New WHO International Standards for monoclonal antibody therapies 

The National Institute for Biological Standards and Control (NIBSC) have established World Health Organization (WHO) International Standards for the biological activity of monoclonal antibody products, rituximab and infliximab. 

The highly stable lyophilised preparations aim to support manufacturers and regulators with the calibration and validation of bioassays and in-house standards.  

When tested in independent collaborative studies,involving more than 15 international laboratories, both standards were able to harmonise reporting of rituximab and infliximab bioactivity in a number of cell-based tests. 

Standards to support product consistency

Monoclonal antibodies are large, complex proteins that can be sensitive to small changes arising from variations during the manufacturing process. 

Strict regulation of the manufacture and quality of mAb products is therefore necessary before products can be released onto the market. 

For biosimilars, products must also undergo extensive comparison with the ‘original’ product, known as the reference medicinal product, to demonstrate biosimilarity.  

Collaborative study data showed that both standards were able to improve the consistency of bioactivity results between different laboratories in in vitro bioassays including antibody dependent cellular cytotoxicity, complement dependent cytotoxicity and binding assays for rituximab, and anti-TNFα neutralisation and binding assays for infliximab. The infliximab standard is also recommended for use in therapeutic drug monitoring assays.

Dr Sandra Prior, Senior Scientist in the Division of Biotherapeutics at NIBSC said:

“Over time small drifts in the product can occur, so it’s essential to have a consistent way of measuring the biological activity of mAb products across laboratories.Our standards harmonise the performance and calibration of bioassays used at different stages of the product lifecycle, including those used in the comparability studies with the original reference product.”

been applied to support the development of other complex protein products derived from DNA recombinant technologies, for example with the establishment of the WHO International Standards for pegfilgrastim and etanercept.

Responding to a growing market

Monoclonal antibodies have revolutionised the treatment of many important diseases in oncology and inflammation and in 2016, made up over 5 of the top best-selling drugs that year. As patents for the original products expire, manufacturers can now develop new biosimilar medicines for popular therapeutic mAbs.

Dr Meenu Wadhwa, Section Leader in the Division of Biotherapeutics at NIBSC comments:

“The expiry of patents is leading to the rapid growth of mAb biosimilars for a range of indications including autoimmune diseases and oncology, which helps to improve affordability and access to these essential medicines. With support from WHO, we’re continuing to develop our range of standards to other mAb products such as adalimumab, trastuzumab, cetuximab and bevacizumab to ensure the provision of safe and effective medicines globally”.

"Therapeutic drug monitoring (TDM) assays are currently gaining momentum as a tool for patient management, helping to identify patients eligible for dose reduction or increase, treatment termination or switching within, or out-of-class. Extending the use of the infliximab standard for the standardisation of TDM assays will support clinical decision-making where possible and facilitate the efficacy and cost-effectiveness of therapeutic biological medicines.”

To find out more about upcoming mAb standards projects or to donate candidate material or participate in an upcoming collaborative study contact enquiries@nibsc.org.