Extended screening of drugs for reproductive effects to provide
data in support of Clinical Trials applications. The studies are best conducted
as an integrated sequence, appropriate for the population that is to be exposed
and designed to mimic the intended in-use situation. For women in particular,
age group and contraceptive status are taken into account in determining the
timing of studies.
Studies to International Conference on Harmonisation (ICH) Guidelines
(Topic S5A: Detection of Toxicity to Reproduction for Medicinal Products) are
accepted in all three principal marketing regions of the world (EU, Japan and
USA).
The main objectives are to assess possible impairment of embryo-fetal
development arising from direct treatment of the mother, and of effects upon
fertility if the parents are treated prior to conception. There is also the
increasingly common requirement to assess effects in juvenile animals, if the
test material is likely be used to treat children.
- Embryo-fetal development - monitoring survival, growth and physical development
of the embryo and fetus when the mother is treated from implantation to closure
of the hard palate (end of the period of ‘major’ organogenesis).
Two species (one rodent and one non-rodent, in principle) required for US
prior to inclusion of women of child bearing potential in Phase III.
- Study of fertility and early embryonic development to implantation - monitoring
gamete development, mating behaviour, fertility, implantation and embryonic
development / survival to the time of implantation. Assessment in males and
females (usually, but not essentially, in a combined study) required by the
US and EU prior to Phase III.
- Juvenile toxicity study(s) - monitoring growth and post-natal functional
development in young animals, commonly including recovery from treatment and
a test of reproductive performance. Such studies are increasingly seen as
an integral part of pre-clinical safety evaluation for drugs that are intended
for (or are very likely to be used in) the paediatric population. The studies
are designed on a case-by-case basis, to bridge data-gaps between the pre-
and post-natal study and other repeat-dose toxicity studies. Usually, only
one species is required: normally the rat (unless specifically contra-indicated).
Where a juvenile toxicity study is indicated, the pre- and post-natal study
should also be completed at this time (otherwise, this latter study is not
normally required until registration).
Together with our extensive support departments, we provide
the full comprehensive package of tests required for registration and market
authorisation, which ultimately helps speed your product to market.
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