Age-Appropriateness of Oral Formulations Authorized for Pediatrics

Abstract Purpose Pediatric global regulatory initiatives have come into place to address gaps in evidence-based medicine for children. Objective of this study was to assess age-appropriateness of oral pediatric formulations authorized through the U.S. Food and Drug Administration’s Pediatric Rule, Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. Methods Formulation age-appropriateness was assessed using an adapted version of the World Health Organization pediatric quality product profile assessment tool. Evaluations encompassed four product attributes across pediatric subgroups: dose and dose flexibility, patient acceptability, excipient safety and administration considerations. Each attribute was scored on a three-point scale: 1 indicating high risk, 2 moderate risk, and 3 low risk. Results 214 oral formulations were evaluated. Age-appropriateness remains a concern; with less than one third of authorized oral formulations for neonates meeting criteria for age-appropriateness, in comparison to 66% for older pediatric populations. Tablets and capsules constitute 58% of formulations indicated for pediatrics, despite tablet sizes often being unsuitable for younger children. Liquid formulations for neonates present a significant oversight, as they frequently contain excipients of potential concern. As children age, swallowability of the dosage form appears to be deprioritized, with only 37% of unswallowable large size tablets for school-aged children, available in alternative dosage forms such as granules, or solids for dispersions. Conclusions Significant formulation gaps persist in pediatric medicine, with acceptability and excipient safety presenting highest risk. The potential of non-conventional solid dosage forms remains underutilized, underscoring the need for regulatory frameworks to support development of pediatric medicines.