Module 9 2024

03/09/2024

Key Design Aspects of the FIH-Enabling Nonclinical Toxicology Study

The Organisation for Professionals in Regulatory Affairs

Preclinical Testing of Biologicals – Sept 2024

9

Nonclinical testing of biologics

The purpose of any nonclinical toxicology package is essentially to :

• Predict potential for toxicity in humans • Identify potential organs affected • Assess whether any effects are permanent or reversible • Understand the fate of the molecule – T1/2, AUC, potential for accumulation? • Evaluate pharmacodynamic biomarkers that may be used in the clinic • Anything special to consider for the intended population – Children? Elderly? Women?

• Assess whether new drug can be used safely in clinical trials

• Support selection of a safe starting dose and maximum dose for Phase I First-In Human clinical studies, and doses for longer term clinical use

• Life-threatening/severe disease may alter the acceptability of some toxicities

• Identify safety parameters/biomarkers for clinical monitoring • e.g. altered blood pressure, liver enzymes, haematology (e.g. B cell counts) or intended changes such as increased bone mineral density (BMD)

The Organisation for Professionals in Regulatory Affairs

Preclinical Testing of Biologicals – Sept 2024

10

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