Module 9 2021

22/03/2021

Preclinical testing of biologics Some Key Regulatory Guidelines

• ICH S6(R1): Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (2010) • ICH S9 : Nonclinical Evaluation of Anticancer Pharmaceuticals (2009) • ICH S8 : Immunotoxicology Studies (2005)  Proposed for update • ICH M3 (R2): Non-clinical safety studies for the conduct of human clinical trials with pharmaceuticals (2009) • EMA : Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products (2018) EMEA/CHMP/SWP/28367/07 Rev. 1 • EMA : Guideline on Immunogenicity assessment of therapeutic proteins (2017) EMEA/CHMP/BMWP/14327/2006 Rev 1 • FDA : Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers (2005) • FDA : Immunogenicity Testing of Therapeutic Protein Products —Developing and

Validating Assays for Anti-Drug Antibody (2019) Preclinical testing of Biologics – March 22 nd 2021

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Preclinical 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 (2018). Safety testing of monoclonal antibodies in non- human primates: Case studies highlighting their impact on human risk assessment MABS, 10 : 1-17 • Brennan FR, Cauvin A, Tibbitts J and Wolfreys A (2014). Optimized nonclinical safety assessment strategies supporting clinical development of therapeutic monoclonal antibodies targeting inflammatory diseases. Drug Dev Res 75(3), 115-61 • Prior H, Haworth R, Labram B, Roberts R, Wolfreys A and F Sewell (2020). Justification for species selection for pharmaceutical toxicity studies. Toxicology Research 9:758-770. • Brennan FR, Dill Morton L, Spindeldreher S, Kiessling A, Allenspach R, Hey A, Muller PY, Frings, W and Sims J (2010). Safety and immunotoxicity testing of monoclonal antibodies, mAbs 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

Preclinical testing of Biologics – March 22 nd 2021

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