitis vaccine for in vitro D antigen assay.

Abstract

A collaborative study was initiated by the European Directorate for the Quality of Medicines (EDQM) to assign a potency value for the candidate Ph Eur BRP batch 2 against the 2nd International Standard (IS) in order to replace the dwindling stocks of Ph Eur BRP batch 1. The candidate material is a concentrated trivalent bulk (Type 1 (Mahoney), Type 2 (MEF1) and Type 3 (SAUKETT)) from a commercially available IPV vaccine. Nine laboratories participated in the collaborative study. Eight laboratories reported results. Participants performed in-house ELISA assays on the candidate BRP, the 2nd International Standard (IS) and the current BRP (BRP batch 1). An additional sample was included to acquire information on the correlation between the in vitro and in vivo assays based on comparison with a previous study. Results of that comparison are included as an annex. Potency estimates were satisfactory in terms of repeatability and reproducibility, however the estimates for the 2nd IS were significantly lower than those for Ph Eur BRP batch 1. These two reference standards are derived from the same material and were originally assigned the same potency value after a joint study run by EDQM and the WHO in 1994. A reconciliation study was therefore designed to determine if the IS stored at NIBSC and the IS which had been sent from NIBSC to EDQM for use in the initial study were equivalent. 3 of the laboratories from the initial study participated. Results revealed no significant difference between the 2nd IS stocks stored in the two different locations at NIBSC nor between BRP batch 1 and the standards stored at NIBSC for types 1 and 2. For type 3 the 2nd IS standards stored at NIBSC are 13 % less potent than the Ph Eur BRP batch 1. The 2nd IS which had been shipped from NIBSC to EDQM was significantly less potent than BRP batch 1 and the 2nd ISs stored at NIBSC for all three types, confirming the observation of the initial study. Possible explanations for this apparent loss of potency of the 2nd IS used in the study are under investigation. Since Ph Eur BRP batch 1 and the 2nd IS in stock at NIBSC appear no more different than when their original potency assignment was made at their establishment, and since the 2nd IS standard used in the initial part of this study was compromised, a consensus potency value for the candidate BRP was determined using Ph Eur BRP batch 1 as the reference standard. The candidate material was therefore assigned a potency of 320-67-282 D Antigen units/ml (IU) for types 1, 2 and 3 respectively. A stability monitoring program will be initiated. The candidate material was adopted by the European Pharmacopoeia Commission at its session in March 2003 as European Pharmacopoeia IPV vaccine BRP batch 2 for D Ag in vitro assay.