Assessing the Appropriateness of Formulations on the WHO Model List of Essential Medicines for Children: Development of a Paediatric Quality Target Product Profile Tool

Abstract

The World Health Organization’s Model List of Essential Medicines for Children (EMLc) presents a list of the most efficacious, safe, and cost-effective medicines for priority conditions, intended for use in children up to 12 years of age. However, gaps in global availability and use of age-appropriate formulations of medicines for children still exist. To address these shortcomings, a comprehensive analysis of the appropriateness of formulations of essential medicines for children is being undertaken through the Global Accelerator for Paediatric Formulations (GAP-f) network, a WHO network launched in 2020 to respond to the paediatric treatment gap. This article describes the development and application of a paediatric Quality Target Product Profile (pQTPP) tool by WHO, to retrospectively evaluate the paediatric age-appropriateness of formulations on the EMLc and identify potential formulation gaps, to inform the review of the EMLc in 2023. A combination of paediatric-centric and global health-focused attributes and targets were defined, taking into consideration regulatory agency paediatric development guidelines and literature sources, and a qualitative scoring system was developed and tested. Example evaluations of paracetamol and clofazimine are provided, illustrating the tool’s use. The assessment of EMLc formulations is ongoing and shortcomings and gaps in EMLc formulations have already been identified. The pQTTP tool may also be applied to national lists and prospectively when designing new paediatric formulations.

Orally Dispersible Dosage Forms for Paediatric Use: Current Knowledge and Development of Nanostructure-Based Formulations

“…Moreover, compared to a classic QTPP, it includes characteristics that have a higher impact on the paediatric patient and the efficacy and safety of their treatment, such as palatability. Walsh et al have developed a model pQTPP, along with a risk score-based tool previously conceptualised by the WHO, to identify whether the medicines in the pre-development or development phase, as well as the already existing products containing APIs included in the Model List of Essential Medicines for Children, are fit for paediatric pharmacotherapy [77].…”

Extemporaneously compounded liquid formulations of clofazimine

“…4 Walsh et al also identified a major gap to dose young children and confirmed by clinicians’ experience, given the difficulty in manipulating the contents of the capsule. 5 There is also a need for alternative formulations that meet the needs of patients with dysphagia or those who are intubated.…”

Development and evaluation of an assessment of the age-appropriateness/inappropriateness of formulations used in children

“…The tool uses reports of direct observation of attempted/successful administration to confirm and thus expand upon the ages of children and reasons why a medicine may either be classified as AaF or AiF [ 23 , 27 – 29 ]. The classification ‘Maybe age-appropriate’ indicates that the DF was either authorised but used OL or was an UL medicine.…”

“…Other studies have reported assessment of AaFs [ 22 , 23 , 38 , 45 , 46 ] by screening lists of medicinal products according to set criteria or making assumptions for the expected ‘user’; in terms of generic age/weight band profiles and the anticipated physical capability of a child, consistent with paediatric developmental milestones. One such assumption is that children under 6 years are unable to swallow SODFs such as tablets, which is not the case [ 47 ].…”