WHO/BS/2017.2309 Report on a Collaborative Study for Proposed Candidate 1st IS for the biological activities of Rituximab

Overview

A candidate rituximab preparation was formulated and lyophilised at NIBSC prior to evaluation in a collaborative study for its suitability to serve as an international standard for the biological activities of rituximab. The candidate was tested at the collaborating laboratories alongside a coded duplicate, a second rituximab lyophilised preparation and the laboratory’s in house reference standard when available. The preparations were tested for their complement dependent cytotoxic activity (CDC) by sixteen laboratories and their antibody dependent cytotoxic activity (ADCC) were tested by eleven laboratories. Different in vitro cell-based bioassays were used in the study as per collaborator qualified methodologies. A limited number of laboratories also performed cell-based antibody binding and apoptosis assays.

The results suggest that the candidate preparation coded as NIBSC 14/210 is suitable to serve as an international potency standard for rituximab. In general, the potency estimates were in poor agreement when expressed relative to the in house reference standards with the greatest variability between laboratories observed for the ADCC assay. However, the data show that the use of the candidate international standard helps with harmonising the reporting of rituximab bioactivities by different laboratories using their in house potency assays for each of the activities studied, namely CDC, ADCC and cell binding.