Explanatory Memorandum to COM(2004)599 - Medicinal products for paediatric use - Main contents
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This page contains a limited version of this dossier in the EU Monitor.
| dossier | COM(2004)599 - Medicinal products for paediatric use. |
|---|---|
| source | COM(2004)599  |
| date | 29-09-2004 |
1. Introduction and background
The public health concern and its causes
The paediatric population is a vulnerable group with developmental, physiological and psychological differences from adults, which makes age and development related research of medicines particularly important. In contrast to the situation in adults, more than 50% of the medicines used to treat the children of Europe have not been tested and are not authorised for use in children: the health and therefore quality of life of the children of Europe may suffer from a lack of testing and authorisation of medicines for their use.
Although there may be concerns voiced about conducting trials in the paediatric population, this has to be balanced by the ethical issues related to giving medicines to a population in which they have not been tested and therefore their effects, positive or negative, are unknown. In order to address the concerns about trials in children, the EU Directive on clinical trials1 lays down specific requirements to protect children who take part in clinical trials in the EU.
Related initiatives: EU Orphan Regulation and US legislation on medicines for children
The absence of research into treatments for rare diseases led the Commission to propose the Regulation on orphan medicinal products, subsequently adopted in December 1999. This Regulation has proved successful in stimulating research leading to the authorisation of medicines to treat rare diseases.
In the US, specific legislation to encourage the performance of clinical trials in children has been introduced, containing combined measures of incentives and obligations which have proven successful in stimulating the development of medicinal products for paediatric use.
Council Resolution
The Council Resolution of 14 December 2000 called on the Commission to make proposals in the form of incentives, regulatory measures or other supporting measures in respect of clinical research and development to ensure that new medicinal products for children and medicinal products already on the market are fully adapted to the specific needs of children.
2. Justification
Objective
The overall policy objective is to improve the health of the children of Europe by increasing the research, development and authorisation of medicines for use in children.
General objectives are: to increase the development of medicines for use in children; to ensure that medicines used to treat children are subject to high quality research; to ensure that medicines used to treat children are appropriately authorised for use in children; to improve the information available on the use of medicines in children, and; to achieve these objectives without subjecting children to unnecessary clinical trials and in full compliance with the EU Clinical Trials Directive.
Scope, legal basis and procedure
The proposed system covers medicinal products for human use within the meaning of Directive 2001/83/EC.
The proposal is based on Article 95 of the EC Treaty. Article 95, which prescribes the codecision procedure described in Article 251, is the legal basis for achieving the aims set out in Article 14 of the Treaty, which includes the free movement of goods (Article 14(2)), in this case human medicinal products. While taking account of the fact that any regulations on the manufacture and distribution of medicinal products must be fundamentally aimed at safeguarding public health, this aim must be achieved by means that do not impede the free movement of medicinal products within the Community. Since the Amsterdam Treaty came into force, all legislative provisions adopted by the European Parliament and the Council in this field have been adopted on the basis of that Article, since the differences between the national legislative, regulatory and administrative provisions on medicinal products tend to hinder intra-Community trade and therefore directly affect the operation of the internal market. Any action to promote the development and authorisation of medicinal products for paediatric use is justified at a European level with a view to preventing or eliminating these obstacles.
Subsidiarity and proportionality
The proposal builds on the experience gained with the existing regulatory framework for medicines in Europe and learns from the requirements and incentives for paediatric medicines in the US and the EU orphan regulation. On the basis of the available evidence it is concluded that it is unlikely that the current public health issue regarding medicines for children will be resolved in the EU until a specific legislative system is put in place.
Community action allows the best possible use of the instruments set up in the pharmaceutical sector to complete the internal market. In addition, authorisation of medicines for children is a Europe-wide issue. However, Member States will have an important role in the fulfilment of the objectives of the proposal.
Legislative and administrative simplification
All the key measures in the proposal build on or strengthen the existing framework for the regulation of medicinal products. This proposal directly interfaces with five existing Community legislative texts: Directive 2001/83/EC of the European Parliament and of the Council of 6 November 20012 which sets the framework for the regulation of medicinal products; Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 20043 which establishes the European Medicines Agency (EMEA) and created the centralised authorisation procedure for medicinal products; Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 which provides a framework for the regulation and conduct of clinical trials in the Community; Regulation (EC) No 141/2000 of the European Parliament and of the Council which establishes a Community system for the designation of medicinal products as orphan medicinal products and incentives to stimulate their development and authorisation4 and; Council Regulation (EEC) No 1768/92 of 18 June 19925 which created the Supplementary Protection Certificate.
This proposal for a regulation establishes a precise legal framework, however, where more detailed implementing provisions are required, a Commission regulation is foreseen and it is proposed that further provisions be adopted by the Commission as guidelines, in consultation with the Member States, the EMEA and the parties concerned.
Consistency with other Community policies
Consistency will be sought with activities in the areas of research and development and health and consumer protection.
Outside consultation
Interested parties have been widely consulted on this proposal. Detail on the consultation conducted by the Commission is included in the Extended Impact Assessment that accompanies this proposal.
Evaluation of the proposal: Extended impact assessment
This proposal has been the subject of a Commission extended impact assessment, attached to this proposal, which is based on data collected by an independent contracted study.
3. Presentation
A brief description of the main elements of the proposal is hereby provided. For a more detailed description, we refer to the Commission’s explanatory document attached to this proposal.
Key measures included in the proposal
The Paediatric Committee
A committee with expertise in all aspects related to medicines for children is central to the proposal and its operation. The Paediatric Committee will be responsible primarily for the assessment and agreement of paediatric investigation plans and requests for waivers and deferrals described below. In addition it may assess compliance with paediatric investigation plans and be asked to assess the results of studies. In all its work it will consider the potential significant therapeutic benefits of studies in children including the need to avoid unnecessary studies, it will follow existing Community requirements and will avoid any delay in the authorisation of medicines for other populations as a result of the requirements for studies in children.
Marketing authorisation requirements
The paediatric investigation plan will be the document upon which the studies in children are based and will have to be agreed by the Paediatric Committee. When assessing such plans the Paediatric Committee will have to take into consideration two overarching principles: that studies should only be performed if there is a potential therapeutic benefit to children (and avoiding duplication of studies) and that the requirements for studies in children should not delay the authorisation of medicines for other populations.
A core measure is a new requirement for the results of all studies performed in accordance with a completed, agreed paediatric investigation plan to be presented at the time of applications, unless a waiver or a deferral has been granted. This core requirement has been included to ensure that medicines are developed for children based on their therapeutic needs. The paediatric investigation plan will be the basis upon which compliance with this requirement is judged.
Waivers from the requirements
Not all medicines being developed for adults will be suitable for children or will be needed to treat children and unnecessary studies in children should be avoided. To deal with such situations a system of waivers from the requirements described above is proposed. The Paediatric Committee will start work as soon as it is set up, on lists of waivers of specific medicinal products and classes of medicinal product. For products not included in the published lists, a simple procedure is proposed for companies to request waivers.
Deferrals from the timing of initiation or completion of studies in children
Sometimes studies in children will be more appropriate when there exists some initial experience on use of a product in adults or studies in children might take longer than studies in adults. This might apply to the entire paediatric population or just a subset. Therefore, to deal with this situation, a system of deferrals is proposed together with a procedure for agreeing them with the Paediatric Committee.
Marketing authorisation procedures
The procedures set out in existing pharmaceutical legislation are not altered by the proposals. The requirements above will require the Competent Authorities to check compliance with the agreed paediatric investigation plan at the existing validation step for marketing authorisation applications. The assessment of safety, quality and efficacy of medicines for children and the granting of marketing authorisations remain the remit of the Competent Authorities. To increase the availability of medicines for children across the Community, because the requirements in the proposals are linked to Community-wide rewards and to prevent the distortion of free trade within the Community, it is proposed that an application for a marketing authorisation including at least one paediatric indication based on the results of an agreed paediatric investigation plan will have access to the centralised Community procedure.
The Paediatric Use Marketing Authorisation (PUMA)
In order to establish a vehicle for providing incentives for off-patent medicines, a new type of marketing authorisation, the Paediatric Use Marketing Authorisation (PUMA) is proposed. A PUMA will utilise existing marketing authorisation procedures but is specifically for medicinal products developed exclusively for use in children.
The name of the medicinal product granted a PUMA can utilise the existing brand name of the corresponding product authorised for adults but the product names of all medicines granted a PUMA will include a superscript of the letter “P” to aid recognition and prescribing. Thus, pharmaceutical companies will be able to capitalise on existing brand recognition while benefiting from the data protection associated with a new marketing authorisation. The data protection period associated with the PUMA may prove more valuable in light of the recent case law of the European Court of Justice concerning the interpretation of data protection rules6.
An application for a PUMA will require the submission of data necessary to establish safety, quality and efficacy specifically in children, collected in accordance with an agreed paediatric investigation plan. However, an application for a PUMA may refer to data contained in the dossier of a medicinal product which is or has been authorised in the Community.
Extension of the duration of the supplementary protection certificate
For new medicines and for products covered by a patent or a Supplementary Protection Certificate (SPC), if all the measures included in the agreed paediatric investigation plan are complied with, if the product is authorised in all Member States and if relevant information on the results of studies is included in product information, the six-month SPC extension will be granted. The mechanism for this will be the inclusion of a statement in the marketing authorisation that these measures have been met. Companies will then be able to present the marketing authorisation to patent offices that will then award the SPC extension. The need to have a marketing authorisation in all Member States is to prevent a Community-wide reward without Community-wide benefits to child-health. Because the reward is for conducting studies in children and not for demonstrating that a product is safe and effective in children, the reward will be granted even when a paediatric indication is not granted. However, relevant information on use in paediatric populations will have to be included in authorised product information.
Extended market exclusivity for orphan medicinal products
Under the EU orphan regulation, medicinal products designated as orphan medicinal products gain ten-years of market exclusivity on the granting of a marketing authorisation in the orphan indication. As such products are frequently not patent protected the reward of SPC extension can not be applied and when they are patent-protected, SPC extension would provide a double incentive. Therefore it is proposed to extend the ten-year period of orphan market exclusivity to twelve-years if the requirements for data on use in children are fully met.
Paediatric study programme: Medicines Investigation for the Children of Europe (MICE)
An additional tool for promoting high quality, ethical research that may lead to the development and authorisation of medicines for children should be the provision of funding for studies into the paediatric use of medicines not covered by a patent or a supplementary protection certificate. The Commission intends to examine the possibility of setting up a paediatric study programme: Medicines Investigation for the Children of Europe, taking into consideration existing Community Programmes.
Information on the use of medicines for children
One of the objectives of this proposal is to increase the information available on the use of medicines for children. Through increased availability of information, the safe and effective use of medicines for children can be increased so promoting public health. In addition, availability of this information with help prevent the duplication of studies in children and the conduct of unnecessary studies in children.
The Clinical Trials Directive establishes a Community database of clinical trials (EudraCT). It is proposed to build onto this database an information resource of all ongoing and terminated paediatric studies conducted both in the Community and in third countries.
In addition, based on a survey of existing use of medicines in Europe, an inventory of therapeutic needs of children will be established by the Paediatric Committee.
It is also proposed to create a Community network to link together national networks and clinical trial centres in order to build up the necessary competences at a European level and to facilitate the conduct of studies, to increase co-operation and avoid duplication of studies.
Pharmaceutical companies have, in some cases, already conducted clinical trials in children. However, frequently, the results of these studies have not been submitted to Competent Authorities and have not resulted in updates to product information. To deal with this issue, it is proposed that any studies completed before this proposed legislation is adopted will not be eligible for the rewards and incentives proposed for the EU. They will, however, be taken into account for the requirements contained in the proposals and it will be mandatory for companies to submit the studies to the competent authorities once this proposed legislation is adopted.
Other measures
The interface between the Committee for Medicinal Products for Human Use, its Scientific Advice Working Group and other Community committees and working groups on medicines and the Paediatric Committee will be managed by the EMEA. In addition, free scientific advice from the EMEA to sponsors developing medicines for children is proposed.
The proposals presented will place demands on competent authorities and particularly on the EMEA. It is proposed to increase the Community subsidy, to be allocated to the EMEA to take account of the new tasks. A financial statement accompanies this proposal.