Proposals for model‐based paediatric medicinal development within the current European Union regulatory framework

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Abstract
WHAT IS ALREADY KNOWN ABOUT THE SUBJECT • The use of modelling and simulation (M&S) in paediatric drug development has been the subject of numerous scientific publications in the last decade. • Many scientific teams have elaborated on the methodology and provided successful examples of the added value of M&S in this area. • Furthermore, regulatory bodies and the US Food and Drug Administration in particular have provided guidance on good modelling and simulation practice and on the role of M&S in drug development. WHAT THIS STUDY ADDS • This paper attempts to position M&S in the European regulatory environment based on European Medicines Agency (EMEA) guidelines. • It presents the personal views of the authors on the issues discussed in the EMEA workshop on modelling in paediatric medicines (14–15 April 2008) 1 . • It proposes an algorithm for the practical implementation of M&S in paediatric drug development and a forum for further discussions. The new paediatric European Union (EU) regulation and the consequent demand for paediatric studies on one hand and the ethical need for minimizing the burden of studies in children on the other hand necessitate optimal techniques in the assessment of safety/efficacy and use of drugs in children. Modelling and simulation (M&S) is one way to circumvent some difficulties in developing medicinal products in children. M&S allows the quantitative use of sparse sampling, characterization and prediction of pharmacokinetics/ pharmacodynamics (PK/PD), extrapolation from adults to children, interpolation between paediatric age subsets, optimal use of scientific literature and in vitro/preclinical data. Together, industry, academia and regulators recognize the usefulness of modelling and simulation in this setting. However, even if M&S is an emerging science, its integration in the EU regulatory decision making is for the time being deficient and M&S expertise is concentrated in big pharmaceutical companies and academic institutions. The European Medicines Agency, acknowledging all the above conditions, organized and hosted a Workshop on Modelling in Paediatric Medicines. The article presents the personal views of the authors on the issues presented and discussed in the workshop. We attempt to identify the regulatory framework for the use of M&S in paediatric medicinal development and to make proposals for model-based paediatric medicinal development. The objective is to open the discussion between industry, academia, paediatricians and regulators on the optimal use of M&S in paediatric medicinal development.