Due to ethical concerns, testing medications directly on pregnant women is strictly limited. Therefore, non-clinical safety tests play a crucial role in assessing potential risks associated with a drug for pregnant women and the developing fetus. Some key non-clinical safety tests are required to support drugs intended for use in pregnant women. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has implemented the primary regulatory guidance for Design and Development Safety Pharmacology (DART) studies, particularly those involving developmental and reproductive toxicology (DART) assessments. ICH S5(R3) – Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals.
DART studies are performed to evaluate the potential effect of a given test drugs on reproductive performance of the parents and development of the offsprings. It typically includes the below studies.
| study type | Description |
| Segment I,Fertility and Embryonic Development Study | The test drug is administered to animals (rat or mice) prior to mating (28/70 days in male and 14 days in females) through mating, and implantation in rat/mice or rabbit. The purpose of this study is to quantify the effect on estrous cyclicity, spermatogenesis, and fertility of parents, development of offspring and on male reproductive organ. |
| Segment IIEmbryo-Fetal Developmental study | The test drug is administered to the animals (rats or mice or rabbit) from the day of implantation to the closure of the hard palate. This study is providing the information concerning the effects of prenatal exposure on the pregnant test animal and on the developing fetus. |
| Segment IIIPre-and Postnatal Study | The test drug is administered to animals (rat or mice) from the Gestation day 6 to Lactation day 21. The purpose of this study is to quantify the effect on late fetus development, the process of parturition, developmental (behavioural and functional) of offspring. |
| Juvenile Toxicity Study | The design of Juvenile toxicity study is based on the age of paediatric population. The selection animal species, dose, dose duration and selection of appropriate endpoints are depending up on the targeted paediatric population. The juvenile toxicity study is required when human safety data and previous animal studies are insufficient for a safety evaluation in the intended paediatric age group or it should be performed on a case-by-case basis. |