In this article, Dr Simon Bryson, CEO and Co-Founder of Proveca, a company that specialises in the development and licensing of medicines for children, explains why developing better paediatric formulations is so important.
Many medicines, even essential medicines, are not licensed for paediatric use. Children differ from adults in several important aspects of pharmacotherapy and yet, for years, it has been common practice to prescribe unlicensed off-label medicines that have not been properly evaluated for children. (1)
Most medications given to children are not in age-appropriate formulations. Pharmacists, parents or caregivers often have to manipulate an adult medicine in a way that is not described in the Summary of Product Characteristics. The manipulation process can increase variability and the potential for inaccurate dosing – there may be overdosing and unintended side-effects or underdosing and a reduction in efficacy. In addition, excipients used in adult medications (e.g., propylene glycol, ethanol and sorbitol) may not be safe in children. (2) Excipients may not be metabolised or eliminated in the same way in children as in adults due to physiological or developmental differences and excipient exposure should be minimised. An additional challenge that specifically relates to the development of children’s medicines is the need for accurate dose administration for varying ages and weights, from babies to adolescents.
In addition to safety and efficacy considerations, easy-to-use, age-appropriate formulations can improve the quality of life of the child and their caregivers, particularly when the patient has a chronic condition requiring long-term treatment and polypharmacy. Palatability can be crucial to adherence and this is especially important in children due to different taste preferences.
In 2007, European Paediatric Regulation came into force to improve the health of children by increasing research, development and authorisation of medicines based on specific paediatric experience. A key part of this initiative was the introduction of Paediatric-Use Marketing Authorisation (PUMA), a dedicated licensing process. (3) PUMAs aim to stimulate research by offering 10 years of data exclusivity for the development and commercialisation of paediatric formulations of off-patent drugs.
When considering a PUMA-approved drug versus a generic medicine, the licensed product should be prescribed since this has been developed according to a paediatric investigation plan agreed by the EMA’s Paediatric Committee and they may not be interchangeable.
Regulations have resulted in some progress in the availability of paediatric formulations; however, the number of PUMAs granted is relatively small. Novel approaches to paediatric formulation development may prompt further advances. Most oral formulations for children have typically been in the form of syrups, oral solutions or suspensions to permit administration of different doses. New solid oral formulations are emerging, such as orodispersible minitablets, that may allow dosing flexibility, while reducing issues concerning harmful excipients and palatability.
Looking to the future, improving paediatric pharmacotherapy will require collaboration between industry, healthcare professionals and regulators alongside valuable input from the patients and their families. Children should not be ‘therapeutic orphans’ – they deserve the same standards as adults, with specific formulations designed to meet their needs.
- World Health Organization. 46th report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations – TRS, No. 970, Annex 5. Available at: https://www.who.int/publications/i/item/WHO_TRS_970 (accessed 4 March 2021).
- Arthur S, Burgess A. How to identify and manage ‘problem’ excipients in medicines for children. The Pharmaceutical Journal 2017;299:7903.
- European Medicines Agency. Paediatric-use marketing authorisations Available at: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/paediatric-medicines/paediatric-usemarketing-authorisations (accessed 4 March 2021).
About the Author
Dr Simon Bryson is CEO and Co-Founder of Proveca, a company that specialises in the development and licensing of medicines for children. He has a PhD in Paediatric Pharmaceutics, and advises government, industry and academia on paediatric medicine development.
UK-PRO-2021-022 WA March 2021