The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain

• Published in: Regulatory toxicology and pharmacology 2023-02, Vol.138, p.105339, Article 105339
• Main Authors: Prior, Helen, Andrews, Laura, Cauvin, Annick, Chien, Hsiaotzu, Clarke, David O., Datta, Kaushik, Dempster, Maggie, Dybdal, Noel, Freebern, Wendy, de Haan, Lolke, Herzyk, Danuta, Hey, Adam, Kissner, Thomas, Kronenberg, Sven, Leach, Michael W., Lee, Donna, Reid, Kirsty, Schutte, Katrin, Sewell, Fiona, Trouba, Kevin, Ulrich, Peter, van Aerts, Leon, van Meer, Peter, Weir, Lucinda
• Format: Article
• Language: English
• Subjects: 3Rs; Animals; Antibodies, Monoclonal - adverse effects; Control Groups; Drug Development; Drug Evaluation, Preclinical; Humans; ICH S6(R1); Monoclonal antibody; Non-rodent; Recovery; Research Design; Reversibility; Rodent; Safety assessment; Toxicology
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2023.105339

Assessment of reversibility from nonclinical toxicity findings in animals with potential adverse clinical impact is required during pharmaceutical development, but there is flexibility around how and when this is performed and if recovery animals are necessary. For monoclonal antibodies (mAbs) and in accordance with ICH S6(R1) if inclusion of recovery animals is warranted, this need only occur in one study. Data on study designs for first-in-human (FIH)-enabling and later-development toxicity studies were shared from a recent collaboration between the NC3Rs, EPAA, Netherlands Medicines Evaluation Board (MEB) and 14 pharmaceutical companies. This enabled a review of practices on recovery animal use during mAb development and identification of opportunities to reduce research animal use. Recovery animals were included in 68% of FIH-enabling and 69% of later-development studies, often in multiple studies in the same program. Recovery groups were commonly in control plus one test article-dosed group or in all dose groups (45% of studies, each design). Based on the shared data review and conclusions, limiting inclusion of recovery to a single nonclinical toxicology study and species, study design optimisation and use of existing knowledge instead of additional recovery groups provide opportunities to further reduce animal use within mAb development programs. •A working group reviewed practices on recovery animal use during mAb development.•Data from toxicity studies (conducted 2015–2019) for 51 mAbs was shared.•Recovery animals were often included in multiple studies in the same program.•Recovery groups were commonly in control +1 mAb dose level or in all dose groups.•Opportunities to reduce animal use within mAb development programs were identified.