Written By: Hala Fadda
April 14, 2022
In the era of digital health and 3D printing for personalised medicines, there is still a scarcity of paediatric medicines all over the world. Even when age-appropriate formulations have been developed and are available on the market, they may not be accessible, especially in low- and medium-resource settings. The paediatric medicines gap has been recognised by the World Health Organization (WHO), which led to the resolution of the 69th World Health Assembly that promotes innovation and access to quality, safe and effective medicines for children.
Over half of paediatric medicines are prescribed off-label, which can lead to ineffective treatments, risk of adverse drug reactions and non-adherence. Global regulatory initiatives have made significant leaps in paediatric clinical trials to ensure safety and efficacy of paediatric prescribing. Examples of paediatric regulatory initiatives in the USA include the Food and Drug Administration Best Pharmaceuticals for Children Act and Pediatric Research Equity Act, and in the European Union the European Medicines Agency Paediatric Investigation Plan. While these initiatives have shown promise for the approval of new drugs, there continues to be a lack of attention to furthering the use of off-patent medicines. In fact, it is these existing authorised medicines or “older” medicines that predominate the WHO Essential Medicines List for Children and around half of them do not have age-appropriate formulations.
Even when age-appropriate formulations are commercially available, their cost may be extortionate for some regions, levels of certain excipients may cumulatively exceed the safety limits and dosing accuracy may be a challenge, especially for neonates and infants. Manipulation of medicines continues to take place, including crushing of tablets and mixing with water or soft food, without evidence of efficacy, bioavailability or safety. Moreover, palatability is often a barrier to adherence.
The Pediatric Formulations Focus Group (PFFG) at FIP was set up to improve availability and accessibility of age-appropriate medicines for all children around the world. PFFG’s recent study has shown that paediatric oral extemporaneous compounding continues to be an important practice in different regions of the world when commercial preparations are not available or suitable. However, important challenges to this oral compounding have been revealed, including lack of availability of raw materials, lack of validated formulations with safe excipients, limited guidelines and an unprepared workforce. We have a fragmented landscape when it comes to oral extemporaneous compounding, and disparities exist between and within countries. The goals of the PFFG are global harmonisation of practices and the identification of formulations that are robust, safe, stable, palatable and feasible, and making these publicly available. A further goal is to prepare our workforce so that they adopt best practices in oral compounding.
Where do we go from here?
As pharmacists, we need to ensure that levels of excipients are not exceeding the recommended exposure levels, especially in polypharmacy situations. Continuity of treatment in primary and secondary care is paramount, as is communication with healthcare teams to achieve appropriate prescribing and to overcome barriers to adherence.
At FIP we are working towards global and coordinated efforts into the research and development of accessible and affordable age-appropriate formulations. While liquids have traditionally been the dosage form of choice for children, evidence is now emerging that solid oral dosage forms, including multi-particulates (pellets, beads, granules) and mini-tablets (<4mm in diameter), provide acceptability, flexibility and stability. Orodispersible and chewable tablets are also showing promise provided that adequate taste masking is achieved. Children are not small adults; they span the age range of <0 days (preterm newborn infants) to 16–18 years (adolescents), therefore one size does not fit all. Dosage forms that provide multiple dose strengths and can be administered in more than one way will improve acceptability.
Children constitute approximately 30% of the world’s population and we owe it to them to continue working together to develop age-appropriate formulations.