Real life juvenile toxicity case studies: the good, the bad and the ugly

Reprod Toxicol. 2008 Sep;26(1):54-5. doi: 10.1016/j.reprotox.2008.04.002. Epub 2008 Jun 2.

Abstract

With the growing experience in the conduct of juvenile toxicity studies for multiple classes of compound, the 'case-by-case' approach has become under much more pressure. Instead, a general screen or 'standard design' is now commonly expected by regulatory authorities with more routine inclusion of neurological and reproductive assessments. Minor modifications or additions can be made to the design to address specific questions according to the class of drug or intended clinical use. This drift from a 'case-by-case' approach to a 'standard design' approach is present within certain reviewing divisions of the FDA, often requesting by default a rodent and non-rodent juvenile animal study. However, juvenile animal studies should be designed thoughtfully to fulfil a purpose based on scientific rationale, with each endpoint carefully considered in terms of practicality and interpretability of data generated. Only when using the appropriate strategy and design may juvenile studies add value by (1) identifying potential safety or pharmacokinetic issues for drugs intended for paediatric use, (2) suggesting additional clinical endpoints and (3) adding new information to the product label. As the knowledge from juvenile animal studies in various species grows, a better understanding of the significance/relevance of findings will be achieved.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Laboratory
  • Child
  • Dogs
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Mice
  • Pediatrics / methods*
  • Pharmaceutical Preparations / metabolism
  • Rats
  • Research Design / legislation & jurisprudence*
  • Toxicity Tests / methods*
  • United States
  • United States Food and Drug Administration

Substances

  • Pharmaceutical Preparations