5F-02 - US Food and Drug Administration Approval of Biologic Use in Children and Adolescents, 1965-2023

Background: Biologics are a rapidly growing class of drugs relevant to the treatment of many pediatric conditions. However, drug development and regulatory approvals have focused primarily on adults, leading to high rates of off-label use in children. Comprehensive assessments of pediatric labeling and timelines for biologics remain limited.

Objectives: To assess approval patterns and timelines to pediatric labeling for FDA-approved biologics from 1965 through 2023.

Methods: We identified all biologics licensed by the FDA’s Center for Drug Evaluation and Research using the FDA’s Purple Book and Drugs@FDA database. Biologics with license revocation, over-the-counter status, or market discontinuation were excluded. For each biologic, we extracted information on (1) the original FDA approval date, (2) all approved indications, (3) whether any indication was approved for pediatric patients ( <18 years), and (4) the date of pediatric labeling for each pediatric-approved indication. We determined the annual proportion of approved biologic indications with pediatric labeling, and classified whether pediatric indications occurred concurrently with adult approval or through subsequent supplemental approval. The mean time to supplemental pediatric labeling was calculated overall and stratified by pediatric age groups of <2 years, 2-5 years, 6-11 years, and 12-17 years.

Results: From 1965 to 2023, the FDA approved 225 biologics, representing 481 indications. Of these, 99 (44%) biologics had at least one pediatric indication approved by 2023, accounting for 146 (30%) pediatric-approved indications. There was no significant increase in the annual proportion of biologics approved with pediatric labeling (p = 0.59). Among 146 pediatric-labeled indications, 72% (n=105) were approved initially vs. 28% (n=41) via supplements (mean delay: 7.3 years, SD 4.5). Younger ages faced longer delays: 7.3 years (SD: 4.5), 7.7 (SD: 4.9), 8.1 (SD: 5.8), and 11.5 (SD: 7.8) years for children ages 12-17, 6-11, 2-5, and <2 years, respectively.

Conclusions: A large proportion of biologics receive pediatric labeling, but many approvals occur years after initial approval. Critically, younger pediatric populations consistently faced longer approval timelines, highlighting persistent inequities. Understanding these delays and age-related differences is crucial for addressing gaps in pediatric drug development and informing regulatory strategies to improve timely access to safe and effective therapies for children.