Monoclonal antibodies (mAbs) are complex proteins that specifically react with sites, or epitopes, on target molecules. They have become important research tools and are also a highly successful class of biological drugs. The therapeutic monoconal antibody field continues to expand and mAbs are already an integral part of healthcare systems around the world with products available to treat cancer, inflammation, autoimmunity and infectious disease. With the expiry of some patents on early ‘blockbuster’ drugs, drug manufacturers are increasingly interested in developing ‘biosimilars’. Some biosimilar mAbs have already been approved for use and the number of available biosimilar mAbs is expected to continue to grow over the next few years.
Monoclonal antibody standards for bioassays and reference reagents
Centrally authorised products (CAP) testing of mAbs
We also participate in expert working groups at European and international level (EDQM and WHO).Biotherapeutic monoclonal antibody products authorized in Europe and related advances in antibody technologies
MAbs are complex and heterogeneous biological medicines. Current regulatory approval of biosimilar mAb products involves exhaustive comparability studies with the originator product (reference medicinal product) to demonstrate biosimilarity.
With an increase in the number of biosimilars available and under development, there is a need for primary reference standards for biological activity. These preparations are stable and publically available standards that further contribute to ensuring product consistency, quality, safety and efficacy. Endorsed by WHO, we are committed to developing international standards (IS) for a number of mAbs including rituximab, trastuzumab, cetuximab, infliximab, adalimumab and bevacizumab.
International multicentre collaborative studies have already shown the benefits of these reagents to harmonise potency data for Infliximab and Rituximab. By defining international units (IU) of bioactivity, these standards can support the performance and calibration of bioassays and in-house standards over long periods of time.
The distinct roles of the WHO international standard and the reference medicinal productPipeline of monoclonal antibody (mAb) standards
The structure of IgG and typical forms of monoclonal antibody (mAb) heterogeneity (post-translational modifications and degradation) and mechanisms of action. The mechanism of action of biotherapeutic mAbs are modulated by their structural characteristics and isotype form. A and B illustrate the CDC activity of 3 rituximab preparations (samples A-C) and the rituximab international standard (NIBSC 14/210) and the relative CDC activity of rituximab and obinutuzumab, respectively. Panel C shows the ADCC activity of the NIBSC 14/210 rituximab IS preparation during thermal degradation stability studies and panel D shows the relative ADCC activity of two deglycosilated rituximab variants.
Dr Simon E. HuftonDr Sandra PriorChristine BallDr Carl DolmanDr Meenu WadhwaBernard FoxDr Melissa HaymanPaul RisleyWalter RamageDr Clive MetcalfeDr Haiyan JiaChris Bird