Evidence Gaps Continue to Shape Biosimilar Adoption in Pediatric Care

Lack of data in certain populations rather than cost impact was identified as the key factor shaping whether children received biosimilars, according to a scoping review that examined why pediatric uptake has lagged behind adult use despite expanding biosimilar availability.¹ The review mapped clinical, regulatory, operational, and ethical considerations influencing institutional decision-making around biosimilar adoption in pediatric care settings.

Explore the critical gaps in biosimilar adoption for pediatric patients, focusing on safety, regulatory challenges, and the need for more robust data. | Image credit: zinkevych - stock.adobe.com

The report, published in Pharmaceutical Medicine, was created to address a persistent gap. Although biologic medicines have transformed outcomes for children with complex and chronic diseases, biosimilars have been adopted far more slowly in pediatric populations than in adults. Prior utilization data showed that children younger than 18 years were significantly less likely to initiate a biosimilar than older adults, even as overall US biosimilar use rose to more than one-quarter of biologic initiations by 2022.² The authors aimed to synthesize published and grey literature to identify recurring themes relevant to pediatric institutions and to inform an evidence- and values-based framework for biosimilar adoption.¹

Using a PRISMA-ScR–aligned scoping review methodology, investigators searched OVID Medline, Embase, and International Pharmaceutical Abstracts from inception through September 20, 2024, and supplemented results with regulatory, health technology assessment, and professional society documents. Thirty-five articles met inclusion criteria, including prospective and retrospective cohort studies, surveys, qualitative studies, reviews, and commentaries. Twenty-six articles were pediatric-specific, while the remainder addressed broader biosimilar principles applicable to children.

Findings were organized into 14 themes across 2 overarching categories: substantive principles, which addressed what evidence and values matter, and procedural principles, which focused on how institutions operationalize biosimilar use. Substantive principles included clinical trial evidence, real-world experience, regulatory approval, cost and affordability, supply availability, suitability of dosage forms, societal values, and health risks. Procedural principles encompassed stakeholder governance, interchangeability and switching practices, inventory management, electronic prescribing infrastructure, education, and follow-up and monitoring.

Limited pediatric-specific clinical trial data emerged as a central barrier. While randomized controlled trials in adults consistently demonstrated comparable pharmacokinetics, efficacy, safety, and immunogenicity between biosimilars and reference products, most biosimilars entered the pediatric market without dedicated pediatric trials. Regulatory approvals frequently relied on extrapolation from adult data, an approach that raised concerns because developmental differences can affect drug disposition and response in children. The review highlighted particular uncertainty for pediatric conditions without adult equivalents and for children with severe or early-onset disease.

Real-world evidence partially mitigated these concerns but remained limited in scope. Observational pediatric studies, largely from Europe and focused on single switches from reference products, generally reported maintained disease control and no new safety signals. However, sample sizes were small, follow-up was short, and some cohorts reported that up to one-quarter of patients switched back to the reference product or another biologic due to reduced effectiveness, injection discomfort, or perceived adverse effects.

Cost considerations strongly influenced institutional decisions, with biosimilars typically priced at 60% to 85% of reference biologics. Pediatric studies in inflammatory bowel disease and hematology settings suggested savings of approximately 10% to 30% after switching. The review emphasized, however, that direct drug savings must be weighed against indirect implementation costs, including staff time for education, changes to infusion or delivery systems, and additional monitoring. Equity issues related to variable outpatient insurance coverage were also noted.

Patient- and caregiver-centered factors featured prominently. Surveys and qualitative studies showed that many families had limited baseline knowledge of biosimilars and expressed anxiety about non-medical switching. Trust in clinicians and clear communication were critical to acceptance, and the review identified the potential for nocebo effects when expectations were negative. At the same time, some families expressed willingness to accept biosimilars to support broader health-system sustainability.

On the procedural side, the authors found wide variation in institutional approaches to interchangeability and substitution. Most pediatric settings avoided automatic pharmacist substitution and favored physician-led switching, particularly for children who were stable on reference biologics. Multidisciplinary governance, clear electronic prescribing differentiation between products, and robust pharmacovigilance systems were consistently recommended to ensure traceability and safety monitoring.

The review acknowledged several limitations. As a scoping review, it did not formally assess study quality or quantify effect sizes. The pediatric evidence base was heterogeneous, with many studies underpowered to detect rare safety events or small differences in effectiveness. Much of the real-world data originated outside the US, potentially limiting generalizability. In addition, perspectives from industry and payers were excluded, which may have omitted insights into market-level dynamics.

The report concluded that pediatric biosimilar adoption was constrained less by a single barrier than by intersecting evidence gaps, regulatory inconsistencies, and implementation challenges. The authors called for earlier and more robust pediatric studies during biosimilar development, sustained investment in pharmacovigilance and registries, and institution-specific frameworks that balance affordability with safety and trust for children and their caregivers.

References

1. Lau E, Koo A, Kang HB, Ames M, Matinnia C, Denburg A. Considerations for biosimilar adoption in pediatrics: a scoping review. Pharmaceut Med. Published online December 1, 2025. December 22, 2025. doi:10.1007/s40290-025-00593-8

2. Hong D, Kesselheim AS, Sarpatwari A, Rome BN. Biosimilar uptake in the U.S.: patient and prescriber factors. Health Aff. 2024;43(8):1159-1164. doi:10.1377/hlthaff.2023.01215