Pediatric Developmental Safety Assessment and New Approach Methodologies: US FDA/Triangle CERSI Workshop Report

Pediatric developmental safety assessment presents distinct challenges in drug development. Children undergo dynamic changes in organ systems and drug disposition pathways during development, and drug‐related effects may be delayed or manifested differently than in adults. Pharmacovigilance data, primarily from adults, is not always predictive of the response in children. Historically, juvenile animal studies have been used for nonclinical pediatric drug safety assessments exclusively, but the reduction in animal testing is a goal of public health agencies. To address this concern, the Office of Clinical Pharmacology at the U.S. FDA and the Triangle CERSI (Center of Excellence in Regulatory Science and Innovation) convened a workshop entitled: “Pediatric Developmental Safety Assessment and New Approach Methodologies (NAMs),” attended by experts from regulatory agencies, academia, and industry. Discussions focused on three overarching topics: (i) Secondary Pharmacology Screening Tools for Assessing Pediatric Developmental Safety; (ii) Non‐clinical Tools for Pediatric Developmental Safety Assessment; and (iii) Computational and Data‐Driven Tools for Pediatric Developmental Safety. These topics were examined within the framework of the S11 Nonclinical Safety Testing In Support of Development of Pediatric Pharmaceuticals and E11A Pediatric Extrapolation guidances, which promote structured, question‐based pediatric extrapolation in drug development and authorization. The workshop concluded that NAMs hold considerable promise to advance the assessment of pediatric drug developmental safety.