Calibration of the Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) standard for human coagulation factor VIII concentrate for use in the potency assay.

ABSTRACT

The European Pharmacopoeia Biological Reference Preparation Batch 3/Mega 2 (United States/Food and Drug Administration) (Ph. Eur. BRP Batch 3/Mega 2 (US/FDA)) was developed as an internationally available, common working standard to replace the dwindling stocks of Mega 1 (the current US standard) and Ph. Eur. BRP Batch 2 (the current European standard). The potency was assigned in an international collaborative study with reference to four currently established standards, Ph. Eur. BRP batch 2, WHO 5th and 6th International Standard and Mega 1. Thirty-eight laboratories participated in the collaborative study. Each laboratory was asked to perform four independent assays. Participants used either the one stage clotting assay or the chromogenic assay or both. This publication reports the results obtained with both assays. The summary and conclusion, however highlight the results mainly with respect to the chromogenic assay, which is the assay prescribed in the European Pharmacopoeia. Data were analysed for both assays separately. A consensus potency value was calculated as the unweighted average of mean potencies determined against the four standards. A potency of 8.6 IU/vial as determined in the chromogenic substrate method was assigned to the candidate standard. Inter-laboratory agreement as assessed by calculation of the geometric coefficient of variation was below 10% for mean potencies against all four calibrators for the chromogenic assay. Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) is a freeze-dried, plasma derived, high-purity concentrate. The material was filled into approximately 100,000 vials and lyophilised to a final residual moisture of < or = 2%. Approximately 90,000 vials of the standard are available, equally shared between the two co-ordinating centers. Based on the stability studies, the predicted mean percentage loss per year at -20 degrees C is 0.000% and thus the candidate standard appears to be stable. The Ph. Eur. BRP batch 3 was adopted by the European Pharmacopoeia Commission in November 2001.