WHO/BS/2019.2365 WHO 1st IS for Adalimumab

Overview

Stocks of the existing WHO 3rd International Standard (IS) for Streptokinase are low and a replacement is required. Two candidate replacements were donated by manufacturers and formulated, filled and freeze-dried into sealed glass ampoules (coded 16/356 (sample B) and 16/358 (sample C)). An international collaborative study was organised to assign potency values to the candidate standards relative to the current IS (00/464, sample S). A fourth sample (88/824, sample A) used in the previous two international collaborative studies to establish the 2nd and 3rd IS, was also included.

A total of 15 laboratories from 9 countries were recruited to take part in the study, all of which returned results, using chromogenic and/or fibrinolytic methods. Assays from each laboratory were used to calculate laboratory geometric mean potencies, which were combined to give overall geometric mean potencies for each method. There was very good agreement between the methods, which were combined to give overall potencies of 909.1 IU/ampoule for 16/356 and 1012.7 IU/ampoule for 16/358, from a total of 69 independent assays. Interlaboratory variability, expressed as the geometric coefficient of variation (GCV), was 8.2 % and 7.2 % for 16/356 and 16/358, respectively. The potency obtained for 88/824 (461 IU/ampoule, GCV = 11.3 %) was the same as the result obtained in 2000 to establish the 3rd IS, suggesting excellent long-term stability of the material and good continuity of the unit. Accelerated degradation studies on 16/356 and 16/358 indicate the candidate standards are very stable, in agreement with results for previous streptokinase standards.