OBJECTIVES

The development of pediatric orphan drugs in the United States (US) and the European Union (EU) are regulated simultaneously by orphan drug and pediatric drug legislation. The study aims to compare the regulatory framework for pediatric orphan drugs in both regions.

METHODS

A comprehensive literature review about orphan drug and paediatric drug legislation was conducted using the following databases: the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) websites, PubMed® database, and ad-hoc searches in grey literature.

RESULTS

The application for an orphan designation is a voluntary action in both regions; however, pediatric development for orphan drugs is optional under the Best Pharmaceuticals for Children Act in the US, yet is mandatory in the EU under the Pediatric regulation, unless a deferral or waiver is granted by the EMA. The current list of class waivers published by the EMA has been in force since 2018. Both regulators introduced incentives for pediatric orphan drug developers, such as early scientific and regulatory support, fee reduction, an additional market exclusivity period, and accelerated approval pathways. Furthermore, the Food and Drug Administration (FDA) Rare Pediatric Disease Priority Review Voucher (PRV) program, which will be cancelled in 2022, allows the FDA to award a priority review voucher for a subsequent marketing application of a pediatric orphan drug or biologic. To foster the research in pediatric orphan drugs in the US, pediatric studies will be obligatory for certain drugs and biologics with orphan designation, according to the Research to Accelerate Cures and Equity for Children Act, which will come into force on August 18, 2020.

CONCLUSIONS:

The development of pediatric orphan drugs faces enormous regulatory challenges. Both regulators have created incentives and introduced later specific obligations for the developers to foster pediatric clinical trials with orphan drugs.