Bioequivalence in Children

Children are not miniature versions of adults. They are a heterogeneous group that differ developmentally, physiologically and psychologically from adults. The ongoing growth and maturation of organs affects both the disease course of asthma and the efficacy of medications. Consequently, asthma is a different disease in children than in adults and medications suitable for adults may not be successful in children.

The airway in the younger child differs from the airway in the adult and the amount of the dose of an inhaled drug reaching the lower airway in an infant and in a young child will differ from the amount which would reach the lower airway in an adult. The child displays different breathing patterns, tidal volumes, airway geometry, etc. compared with adults. Resistance and inspiratory flow differ between the older child/adolescent and the younger child.

Children often metabolize drug differently and organ sensitivity is different often with increased susceptible to the systemic adverse effects. Therefore a child may be inadequately treated and/or exposed to unwanted adverse events due to age-related differences in the drug handling or drug effects which may lead to different dose requirements to achieve efficacy or to avoid adverse effects.

Therefore it is not possible to extrapolate from the adult to the child and particularly to the younger child when comparing two inhaled products. Products may be equivalent in adults but may not be equivalent in children.Therefore, recent EU legislation reguires specific clinical trials in paediatric populations including studies on bioequivalence (Ref 1).


European Medicines Agency (EMEA)'s Committee on medicinal products for human use (CHMP) has issued guidelines on the requirements for clinical documentation for orally inhaled products (OIP). (Ref 2) This guideline recommends: "Advice from appropriate experts in the field might be useful to ensure that tests and assessments carried out are appropriate and are in line with current thinking."


A Clinical Research Center on Pediatric Asthma This Website is responding to the EMEA call for collaboration between pharma industry and the clinical researcher. We are presenting a brief summary of the pharmacology of aerosol therapy in children with an emphasis on the studies of bioequivalence of inhaled cortisosteroids. Particularly the website aims to present the state of the art methods for such studies of bioequivalence in children.
Professor Hans Bisgaard • Copenhagen • Denmark •