What have we learned from pre-clinical juvenile toxicity studies?

Reprod Toxicol. 2009 Sep;28(2):226-9. doi: 10.1016/j.reprotox.2009.04.001. Epub 2009 Apr 10.

Abstract

Juvenile toxicity studies have assumed a higher priority within the pharmaceutical industry following recent changes in regulations. The requirement and designs of these studies should be on a 'case-by-case' basis. Discussions have suggested that recently the regulatory agencies have requested a more standard design incorporating multiple parameters, despite the disparity in the data available and the mode of action and indication of the respective drugs. In addition, the general perception was that studies were generating nothing new; there was no clear indication of novel toxicity or sensitivity; and the findings observed were predictable from what was already known. Clarity was therefore required both in terms of the study designs used and their usefulness and ability to generate meaningful data. This paper discusses the contributions from 10 pharmaceutical companies of 39 studies to clarify what has been learned and whether this has contributed to our greater understanding. Juvenile toxicity studies should be designed to fulfil a scientific rationale, only after first deciding what useful toxicological information might be obtained. Should a study be conducted, the endpoints must be assessed for both practicality and interpretability. Only when using appropriately designed studies can we adequately identify potential safety or pharmacokinetic issues, suggest additional clinical endpoints and/or contribute to the product label.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Animals, Newborn
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions*
  • Endpoint Determination
  • Pharmaceutical Preparations / metabolism
  • Predictive Value of Tests
  • Rats
  • Research Design
  • Swine
  • Swine, Miniature
  • Toxicity Tests / methods*

Substances

  • Pharmaceutical Preparations