Revision of the ICH guideline on detection of toxicity to reproduction for medicinal products: SWOT analysis

SWOT analysis of current ICH S5(2) on toxicity to reproduction for pharmaceuticals:•Strengths: safety record, acceptance, flexibility.•Weaknesses: alternative tests, risk assessment, limit dose, mAbs, drugs in semen.•Opportunities: 3Rs, TK, testing strategies, new technologies, maternal toxicity.•Threats: emerging science, contradiction with other guidelines, bureaucracy, etc.

SWOT analysis was used to gain insights and perspectives into the revision of the ICH S5(R2) guideline on detection of toxicity to reproduction for medicinal products. The current ICH guideline was rapidly adopted worldwide and has an excellent safety record for more than 20 years. The revised guideline should aim to further improve reproductive and developmental (DART) safety testing for new drugs. Alternative methods to animal experiments should be used whenever possible. Modern technology should be used to obtain high quality data from fewer animals. Additions to the guideline should include considerations on the following: limit dose setting, maternal toxicity, biopharmaceuticals, vaccines, testing strategies by indication, developmental immunotoxicity, and male-mediated developmental toxicity. Emerging issues, such as epigenetics and the microbiome, will most likely pose challenges to DART testing in the future. It is hoped that the new guideline will be adopted even outside the ICH regions.