Pediatric formulation issues identified in Paediatric Investigation Plans

Abstract

Since the European Paediatric Regulation was introduced in 2007, companies developing new medicinal products or new indications/routes of administration/pharmaceutical forms are obliged to present age-appropriate formulations for the pediatric population within a Paediatric Investigation Plan (PIP) to the European Medicines Agency. Our review highlights a number of discrepancies between what is proposed by applicants and what is considered acceptable by regulators, taking a sample of PIP applications assessed by a specialized Formulation Working Group (FWG) of the Paediatric Committee in 2009. This Working Group assessed 43% of the total number of validated PIP applications during that year. Ninety-two percent of the formulations assessed raised at least one issue, mainly relating to excipients, appropriateness of the route of administration or pharmaceutical form, dosing accuracy and patient's acceptability. A stronger focus on all these aspects, considering the targeted age range, the severity of the disease and the treatment duration, could streamline the development process.

Keywords::

• European Medicines Agency
• excipients
• Paediatric Committee
• pediatric formulations
• Paediatric Investigation Plans
• pharmaceutical development

Disclaimer

The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.

Acknowledgements

The authors are grateful to A Saint Raymond for helpful comments on this manuscript, to the Paediatric Committee and its Formulation Working Group for the monthly review of Paediatric Investigation Plans.

Financial & competing interest disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The European Paediatric Regulation aims to promote the development of age-appropriate pediatric formulations.

• When needed, a specialized Formulation Working Group of the European Medicines Agency Paediatric Committee systematically reviews the quality part of Paediatric Investigation Plans.

• Over the year 2009, this Working Group reviewed 125 pediatric formulations proposed by companies, among which 115 were considered not adequate or not sufficiently justified for the targeted pediatric subsets.

• Concerns related to the inadequate route of administration or pharmaceutical form, safety of excipients used, dosing accuracy, minimization of medication errors, palatability and patient's acceptability.

• Oral solid flexible pharmaceutical forms offer a number of advantages and should be investigated when relevant.

• Increasing the knowledge on excipients’ exposure and safety in the pediatric population is one of the current challenges.

• Collaboration between regulatory agencies, academia and private sector is a key aspect of the success in development of age-appropriate pediatric formulations.