Module 9 2021

23/03/2021

Nonclinical Toxicology

Goal of studies • Help define safe dose of antigen/adjuvant • Identify unknown or potential adverse effects Choice of studies • In vitro and in vivo • Depends on target population (e.g. women of childbearing potential? *) • Local tolerance/ Systemic tolerability • *Developmental and Reproductive toxicity

Follow guidelines on the conduct of toxicity studies ICH- CHMP- FDA National regulations (NR) and on the nonclinical evaluation of vaccines: WHO-CHMP-FDA National regulations (NR)

Not applicable or only case to case: -safety pharmacology -Genotoxicity -Carcinogenicity

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Standard timing of nonclinical pharmacology and toxicology studies

Prior to FTIH

Prior to PH II/ III

Prior to submission



Justify antigen and adjuvant use (POC) Select and justify species for toxicity testing [Genotoxicity] Repeat dose toxicity including local and systemic tolerance. Support safe clinical dose Characterise immune response MOA of vaccine [Developmental and reproductive toxicity] [studies to confirm comparability of manufacturing or formulation changes]

[ = on case to case basis]

Note - Separate non-clinical testing of adjuvant alone is also required

FTIH = First Time In Human; POC = Proof of Concept; PH = Phase; MOA = Mode Of Action

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