Module 9 2021

22/03/2021

Preclinical testing of biologics - Design of toxicology package

Before any toxicology studies are initiated, the following should be known : • Relevant pharmacodynamic effects in disease models (biomarkers?) • In vitro binding affinity and pharmacology-related effects in vitro (IC50) • Target expression  In one/many organs? Normal or diseased tissue? • Comparable potency between human & the chosen toxicology species • Modelling predicts target suppression possible at intended doses • Sufficient knowledge of target and MoA to understand if species will be able to predict potential human toxicities • Is there additional risk from format  New modality? • Intended clinical regimen  Single or chronic? Route of admin?

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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Preclinical testing of biologics – Typical studies and phasing but timing is case-by-case Discovery Phase FIH-Enabling Package In cerebro/In silico/In vitro

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Pharmacology models

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4 or 13wk tox study in pharmacologically relevant species

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ADCC/CDC

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During Phase 2 26wk chronic tox Carcinogenicity Risk Assessment

Cytokine release (if required)

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During Phase 3 • Reproductive toxicology study

Tissue Cross Reactivity

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Immunotoxicity

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Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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