Background: The paucity of marketed drug products that have been adequately studied in infants and
children and subsequently, licensed (or labeled) for pediatric use has caused abundant use of off-label and unauthorized products in this
patient population. In those instances where insufficient pharmacologic or therapeutic information exists for children, the potential for
off-label use of medicines to result in therapeutic misadventure does as well. In the USA, a series of regulatory measures have been introduced
since 1997 which have increased both the number and scope of pediatric drug trials and also, fostered the development of ageappropriate
drug formulations by pharmaceutical companies. Provisions of these regulations for previously marketed drugs include the
potential for a company to be granted 6 months of marketing exclusivity, thereby providing them with a financial incentive. For new
drugs being developed that have potential pediatric use, the regulations mandate the inclusion of children in the drug development process.
In the EU comparable measures have been very recently (Jan 2007) signed into European law to overcome the therapeutic orphan
status of the infants and children of Europe.
Method: The aims of this study was to compare the availability of age-appropriate oral formulations labeled for use in children less than
12 years of age in Serbia, Germany and USA in 2007, and to investigate if certain drug groups of therapeutic importance to children had
fewer medicines appropriately labeled for pediatric patients available. The primary sources of information for determining the ageappropriate
oral dosage forms, and their licensing and labeling status were the official manuals on drug information and national formularies
Finding: The general availability of oral drugs was the highest in the USA (304), followed by Germany (235) and Serbia (156). From all
these oral drugs the availability of labeled age-appropriate pediatric dosage formulations was only between 21.2% and 47.7%. Moreover,
there were striking differences between the three countries in the availability of labeled age-appropriate formulations for certain drug
groups such as cardiovascular (absent in Serbia) and antiparasitic drugs (absent in Serbia and Germany).
Interpretation: Our data suggest that significant country-to-country differences continue to exist in both the number and type of oral drug
formulations that have pediatric labeling. Potential contributing factors include country-specific differences in the drug regulatory process,
capacity for pharmaceutical development and the regulatory lag time associated with the implementation of drug regulation specifically
addressing pediatric product development and labeling. We hypothesize that the new European regulation concerning medicines and
children will improve the current unacceptable situation.