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The value of non-human primates in the development of monoclonal antibodies

Nature Biotechnology volume 31, pages 882–883 (2013)Cite this article

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To the Editor:

Ever since the first recombinant biologics came on the market in the 1980s, it was clear that nonclinical safety programs used to assess the safety and efficacy of small-molecule therapeutics would not be appropriate for this new class of products1. This eventually led to the publication of an international guideline specifically for the development of biotech products called the International Conference on Harmonization S6 (ICH S6; ref. 2). In contrast to nonclinical testing of small molecules, where an extensive set of guidelines covers the nonclinical testing program, ICH S6 offers a flexible, science-based and case-by-case approach that exploits characteristics exclusive to biotech products. For one, binding of biotech products to their target is highly species specific. Therefore, ICH S6 supports testing in only one relevant species if this can be scientifically justified. This often leaves the non-human primate (NHP) that possesses the relevant target antigen as the only available model for nonclinical testing. However, from a scientific point of view, the use and predictive power of NHPs is questionable3. Their use also poses ethical, practical and financial hurdles. Despite these quandaries, NHP use in drug development has been increasing substantially over the years. Solid scientific data are urgently needed for an informed debate on the future of NHPs in the development of biotech products. Here, we present a report on a comprehensive study of the value of NHP data in the nonclinical assessment of monoclonal antibodies (mAbs). Uniquely, through the databases of the Medicines Evaluation Board in Utrecht, The Netherlands, we had access to drug registration files with every animal study done to support marketing authorization of all mAbs approved in the European Union (EU; Brussels) to date (a full set of results will be published elsewhere).

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Figure 1: Average use of NHP per nonclinical programs increases as the mAb in development becomes more human.

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Acknowledgements

This research is part of Top Institute Pharma project T6-301. P.J.K.v.M. and M.K. performed this work with the TIP grant. The views expressed in this article are the personal views of the authors and are not to be understood or quoted as being made on behalf of or reflecting the position of the Medicines Evaluation Board or any other regulatory agency, or one of its committees or working parties.

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Authors and Affiliations

  1. Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    P J K van Meer & H Schellekens

  2. Copernicus Institute of Sustainable Development, Innovation Studies, Utrecht University, Utrecht, The Netherlands

    M Kooijman, E H M Moors & H Schellekens

  3. Medicines Evaluation Board, Utrecht, The Netherlands

    J W van der Laan

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  1. P J K van Meer
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Correspondence to P J K van Meer.

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Competing interests

H.S. participated in meetings and publications sponsored by Amgen, J&J, Roche, Sandoz and Hospira. Part of his research is also directly or indirectly sponsored by Amgen, Roche and Sandoz.

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van Meer, P., Kooijman, M., van der Laan, J. et al. The value of non-human primates in the development of monoclonal antibodies. Nat Biotechnol 31, 882–883 (2013). https://doi.org/10.1038/nbt.2709

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