Bridging studies in support of oral pediatric formulation development.

Adequate pediatric formulations are a must to ensure compliance to treatment, and safe delivery of the intended dose. Adult formulations may not be suitable for children, and new pediatric formulation(s) must be developed for the pediatric studies, and for market. As the development of pediatric formulations with optimized properties for market might be challenging, preliminary "enabling" formulations might be envisaged for early pediatric studies, prior to the introduction of more elegant market formulations in the confirmatory study. Supportive clinical studies, such as relative bioavailability (RBA) studies may be necessary to establish the bridge from adult and/or enabling formulations to the final pediatric formulation. Late changes to the pediatric formulation will necessitate establishment of bioequivalence (BE) between the two drug products. As failure to demonstrate BE can delay approval, it is strongly advised that the final pediatric formulation(s) be introduced no later than in the pivotal program. RBA studies assessing performance of pediatric formulations are typically performed in adult healthy volunteers, however a possible interplay between age/disease and formulation effects must be taken into account. Formulation bridging based on in vitro approaches might be envisaged under certain circumstances, such as minor formulation changes, development of new dosage strengths, or BCS class-supported biowaivers.