From paediatric formulations development to access: Advances made and remaining challenges

Abstract

Developing suitable paediatric formulations and ensuring access to them by the greatest number of the 2.2 billion children worldwide are equally important to provide optimal pharmacotherapy. This review focuses on the progress made over the last two decades with paediatric oral formulations with respect to evidence for acceptability and dosing flexibility of liquid and solid oral dosage forms. It also discusses the clinical needs for, and the access to, paediatric formulations for existing authorised medicines. A significant body of new knowledge now supports the acceptability of solid oral dosage forms in children, resulting in an increasing number of medicines commercialised as multiparticulates, including minitablets that are starting to be brought to market. However, there are gaps with these formulations that deserve more research. Even though efforts have been made to identify medicines in need of age-appropriate formulations, there is no common priority list shared internationally. Such prioritisation would help to develop paediatric formulations with the greatest potential for providing a health benefit to children worldwide. In addition, available data highlight that paediatric formulation access is fragmented and unequal, with commercialisation of suitable paediatric formulations too often limited to some countries/regions. We propose actions to better align decisions during the development of paediatric formulations and promote a more globalised approach to facilitate registration pathways between different jurisdictions. Furthermore, discussions about alignment between approval, pricing and reimbursement processes should also happen, leaving working in siloes behind us. It is time for adults to start thinking outside the box for children.

Improving Pharmacist-Led Pediatric Patient Education on Oral Chemotherapy at Home

“…However, most medications for children are used off-label and may not have age-appropriate formulations to accommodate their needs [12,14]. Extemporaneous compounding of medications may be restricted by lack of information on stability, storage conditions, impact on drug absorption and bioavailability, drug efficacy, and palatability [15,16]. These challenges further complicate the pharmaceutical care provided to children and increase the risk of medication errors due to possible miscalculations, incorrect dilutions and measurements, and the use of inappropriate ingredients [17,18].…”

Taste-masking methods in multiparticulate dosage forms with a focus on poorly soluble drugs

“…Several studies have highlighted the difficulty of obtaining an accurate dose from manipulated tablets, with large dose variations and discrepancies between manipulations due to galenics, prescribed dose, or manipulator experience (3)(4)(5). Therefore, these practises cannot be considered equivalent to commercial forms manufactured according to good manufacturing practises (6,7). The consequences of using compounding/manipulation of conventional drugs approved for adults can translate into suboptimal adherence due to bad taste, underdosing with therapeutic failure, or overdosing with adverse effects (8)(9)(10).…”

“…Three main objectives were defined in this report: to promote research and development of pharmaceutical formulations for children; to ensure that paediatric pharmaceutical formulations are designed and approved for their use in the near future; to increase the availability of information on this topic by encouraging stakeholders cooperate with each other and share new information (15). There are already some excellent reviews that address the progress and challenges of paediatric formulation development (7,(16)(17)(18).…”

Paediatric and obstetrical pharmacology – Pushing the frontier forward

“…Taking medications implies that they are in a formulation that can in fact be taken. Emphasizing that children are not small adults, the need for child‐friendly formulations and the processes by which they may be developed are described in paired work by Juárez‐Hernández, Litalien and colleagues 13,14 …”

“…Emphasizing that children are not small adults, the need for child-friendly formulations and the processes by which they may be developed are described in paired work by Juárez-Hernández, Litalien and colleagues. 13,14 This themed issue covers a number of key issues in pharmacology and therapeutics for children that demonstrate that there has been tremendous progress over the past two decades in understanding the biology of drug disposition and effects in children, that this progress has been driven by legislative and regulatory changes supported by research funding, and that this understanding has in turn provided clinicians with better approaches and more tools for safe and effective drug therapy. While much has been done, much remains to be done (e.g., available funding for research in drugs for children or pregnant women is but a fraction of that dedicated to researching drugs for non-pregnant adults), notably as biologic and genetic therapies enter the clinical realm.…”