Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Comparison of the Pediatric Drug Legislation between US and EU Food and Drug Administration Safety and Innovation Act (Title V) versus EU Paediatric Regulation (EC) No 1901/2006 ***

Julia Gröger (Abschlußjahr: 2014)

Summary
Language: English
The main goals of the pediatric drug legislations are the same in US and EU. These are improvement of pediatric drug research and increasing the numbers of ethical and scientifically valid pediatric clinical studies in order to receive safety and efficacy data to provide adequate information for the product labeling for improved pediatric care. Additionally both legislations have the goal to integrate the pediatric drug development into the standard development. These goals have been reached in many therapeutic areas nevertheless some areas like therapeutics for neonates and infants as well as therapeutics for rare diseases and long-term studies are still neglected. The US and EU pediatric drug legislations have built a complex framework for pediatric drug development. Many regulatory documents are available to assist in specific scientific and procedural questions and to guide pharmaceutical companies through specific procedures. However, for a global pediatric development approach the assistance through these documents is limited due to significant differences in regard to the regulatory requirements and expectations. The most important differences are regarding the legal scope. The Pediatric Research Equity Act requires studies for drug under review and proposed adult indication whereas the EU pediatric regulation requires studies on all pediatric indications and conditions for which the medicinal product may be useful. Different medicinal product groups are covered by the scope of the legislations. Whereas orphan drugs are not covered by the US pediatric legislation but by the EU the reverse is true for biosimilars. Further important differences are in timing of the pediatric development plan submission and the timing and consequences of the corresponding compliance check. Since the compliance check is not a pre-requisite for the validation of a NDA/BLA in the US the medicinal products can be earlier available in the US than in the EU at least for the adult population. Also new orphan drugs are earlier available in the US than in the EU for the adult population, since pediatric studies are not required under PREA for orphan drugs.
Nowadays the pediatric drug development respectively the pediatric clinical trials are globally aligned. Firstly so the number of participants is easily and efficiently reached and secondly in order to fulfill the clinical demands for the future worldwide Marketing Authorizations. Therefore all stakeholders are facing the next hurdle “Era of Global Pediatric drug development” and how the global trial development can be optimized. Already in 2007 the FDA and EMA established a collaboration program for sharing information and discussing pediatric product development plans on a monthly basis in an effort to understand and reduce differences. Also the establishment of the Parallel Scientific Advice procedure for the exchange of different views on scientific issues between EMA and FDA is a welcomed option in order to get an understanding for the specific US and EU expectations already early in the product development phase.
In conclusion the harmonization of the regulatory framework for pediatric drug development can be reached through continuous refinement and harmonization of international standards and guidelines together with the establishment of a global pediatric research infrastructure through internalization of clinical research institutions and networks. The example of the recently published manuscript “Steps towards Harmonization for Clinical Development of Medicines in Pediatric Ulcerative Colitis - a Global Scientific Discussion Part 1: Efficacy Endpoints and Disease Outcome Assessments and Part 2: Data Extrapolation, Trial Design, and Pharmacokinetics” of the International Pediatric Inflammatory Bowel Disease Working Group considered possible approaches toward harmonized drug development. In order to receive meaningful information from pediatric studies and to decrease the regulatory burden the harmonization of the PSP and PIP template or the establishment of a common core document combined with a harmonized process for interactions with FDA and EMA could be an option which should be followed up in the future. Ethical and practical considerations in conducting pediatric research should be the basis for establishment of a harmonized standard since "children are the world´s most valuable resource and its best hope for the future" (J. F. Kennedy).
Pages: 67, Annexes: pages : 11