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In order to improve the route to market for approved pediatric therapeutics, the current Pediatric Regulation in the EU and the Food and Drug Administration (FDA) Amendments Act (FDAAA) were both adopted in 2007..

IntroductionLimited information is available on the views of children taking medicines and participating in clinical trials. These views may contribute to a better understanding of what can be improved on in the development of medicines from their perspective.ObjectiveTo collect children’s views on taking medicines and participating in clinical trials.Materials and methodsA question-based survey was conducted among children living in European Union countries between January and August 2015.ResultsAlmost 900 children aged 10–17 years from Finland, Germany, Sweden, Spain and Hungary responded. Almost 40% had a chronic health condition. The most commonly used pharmaceutical forms were solid or liquid medicines for oral use and injectable medicines. Bad taste and pain during administration were reported as common problems. Of 785 respondents, 17% had been taking part in a clinical trial. Most respondents would potentially agree to take part in a clinical trial because the investigational medicine might improve their own health or that of other children. Concern that the investigational medicine might be harmful was the main reason to refuse participation, if asked to. Over half of the respondents were willing to learn more about clinical trials, preferably online.ConclusionsIt is necessary to involve children in the development of age-appropriate pharmaceutical forms and in the design of clinical trials. Children and their carers should be provided with age-appropriate medical information in the most suitable channels. We have identified some common problems that children experience when taking medicines, and we conclude that children are interested in learning more and giving their opinions on clinical trials.

Arzneimittel fur Kinder und Jugendliche werden in Deutschland und Europa erst seit rund einem Jahrzehnt systematisch so erforscht, wie dies bei Erwachsenen schon seit Jahrzehnten erfolgt. Auch heute werden noch viele Arzneimittel bei Kindern ohne systematische padiatrische Studien – zum Beispiel zur Dosierung oder zu Darreichungsformen – angewendet.

In Germany and throughout Europe, medicinal products for adults have been developed and evaluated systematically for decades. Medicinal products for children and adolescents, however, have only been researched for the past ten years. As a result, many medicinal products have been administered to children without systematic clinical trials, for example regarding dosage or pharmaceutical form.EU Regulation 1901/2006 aimes to close the gaps in the medical treatment of children and adolescents. In order to do so, the regulation provides for paediatric use marketing authorisations (PUMA) for previously authorised products no longer covered by intellectual property rights and also grants holders of such PUMA licenses further property rights. However, only two PUMA licenses have been applied for. Thus, the PUMA license instrument is hardly being used despite the fact that many medicinal products have a great potential for closing medical gaps for children and adolescents.In order to improve the situation regarding medicinal products for children and adolescents, this scientific symposium "More Medicines for Minors" intended to promote dialogue among the parties involved and to provide an opportunity to discuss reasons for the reluctance to apply for PUMA licenses. Speakers specialised in paediatric and adolescent medicine as well as those from licensing authorities, the Federal Joint Committee (Gemeinsamer Bundesausschuss, G‑BA), the pharmaceutical industry and the federal ministries presented problems and possible solutions from their point of view with the aim of making the PUMA license instrument more attractive.

Regulation (EC) No. 1901/2006 of the European Parliament and the Council dated 12 December 2008 on medicinal products for paediatric use is the result of a survey by the European Commission, concluding that children in the European Union are inadequately treated with medicinal products. The Regulation is addressed to the pharmaceutical industry with the intention to place medicinal products on the market and to the Member States to register all information on medicinal products for the treatment of children. The pharmaceutical industry will be obliged to conduct clinical trials in children for new medicinal products and medicinal products still under patent. This will be supported by incentives and rewards. As a consequence of the requirement to conduct clinical trials in children the framework and conditions have to be defined and ethical considerations have to be respected.

Die Harmonisierung des Arzneimittelrechts dauert auch nach einem uber 40-jahrigen Prozess weiterhin an. Der erste Schritt zur Harmonisierung der Anforderungen an die Zulassung und Uberwachung von Arzneimitteln erfolgte 1965 mit der ersten pharmazeutischen Richtlinie. Es wurden weitere europarechtliche Vorgaben in Form europaischer Richtlinien, die von den Mitgliedsstaaten in nationale Gesetze umgesetzt werden mussen, sowie Verordnungen, die unmittelbar in den Mitgliedsstaaten gelten und keiner nationalen Umsetzung bedurfen, verabschiedet. Ein vorerst letzter groser Schritt zur Harmonisierung des Arzneimittelmarktes erfolgte mit der Umsetzung der Anderungsrichtlinie 2004/27/EG im Rahmen des Pharma- Review 2002. So wurde zusatzlich zum bereits bestehenden zentralen Zulassungsverfahren und dem Verfahren der gegenseitigen Anerkennung das dezentrale Zulassungsverfahren eingefuhrt sowie die Erweiterung der Kompetenzen der Europaischen Arzneimittel-Agentur (EMEA) festgeschrieben. Die neuen Rechtsvorschriften zu Kinderarzneimitteln und neuartigen Therapien wurden uber eine Verordnung eingefuhrt.

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly. In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm

The harmonisation of the legislation for medicinal products is an on-going process even after 40 years of development. The first step for harmonising the requirements for the marketing authorisation and monitoring took place with the introduction of the first pharmaceutical directive in 1965. Further components of European legislation such as directives, which have to be transposed into national law by the Member States, and regulations, which take effect immediately, have been adopted since then. The latest fundamental progress made in the process of harmonising the European market for medicinal products was the adoption of Directive 2004/27/EG in the framework of the Pharma-Review 2002. In addition to the existing centralised procedure and mutual recognition procedure a decentralised procedure and the enlargement of the area of authority of the European Medicines Agency were introduced. Lately new laws for medicinal products for children and advanced therapies were introduced through a regulation.