Collaborative study for the establishment of Golimumab Biological Reference Preparation Batch 1.

A candidate preparation of the fully human anti-tumour necrosis factor (TNF) monoclonal antibody golimumab was formulated and lyophilised at the Medicines and Healthcare products Regulatory Agency (MHRA) prior to evaluation in a collaborative study for its suitability to serve as a World Health Organization (WHO) International Standard (IS)/European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for the potency assay of golimumab. Fifteen laboratories tested the preparations using different cell-based TNF-α neutralisation assays. Among them, seven laboratories also performed binding assays and one additional laboratory assessed antibody-dependent cellular cytotoxicity. The results of this study and the stability data generated by the MHRA indicated that the candidate preparation, coded 22/116, was suitable to serve as an IS for golimumab based on the data obtained for biological activity. This candidate standard was established in 2024 as the first IS for golimumab with an assigned potency of 500 IU per ampoule for TNF neutralising activity. In the same study, the suitability of this preparation of golimumab to serve as the Ph. Eur. BRP for the golimumab potency assay, as described in the Ph. Eur. monographs on Golimumab injection (3187) and Golimumab concentrated solution (3103), was also evaluated. The corresponding analysis, based on the measurement of the inhibitory action of golimumab on the cytotoxic activity of TNF-α, was performed using data from a subset of six laboratories - whose experts were members of the P4 Biologicals Working Party (responsible for the elaboration of the golimumab monographs) - using the TNF-α-sensitive mouse fibrosarcoma cell lines WEHI-164 or WEHI-164 clone 13 variant (WEHI-13VAR, ATCC CRL-2148) in example bioassay procedure(s) described in Ph. Eur. monographs 3103 and 3187, or running the same cell-based assays using in-house procedures. The results obtained were compared with those obtained from different cell-based neutralisation assays that were used by other laboratories in the context of establishing the 1st WHO IS for golimumab. Based on the analyses, preparation 22/116 was adopted by the Ph. Eur. Commission in June 2024 as Golimumab BRP batch 1 with an assigned potency of 500 IU of TNF neutralising activity per ampoule.