**2.7 Study of reproductive function and perinatal toxicity**

These studies intend to give general information on the effects of a substance on the female/male reproductive system, such as gonadal function, estral cycle, behavior of mating, conception, childbirth and nursing. They can be carried out in one or two generations. In these studies, assessment of the growth and development of the descendant is carried out. Teratogenic potential (property of causing permanent structural and functional abnormalities during the period of embryonic development) is also evaluated, as well as any potential danger for the neonate due to exposition of the mother to a substance during pregnancy is also investigated.

Worldwide harmonized guidelines for reproductive testing have been established (ICH (1996): Detection of Toxicity to Reproduction from Medicinal Products; ICH (1996): Reproductive Toxicity: Male Fertility Studies). Generally, animal studies have been conducted in three segments: in adults, in pregnant animals, and in pregnant and lactating animals.

In the case of DNA vaccines against infectious agents, they are expected to be administered to different populations, including people at fertile ages and potentially pregnant women. Therefore, these studies are required before general application of a DNA vaccine. However, these studies may not be required prior to clinical studies in populations with lifethreatening diseases, provided appropriate measures are taken to minimize risks. Prior to use of a DNA vaccine in children or newborns, the product should be tested for safety and immunogenicity in adults, and appropriate nonclinical models, e.g. with juvenile animals, should be considered regarding toxicity and induction of immunological tolerance.
