Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B): Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

Research output: Chapter in Book/Report/Conference proceedingBook chapterCommunication

Per Spindler, Herman Van Cauteren

To support approval of pharmaceuticals for long term use in humans it is required that product safety is supported by acute and chronic toxicity studies in rodents and non-rodents. The duration of acute toxicity studies (S4A) and chronic rodent studies (S4B) were harmonised between the three ICH regions in 1991; whereas the process of harmonising the duration of non-rodent studies was initiated. The US FDA originally required studies of at least 12 months duration, whereas in Japan and EU studies of 6 months duration were considered acceptable as an ICH objective. In this chapter, the background for the ICH S4B guideline regarding the duration of non-rodent repeated dose toxicity studies is explained and lessons learned are discussed. Since the guideline was issued in 1997 changes occurred in e.g. the language of the European legislation, and the requirements for non-clinical studies to support clinical development has progressed within the ICH (M3): we therefore consider options such as prospective evaluation, biomarker-based mechanistic understanding, toxicokinetics and the use of evidence-based medicine to support further joint activities to harmonise the duration of non-rodent toxicity studies at the global level.
Original languageEnglish
Title of host publicationGlobal Approach in Safety Testing: ICH Guidelines Explained : Global Approach in Safety Testing: ICH Guidelines Explained
Number of pages16
Volume1
PublisherSpringer Publishing Company
Publication date1 Feb 2013
Edition1
Pages159-174
Chapter8
ISBN (Print)1461459494
ISBN (Electronic)978-1461459491
Publication statusPublished - 1 Feb 2013
SeriesAAPS Advances in the Pharmaceutical Sciences Series (Book 5)

ID: 90204573