Module 9 2024

03/09/2024

Nonclinical testing of biologics Some Recommended References

• Brennan FR, Cavagnaro J, McKeever K, Ryan PC, Schutten M, Vahle J, Weinbauer GF, Marrer-Berger E and Black LE. Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on human risk assessment MABS (2018) 10 : 1-17 • Brennan FR, Cauvin A, Tibbitts J and Wolfreys A. Optimized nonclinical safety assessment strategies supporting clinical development of therapeutic monoclonal antibodies targeting inflammatory diseases. Drug Dev Res (2014) 75(3), 115-61 • Brennan, F.R., Kiessling, A., In vitro assays supporting the safety assessment of immunomodulatory monoclonal antibodies, Toxicology in Vitro (2017), http://dx.doi.org/10.1016/j.tiv.2017.02.025 • Prior H, Haworth R, Labram B, Roberts R, Wolfreys A and F Sewell. Justification for species selection for pharmaceutical toxicity studies. Toxicology Research (2020) 9:758-770. • Brennan FR, Dill Morton L, Spindeldreher S, Kiessling A, Allenspach R, Hey A, Muller PY, Frings, W and Sims J. Safety and immunotoxicity testing of monoclonal antibodies, mAbs (2010) 2:3, 1-23 • Muller PY, Milton M, Lloyd P, Sims J and Brennan FR (2009). The Minimum Anticipated Biological Effect Level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies. Curr Opin Biotechnol (2009) 20:1-8

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Nonclinical testing of “other biotherapeutics” Some Useful References for gene and cell therapies • ICH Guideline S12 : Nonclinical biodistribution considerations for gene therapy products (2023). www.ich.org/page/safety-guidelines • Bolt MW, Whiteley LO, Lynch JL et al. Nonclinical Studies that Support Viral Vector-Delivered Gene Therapies: An EFPIA Gene Therapy Working Group Perspective. Mol Ther Methods Clin Dev (2020). 19:89-98 • Gallagher T. Meeting Summary : ESGCT 2022 AAV Safety Plenary Session. Human Gene Therapy (2022). 33:1217-1220 • Guidance for Industry (FDA) : Preclinical Assessment of Investigational Cellular and Gene Therapy Products (2013) • Hutt JA, Assaf BT, Bolon B, Cavagnaro J et al. Scientific and Regulatory Policy Committee Points to Consider: Nonclinical Research and Development of In Vivo Gene Therapy Products, Emphasizing Adeno-Associated Virus Vectors. Tox Path (2022). 50(1):118-146 • Moffit JS, Blanset DL, Lynch JL et al. Regulatory consideration for the nonclinical safety assessment of gene therapies. Human Gene Therapy (2022). DOI: 10.1089/hum.2022.090

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