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Updated: Jun 17, 2026

Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats
Published on: October 13, 2018
The nonclinical fertility study design for pharmaceuticals
Steven A Lerman1, Kok Wah Hew, Jane Stewart
1GlaxoSmithKline R&D, King of Prussia, Pennsylvania 19406-0939, USA. steven.2.lerman@gsk.com
Abstract:
Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document, "Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility." Studies that assess a candidate drug's effect on fertility are generally conducted in rats. The evolution of, and ultimate harmonization of, fertility study designs are reviewed, and specific elements of an acceptable design, as well as the recommendations for presentation of data, are described in detail. Additionally, the timing of nonclinical fertility studies in relation to clinical studies that enroll men and women of reproductive potential is reviewed. Possible strategies for combining fertility assessment with other study designs are also presented. This article provides testing laboratories, sponsors, and regulatory agencies with a comparison of current methods and designs, with the aim of providing a common understanding of the critical design features.
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