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Assessing drug safety in human tissues — what are the barriers?

Nature Reviews Drug Discovery volume 14, pages 585–587 (2015)Cite this article

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The drug development process is long and expensive. High attrition rates due to safety liabilities observed in the clinic, but that were not identified during nonclinical development, are a major contributor to the escalating costs and reduced productivity of the industry (Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discov. 14, 248–260 (2015))1. This has called into question the utility of current preclinical safety-testing paradigms — which rely predominantly on animal models, including rodents, dogs and non-human primates — and led to demands for more-predictive tools.

The development and use of human tissue-based assays provides an obvious alternative to the current approaches used to predict human pharmacological responses. However, despite this, very little drug development seems to be conducted using human tissues. We know from discussions with the UK Medicines and Healthcare Products Regulatory Agency (MHRA) that some companies do use these models for supporting internal early development decision-making processes, but this is on a relatively small scale and the data are rarely included in submissions to the international regulatory agencies.

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Figure 1: The motivations behind adopting human tissue-based approaches for safety pharmacology studies.

References

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Acknowledgements

The authors would like to acknowledge the contribution made by the members of the NC3Rs and MHRA joint working group (see supplementary information for membership) for developing the survey and analysing the data, the organizations that helped to disseminate the survey, and the respondents who took the time to complete the survey.

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Authors and Affiliations

  1. National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, NW1 2BE, UK

    Anthony Holmes

  2. Stem Cells for Safer Medicines (SC4SM), London, SW1E 6QT, UK

    Frank Bonner

  3. Medicines and Healthcare products Regulatory Agency (MHRA), London, SW1W 9SZ, UK

    David Jones

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  1. Anthony Holmes
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  2. Frank Bonner
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  3. David Jones
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Corresponding author

Correspondence to Anthony Holmes.

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The authors declare no competing financial interests.

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Supplementary information

Supplementary information S1 (table)

Membership of the NC3Rs/MHRA Human Tissue for Safety Assessment Working Group (PDF 160 kb)

Supplementary information S2 (table)

NC3Rs/MHRA Questionnaire on the use of human tissue for saftety pharmacology (XLS 195 kb)

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Holmes, A., Bonner, F. & Jones, D. Assessing drug safety in human tissues — what are the barriers?. Nat Rev Drug Discov 14, 585–587 (2015). https://doi.org/10.1038/nrd4662

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