At its 172nd session in March 2022, the European Pharmacopoeia (Ph. Eur.) Commission adopted a new general chapter, Cell-based assay for potency determination of TNF-alpha antagonists (2.7.26), the first of three planned new horizontal standards for monoclonal antibodies (mAbs).
The adoption of the new chapter marks an important milestone in the Ph. Eur. Commission’s efforts to develop – in response to stakeholder demand – a set of widely applicable recommendations for analytical testing strategies that cover the needs of different classes and sub-classes of mAbs. The resulting “horizontal standards” or “performance-based standards” comprise well-defined analytical procedures and tools to control performance and facilitate analytical assessment of key quality attributes of mAbs.
During elaboration, the procedures described in the new general chapter were subjected to extensive and rigorous analytical testing by Ph. Eur. experts from national control laboratories and the Laboratory of the European Directorate for the Quality of Medicines & HealthCare (EDQM). The scientific evidence gathered during this collaborative process was then used to establish well-defined and globally harmonised methodologies, addressing common expectations widely applicable to TNF-alpha antagonist potency determination. The text includes detailed instructions on how to perform four commonly used cell-based assay procedures and universally applicable parameters/criteria to support system and sample suitability testing. It also contains a dedicated section on general recommendations and adjustment of assay conditions that discusses critical aspects contributing to the variability of assay performance. The chapter does not exclude the use of other procedures that are acceptable to the competent authorities.
Cell-based assays are complex procedures that require significant resources to establish and maintain correctly. This new general chapter provides users with analytical tools and practical guidance to further build on and support testing. It will also help establish an accepted and shared analytical language that contributes to standardising the potency determination of TNF-alpha antagonists, both currently available and in the pipeline.
The two existing individual monographs on TNF-alpha antagonists – Etanercept (2895) and Infliximab concentrated solution (2928) – have been revised to create the link between the respective assay/potency sections and general chapter 2.7.26. This provides for a diversified choice of suitable bioassays for potency determination, while reinforcing and maintaining the flexibility already built into the monographs and the use of Ph. Eur. reference standards. Together, the three texts form the Ph. Eur.’s TNF-alpha bioassay package.
These developments are another positive example of the advantages of close collaboration across the scientific community, bringing together Ph. Eur. experts, regulators and manufacturers, and benefiting from continued engagement and enhanced stakeholder support. The Ph. Eur. is advancing in the field of public standard setting for therapeutic mAbs, exploring flexible concepts of standardisation and pursuing its “bottom-up” approach. It continues to do so by leveraging experience gained from product-specific cases to drive general, transversal matters.
The TNF-alpha bioassay package will be published in Ph. Eur. Supplement 11.1, with an implementation date of 1 April 2023.