Oral Medicines for Children in the European Paediatric Investigation Plans

Nales, D.A.; Römkens, Erwin G. A. W.; Saint‐Raymond, Agnès; Kozarewicz, Piotr; Schobben, A. F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

doi:10.1371/journal.pone.0098348

Cited by 23 publications

(15 citation statements)

References 18 publications

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“…In a review of approved PIPs for children aged 0–11 years, 37 approved PIPs for monolithic tablets were reported . Size data were available on 24 of these tablets, where two were small (0–4 mm), 15 were medium‐sized (5–9 mm) and four were large (>10 mm).…”

Section: Discussionmentioning

confidence: 99%

“…There was little information on how age correlated to tablet size within this article although it was stated that two PIPs have been agreed with tablets from 0 to 4 mm for children aged 2–5 years. The shape of tablets in approved PIPs was reported for 21 of the 37 approved monolithic tablets, 12 were round, eight were oblong/caplet/oval and 1 was a specified other shape …”

Section: Discussionmentioning

confidence: 99%

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Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

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Objectives The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products. Methods This process used a defined search strategy of indexed publications and included methods to assess the quality of the evidence retrieved. Key findings Taste/palatability was the most extensively studied area of paediatric medicine acceptability yet standard methods or criteria that define what is classed as acceptable to children is still to be defined. There have been many reports on the acceptability of medicines to paediatric populations yet major gaps in the acceptability knowledge base exist including the shape and dimensions of tablets, minitablets and capsules swallowed whole in infants and children; size and overall volume of multiparticulates; volume of liquids completely swallowed in infants and children; duration of retention within the oral cavity, size and taste of orodispersible tablets, lozenges and chewable tablets and the number of solid units dosed at each time point. Conclusions The review highlights where further information is required to support knowledge around acceptability of age-appropriate medicines. An algorithm to aid in selection of a formulation that is likely to be acceptable based on the age range to be treated by the medicine is presented as a result of this review. IntroductionThere is much evidence to support the need for age-appropriate medicines to treat paediatric patients. Pharmaceutical products for the paediatric population have a number of considerations that may not apply to adult products. In particular, the acceptability of a product needs to be clearly defined for paediatric populations and this is currently an area of great interest.The importance and incentive to study the acceptability, including palatability, of paediatric formulations was discussed in the reflection paper [1] and endorsed in the latest European Paediatric guideline on pharmaceutical development of formulations for paediatric use.[2] Before this regulatory change, there was no requirement for medicines to be demonstrated to be acceptable to children. Guidance issued by the European Medicines Agency (EMA) in 2013 states that patient acceptability must be an integral part of paediatric formulation development and described in the paediatric investigation plan (PIP).[3] Acceptability has previously been defined as 'an overall ability of the patient and caregiver (defined as "user") to use a medicinal product as intended (or authorised)'.[4] The palatability of paediatric medicines is one of the most important formulation factors in the acceptability of liquid medicines with potential to influence adherence to therapeutic regimens and outcomes.[5] Palatability has been defined as, 'the overall appreciation of a (often oral) medicine by organoleptic properties such as vision (appearance), smell, taste, aftertaste and mouth feel (e.g. texture, cooli...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

View full text Add to dashboard Cite

show abstract

“…This can lead not only to rejection of the compound (and even therapeutic concept) under study but also, and more insidiously, to questioning of the predictive value of preclinical animal models. Further, additional requirements like the need in the EU for a (pre or postauthorisation) paediatric study, even if well-intended and of long-term benefit, have added further expense and challenges to clinical development (Arango, 2015;Eichler et al, 2013;Stoyanova-Beninska et al, 2011;Van Riet-Nales et al, 2014). This has been taking place in an unfavourable economic climate, and a legal and health service environment where patent protection is of limited duration, the clinical population to be treated will likely be more confined than in the past, and the negotiation of reimbursement with national pricing agencies is increasingly protracted.…”

Section: The Challenge Of Clinically Developing Novel Agents For Cns mentioning

confidence: 99%

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

Millan¹,

Goodwin²,

Meyer‐Lindenberg³

et al. 2015

European Neuropsychopharmacology

114

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“…Following a detailed analysis, we concluded that the PDCO evaluation had resulted in little changes to the company's proposal. Apparently, companies had been able to adequately answer the EMA questions (73). Acknowledging that industry would benefit from readily available and up-todate information on the safety of excipients in children, the EuPFI has established a freely accessible Safety and Toxicity of Excipients for Paediatrics (STEP) database (53).…”

Section: Current Experiencesmentioning

confidence: 99%

Paediatric Drug Development and Formulation Design—a European Perspective

Riet‐Nales

Kozarewicz²,

Aylward

et al. 2016

AAPS PharmSciTech

Self Cite

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Abstract.The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize Bbetter^medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the BGuideline on the Pharmaceutical Development of Medicines for Paediatric Use.^Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

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Oral Medicines for Children in the European Paediatric Investigation Plans

Cited by 23 publications

References 18 publications

Evidence of acceptability of oral paediatric medicines: a review

Evidence of acceptability of oral paediatric medicines: a review

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

Paediatric Drug Development and Formulation Design—a European Perspective

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