The need for juvenile animal studies--a critical review.

Abstract With the introduction of specific pediatric legislation in the United States (US) and the European Union (EU) requiring the development of medicines for children the interest in juvenile animal studies (JAS) increased, but also the discussion about the value and necessity of such studies. Regulatory guidance regarding JAS is available from The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) M3(R2) guideline and from more specific guidance documents issued by the Food and Drug Administration (FDA) as well as the European Medicines Agency (EMA). This paper summarizes and discusses the regulatory requirements regarding the need for JAS, their design and timing as well as the current experience with such studies. The relevant guidance documents as well as several authors support a case-by-case approach regarding the need for and design of JAS. JAS should be considered, especially in cases when organ systems undergoing postnatal development, like the kidney, the skeleton or the central nervous system (CNS), have been identified as toxicity target organs, as developing organ systems usually are more sensitive to toxicity than mature organs. The relevance of the findings from JAS for human use will essentially depend on an appropriate study design, especially on the choice of species as well as the age of the juvenile animal at the start of study. As the available data from JAS show, the design of JAS seems to have improved since the introduction of specific guidance documents. However, so far, there is not enough experience to finally answer the question if JAS are useful. Interpretation of the results from JAS and their extrapolation to the pediatric population is hampered by the incomplete understanding of the animal models used in these studies as well as the lack of access to existing JAS data. Further data will be necessary to ultimately clarify the need for such studies.