ABSTRACT
Juvenile toxicology is complicated due to the dynamic, anatomic, and physiological changes that occur during growth and development of an individual. Nonclinical juvenile toxicity studies are logistically complicated due to the design of the study and their size, the number, diversity, and interdependence of end points based on target organ development, the myriad modes of actions that need to be evaluated, and the constraints due to the physical size of the animal (e.g., route of administration, necropsy techniques, blood collection, behavioral) and its growth during the study. Juvenile toxicity studies aim at bridging potential data gaps (Figure 11.1) between the preand postnatal toxicity studies (Segment III) where the offspring are potentially exposed in utero and through maternal milk until weaning and the repeat-dose toxicity studies (in young adult animals). The decision on whether
studies in juvenile animals will be required will be made by the appropriate regulatory agency. The likelihood of having to perform a juvenile toxicity study can be roughly determined by several factors: age of the pediatric patient, target organs (especially developing organs) based on clinical and nonclinical study results in adults, class history of the drug, and the indication (e.g., is it life-threatening?) (Figure 11.2). There is no STANDARD juvenile toxicity study design; however, the study designs are becoming more standardized. The study design needs to consider different stages and pace of development of the organ systems at risk in human and the animal species’ equivalent. Species, age at initiation and duration of treatment, “within” versus “between” litter designs, ages at various assessments, and end points measured during and after treatment are all major considerations in designing studies on a case-by-case basis.
