Weight of Evidence: Is an Animal Study Warranted? Assessments for Carcinogenicity, Drug Abuse Liability, and Pediatric Safety

Int J Toxicol. 2024 Sep-Oct;43(5):435-455. doi: 10.1177/10915818241259794. Epub 2024 Jul 20.

Abstract

Nonclinical safety studies are typically conducted to establish a toxicity profile of a new pharmaceutical in clinical development. Such a profile may encompass multiple differing types of animal studies, or not! Some types of animal studies may not be warranted for a specific program or may only require a limited evaluation if scientifically justified. The goal of this course was to provide a practical perspective on regulatory writing of a dossier(s) using the weight of evidence (WOE) approach for carcinogenicity, drug abuse liability and pediatric safety assessments. These assessments are typically done after some clinical data are available and are highly bespoke to the pharmaceutical being developed. This manuscript will discuss key data elements to consider and strategy options with some case studies and examples. Additionally, US FDA experience with dossier(s) including WOE arguments is discussed.

Keywords: carcinogenicity; drug abuse liability; juvenile toxicity; pediatric investigative plan; pediatric safety; regulations; weight of evidence.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenicity Tests
  • Carcinogens / toxicity
  • Child
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Risk Assessment
  • Substance-Related Disorders*
  • United States
  • United States Food and Drug Administration

Substances

  • Carcinogens