Pediatric development is now mandated for all new medicines that do not have a class waiver or orphan disease designation in the US. Comparable, if not more rigorous, pediatric requirements are also in effect in the EU regardless of orphan disease status. From the Best Pharmaceutical for Children Act (BPCA), to the Pediatric Research Equity Act (PREA) and the Food and Drug Administration Safety and Innovation Act (FDASIA) in the U.S. to the Pediatric Regulation of 2006 in Europe--drug developers face increasing requirements to develop high-quality, age appropriate medicines for pediatrics.
These regulations were implemented to address the growing concern that the vast majority of drugs (>70% for children and >90% for neonates) were historically being prescribed off-label and in many cases had not been formally evaluated for safety and efficacy in children. This problem was also exacerbated by the fact that drugs designed for adults often required ad hoc extemporaneous formulation e.g. by crushing tablets and introducing the divided dose into food substances like apple sauce.
The pediatric regulations that are now in place in the U.S. and EU were introduced to a) reduce the off-label use of drugs in children, b) provide a structure for the proper evaluation of the safety and efficacy of a drug in pediatric patients, and c) promote the development and availability of age appropriate formulations for children.
One of the major challenges in conducting clinical trials in children, especially in rare and orphan diseases, is the limited availability of patients and reluctance of many parents and caregivers to enroll their child in a trial with an experimental therapy. Realizing these challenges and looking for innovative ways to minimize the number of children that need to participate in a clinical trial, the FDA and EMA have established the concept of pediatric extrapolation to facilitate the extrapolation of adult efficacy data to children, provided that certain conditions can be met.