Europe – ICH S5 (R3) guideline on reproductive toxicology

The purpose of this document is to recommend international standards for, and promote harmonization of, the assessment of nonclinical developmental and reproductive toxicity (DART) testing required to support human clinical trials and marketing authorization for pharmaceuticals. The guideline describes potential strategies and study designs to supplement available data to identify, assess, and convey risk. General concepts and recommendations are also provided that should be considered when interpreting study data.

This is a revision of the ICH guideline “S5 Detection of Toxicity to Reproduction for Medicinal Products” that was originally published in 1993. This revision brings the guideline into alignment with other ICH guidelines, elaborates on the use of exposure margins in dose level selection, incorporates a section on risk assessment, and expands the scope to include vaccines and biopharmaceuticals. It also describes qualification of alternative assays, potential scenarios of use, and provides options for deferral of developmental toxicity studies.

To assess a human pharmaceutical’s effect on reproduction and development, there should generally be information available that addresses the potential impact of exposure to a pharmaceutical and, when appropriate, its metabolites (ICH M3 (1), ICH S6 (2)) on all stages of reproduction and development. No guideline can provide sufficient information to cover all possible cases, and flexibility in testing strategy is warranted…