Preclinical safety evaluation forms the critical foundation for advancing antimicrobial candidates into human trials, requiring integration of early safety thinking into compound design from discovery onwards. This section addresses the essential toxicology frameworks encompassing in vitro cytotoxicity and genotoxicity screening; GLP-compliant in vivo safety pharmacology and repeat-dose toxicity studies; and systematic determination of No Observed Adverse Effect Levels (NOAEL) to establish risk-benefit profiles. Comprehensive species selection, formulation considerations, and target-mediated off-target safety risks are integrated throughout preclinical planning. Practical strategies for de-risking unexpected toxicity and designing early complex cell-based models are examined to expedite human safety translation.
Resources
8 resourcesConsiderations for making safety part of drug design.
Highlights common toxicology risks in early antibiotic development and explores strategies to anticipate and mitigate safety-related programme failures.
Highlights regulatory pitfalls in preclinical development, emphasising the importance of integrating safety considerations early in drug design. A real-world case of unexpected toxicity is used to illustrate key lessons for developers.
Explores how preclinical toxicology can be used effectively to advance antimicrobial drug development. Drawing on regulatory expertise, it covers key toxicology considerations, common development challenges and the timing of nonclinical studies to help developers plan for progression towards clinical testing.
Provides a plan of action that can help to de-risk your Investigational New Drug (IND) application and expedite the path to gaining study clearance.
Discusses safety in early drug discovery, providing a practical guide to designing safety studies and using complex cell models in early de-risking strategies and toxicity testing.
Offers recommendations on when and how to identify and evaluate the safety of drug metabolites.
Promotes international harmonisation of nonclinical safety study requirements to support clinical trials and marketing authorisation, aiming to improve efficiency, reduce animal use, and facilitate the ethical development of new pharmaceuticals.