In the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products. We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children. In the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US. No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children. If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered. Our data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

The paucity of evidence-based data on formulation characteristics preferred by the children is known to limit the design of tailored paediatric dosage forms. The European Paediatric Translational Research Infrastructure (EPTRI) commissioned a study to evaluate children’s dosage forms perceived preferences in some European countries and explore the feasibility of using the young persons advisory groups (YPAGs) to involve children in formulation research. An online, age-adapted survey was developed and translated into six languages. The survey link was disseminated across seven European countries: Albania, Italy, the Netherlands, and Dutch-speaking part of Belgium, Romania, Spain, and the United Kingdom. Respondents’ (n = 1172) perceived preferences for oral dosage forms primarily differed based on age, health status, and experience. Conventional dosage forms, i.e., liquid (35%), tablets (19%), and capsules (14%), were the most selected. Liquid was widely selected by children less than 12 years and by those healthy and taking medicines rarely. Monolithic solid forms were mostly chosen by adolescents and by children with a chronic disease taking medicines frequently. There was a clear lack of familiarity with more novel dosage forms (e.g., orodispersible films and granules). Noteworthy, granules were not appreciated, particularly by adolescents (52.8%). To rationalise the creation of paediatric formulations, it is important to involve children as active stakeholders and to apply tools assessing children’s perspectives on medicines to inform acceptable dosage form development from the start.

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations. Contrary to current perceptions of limited market potential, the global pediatric healthcare market is expected to generate around USD 15,984 million by 2025. There are 1.8 billion young people in the world today; 40% of the global population is under 24, creating significant future healthcare market opportunities. This review highlights a number of technology areas that have led to successful pediatric MD, including 3D printing, advanced materials, drug delivery, and diagnostic imaging. To ensure the targeted development of MD for CYP, collaboration across multiple professional disciplines is required, facilitated by a platform to foster collaboration and drive innovation. The European Pediatric Translational Research Infrastructure (EPTRI) will be established as the European platform to support collaboration, including the life sciences industrial sector, to identify unmet needs in child health and support the development, adoption, and commercialization of pediatric MDs.

The number of paediatric clinical trials in EU has remarkably increased in the last decade in response to the implementation of the new Paediatric Regulation and incentives aiming to define the need of child-specific drug development. Nevertheless, the gap between the number of paediatric and adult-randomised controlled trials is still substantial in almost every major clinical specialty. Economic, ethical, technological, geographical and cultural factors can influence the paediatric drug development and can represent the challenges to be faced for a smooth conduction of a paediatric clinical trial. The need for trials and paediatric patient’s engagement to commensurate with the approved paediatric investigation plans is so high that it is crucial to correctly address key factors. Particular care should be taken to develop well-designed studies, with efficient management plans, experienced administrative and healthcare personnel, awareness of socio-cultural features of the geographic areas involved and good communication with patients and their families in order to ensure ‘trial preparedness’. A case study on a multinational paediatric clinical trial, presented within the recently ended research project ‘DEferiprone Evaluation in Paediatrics (DEEP)’, was reported to exemplify some of the challenges encountered by the authors and the actions taken to overcome them.

Background: We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512). This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated. Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model analysis were used to determine factors potentially influencing the timelines. The Cluster Analysis procedure was used to identify homogenous groups of cases. Result: The authorisation process was completed in 7.7 to 53.8 months in European countries and in 17.1 to 27.1 months in non-European countries. The main factors influencing these timelines were the requests for changes/clarifications in European countries and the different national legislations in non-European countries. Conclusion: This work confirms that the procedures and requirements for the clinical trial application of a paediatric trial are different. In the European Union, the timeframes for submission were generally harmonised but longer. In non-European countries, delays were caused by national dispositions but the entire authorisation process resulted faster with less requests from ECs/CAs. The upcoming application of Regulation (EU) 536/2014 is expected to harmonise practices in Europe and possibly outside. Networks on paediatric research acting at international level will be crucial in this effort.

PedCRIN is a Horizon 2020 project aimed to develop a paediatric component of ECRIN (European Clinical Research Infrastructure Network) including tools supporting the conduct of neonatal and paediatric trials.