Joint WHO/EDQM Collaborative study for the establishment of WHO 3rd International Standard and Ph. Eur. Biological Reference Preparation for Prekallikrein activator in albumin batch 7.

Abstract

An international collaborative study was jointly organised by the World Health Organization (WHO) and the European Directorate for the Quality of Medicines & HealthCare (EDQM) to establish the WHO 3^rd International Standard (IS) for Prekallikrein activator (PKA) and European Pharmacopoeia (Ph. Eur.) PKA in albumin Biological Reference Preparation (BRP) batch 7. Twenty-six laboratories took part in the study to calibrate these replacement batches, as well as an additional reserve batch for the WHO IS, against the current WHO 2^nd IS for PKA (02/168). Ph. Eur. PKA in albumin BRP batch 6 was also included to evaluate the continuity of the consecutive batches of BRP. The centrally calculated overall Huber's means based on the results from laboratories with at least two valid assays were 29.6 and 29.6 IU/ampoule for the candidate WHO 3^rd IS (Sample A) and reserve batch (Sample B), and were 38.4 and 37.0 IU/vial for the current BRP batch 6 (Sample C) and the candidate BRP batch 7 (Sample D). The intra-laboratory variation expressed as coefficient of variation (CV) ranged between 1.4 and 16.6 %. The inter-laboratory variation expressed as CV based on Huber's means ranged between 4.4 and 5.4 %. The Huber's mean activity of Sample D against Sample C was 36.6 IU/vial with a CV of 1.7 %. These results confirm the good continuity of the consecutive batches of BRP. Based on the results of this study, it is recommended to establish Sample A as the WHO 3^rd IS for PKA with an assigned potency of 30 IU/ampoule and Sample D as the Ph. Eur. PKA in albumin BRP batch 7 with an assigned potency of 37 IU/vial. Sample B is intended to be kept as a future reserve replacement WHO IS.