Abstract
In the past, dosage regimens authorized for adults were extrapolated to children relying
mainly on empirical dosage adjustments. However, children are not small adults, but
a distinct and heterogeneous group in terms of physiology, disease occurrence, pharmacokinetics,
pharmacodynamics and also psychological, cognitive, and behavioral aspects. Even though
it would be helpful to know the physiological changes and the special drug treatment
needs in children, this task could not be performed due to ethical reasons. Important
issues to consider for the development of paediatric drug products refer to the administration
of the accurate dose, the use of the appropriate excipients, and acceptability. The
latter is crucial and taste-screening methods (like electronic tongues) have been
developed. A new era in paediatric medicines started with the entry into force of
paediatric regulations. In the early ‘80s, the FDA started the set-up of a regulatory
framework by authorizing issues like the Paediatric Rule, the Best Pharmaceuticals
for Children Act, the Paediatric Research Equity Act, and the Food and Drug Administration
Safety and Innovation Act. Similar efforts have been made in the EU, mainly through
the entry into force of the Paediatric Regulation and the establishment of the Paediatric
Committee, the Paediatric Investigation Plan, the Paediatric Use Marketing Authorization,
and the European Paediatric Research Network. Other efforts to bridge the gap, between
knowledge in adults and the children’s special requirements, include the extrapolation
concept of safety/efficacy aspects, the application of modeling/simulation approaches
in paediatric drug development, and the development of a paediatric Biopharmaceutics
Classification Scheme.
Key words
Paediatric medicines - Paediatric regulatory framework - Extrapolation concept
