Module 9 2021

22/03/2021

Preclinical testing of biologics - Justification of relevant animal species

• Toxicology studies should be performed in 2 species by default (one rodent, one non-rodent) • However NBE toxicity studies should only be conducted in the species in which it is pharmacologically active : • For mAbs and derivatives, this is often ONLY the primate • If rodent is pharmacologically relevant (i.e. NBE binds rodent target and downstream pharmacology is similar), then rodent tox studies required • Typically, FIH-enabling tox studies conducted in both species then justify use of most sensitive or appropriate species only for long-term studies • Immunogenicity of NBEs in rodents often prevents use in chronic studies • If no relevant species, consider alternative models e.g. surrogate NBE in mice or use of transgenic mice

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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Prior H et al (2020). Justification for species selection for pharmaceutical toxicity studies. Tox Res. 9:758-770.

Preclinical testing of biologics - Justification of relevant animal species

Requirements to define a species as pharmacologically relevant : • Pharmacodynamic effects seen in disease models in relevant species • In vitro binding affinity, receptor occupancy and/or pharmacological effects in animal cells • Minor change in potency of NBE against human target and animal target • Ideally <10-fold difference in affinity/relative potency • Sufficient knowledge of MoA to understand if species will predict potential human toxicities • TGN1412  Relative potency differed between humans & primates Primate immune pathway was significantly different from human

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

10

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