Early embryonic development, reproductive

Before administration of a NME to man, a mutagenicity test in bacterial cells (Ames test), with and without metabolic activation, and tests for chromosomal aberrations in mammalian cells should be negative. Any positive or equivocal results will require additional tests to be performed before proceeding to man. Studies of embryo-foetal toxicity should be performed before administration of a NME to women of reproductive potential. Studies of fertility, early embryonic development and pre- and post-natal development are not required at this stage of development neither are carcinogenicity studies. 

Study of Fertility and Early Embryonic Development to Implantation in Sprague-Dawley Rats (Segment 1) ICH S5A Detection of Toxicity to Reproduction for Medicinal Products and FDA 4-6 6-8 125,000-175,000... 

Figure 4 International Conference on Harmonisation guidelines on detection of toxicity to reproduction for medicinal products, (a) Study of fertility and early embryonic development (4.1.1) (b) study for effects on prenatal and postnatal development, including maternal function (4.1.2) (c) study for effects on embryo-fetal development (4.1.3) (d) single-study design (4.2) (e) two-study design (4.3).

Reproductive and developmental toxicology studies, with information on rangefinding studies and supportive TK evaluations, are to be ordered by nonpivotal studies and pivotal studies, which include fertility and early embryonic development to implantation, effects on embryo-fetal development, effects on pre- and postnatal development including maternal function. If conducted, studies in which juvenile animals are dosed and evaluated are to be included in this section. 

These tests evaluate the potential effects of medical devices, materials, and/or their extracts on reproductive function, embryonic development (teratogenicity), and prenatal and early postnatal development (Table 7). The application site of the device must be considered and tests and/or bioassays should only be conducted when the device has potential impact on the reproductive potential of the subject. 

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