Collaborative study for the establishment of erythropoietin BRP batch 5.

Abstract

The European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for erythropoietin (EPO) is used as a working standard for potency determination of EPO preparations by in vivo bioassay as prescribed in Ph. Eur. monograph 1316 'Erythropoietin concentrated solution'. BRP batch 4 (BRP4) was calibrated in 2014 and its stocks are depleted. The European Directorate for the Quality of Medicines and HealthCare (EDQM) thus endorsed a project (BSP147) to calibrate a replacement batch in International Units against the 3rd WHO International Standard (IS) for erythropoietin, recombinant, for bioassay (11/170). The amount of material contained in the vial of BRP4 greatly exceeded the amount needed for one bioassay, sometimes leading to considerable waste. It was thus decided to prepare a candidate material with a lower EPO content. The collaborative study involved eight laboratories in Europe, the USA and Australia. Based on the outcome of the study, the Ph. Eur. Commission adopted the proposed standard as Erythropoietin BRP batch 5 in June 2018 for use as a reference preparation solely for the polycythaemic and normocythaemic mouse bioassays, with an assigned potency of 2000 IU/ampoule. Furthermore, the potency of BRP batch 4 was confirmed during the study thus warranting a good continuity of the International Unit.