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Maintaining ‘standards’ for biosimilar monoclonal antibodies

Nature Biotechnology volume 39, pages 276–280 (2021)Cite this article

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Biological medicines cannot be adequately characterized by physicochemical analysis alone11, and expression of potency in units of bioactivity relative to an independent standard is an essential regulatory tool for harmonizing patient dosing. ISs have long provided a mechanism to assign biological potency to many biological products and to maintain a global system of secondary standards12,13. Biotherapeutic mAbs are biotech-derived products; unlike traditional biologicals, they have no natural equivalent, and ISs do not exist during the development of a novel innovative mAb. Consequently, when a single new product is alone on the market, its bioactivity is described in the manufacturer’s proprietary units and the licensing authorities permit dosing and labeling in mass units.

In contrast, when biosimilar products enter the market, an IS is needed to ensure harmonized measurement of biological activity, in the same way as for naturally derived biologicals. In recognition of this, the Expert Committee on Biological Standardization has established the first World Health Organization (WHO) ISs for rituximab, infliximab, adalimumab, bevacizumab and trastuzumab14,15,16,17,18 and endorsed several other programs for the standardization of mAbs19,20.

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Fig. 1: Biosimilar product approvals.
Fig. 2: The development and use of manufacturer’s in-house bioassay reference standards, the RMP and WHO IS at different stages of the life cycle of mAb products.
Fig. 3: The different and unique roles and characteristics of the RMP, manufacturer’s in-house reference standards and the WHO IS for mAbs.

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Acknowledgements

The authors wish to thank the Scientific Advice, Human Medicines Research & Support Division from the EMA for providing the information on the Scientific Advice procedures used in Supplementary Fig. 1. This paper is based on independent research commissioned and funded by the NIHR Policy Research Programme (NIBSC Regulatory Science Research Unit). The views expressed in the publication are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, ‘arms-length’ bodies or other government departments.

The National Institute for Biological Standards and Control (NIBSC) is a center of the Medicines and Healthcare Products Regulatory Agency, an Agency of the UK Government’s Department of Health and Social Care. It fulfills its public health role through the standardization and control of biologicals used in medicine. NIBSC’s strategy includes anticipating emerging quality and safety issues associated with existing and future biological medicines, and facilitation of the development of novel biological medicines and diagnostics. In some instances, it is appropriate for NIBSC to charge commercial and other organizations for its products and services, in line with guidance issued from Her Majesty’s Treasury (‘Fees & Charges Guide’ and ‘Selling into Wider Markets’). NIBSC endeavors to make the same products and services equally available to commercial organizations, without prejudice.

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Authors and Affiliations

  1. National Institute for Biological Standards and Control (NIBSC), South Mimms, United Kingdom

    Sandra Prior, Clive Metcalfe, Simon E. Hufton, Meenu Wadhwa, Christian K. Schneider & Chris Burns

  2. Twincore Centre, Hannover Medical School, Hannover, Germany

    Christian K. Schneider

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  1. Sandra Prior
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Correspondence to Sandra Prior.

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Supplementary Fig. 1 and Supplementary Tables 1 and 2

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Prior, S., Metcalfe, C., Hufton, S.E. et al. Maintaining ‘standards’ for biosimilar monoclonal antibodies. Nat Biotechnol 39, 276–280 (2021). https://doi.org/10.1038/s41587-021-00848-0

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