Select Committee on European Union Thirty-Seventh Report


Letter from Rt Hon Jane Kennedy MP, Minister of State, Department of Health to the Chairman

  I am pleased to attach the Government response letter in respect of the House of Lords European Scrutiny Committee's report on the European Commission's proposals for a regulation on medicines for paediatric use.

25 March 2006

Government Response


  1.  The House of Lords European Union Committee (Sub-Committee G) published its report Paediatric Medicines: Proposed EU Regulation on 2 February 2006. This response sets out the Government's position on the recommendations contained in that report.

  2.  The report follows an Inquiry undertaken by the Committee to examine the European Commission's proposals for a Regulation on medicinal products for paediatric use (COM 2004 599 final).[19] The Commission's formal proposals were adopted on 29 September 2004. Negotiations on the proposals began in the Council in October 2004 and the Department of Health (DH)/Medicines and Healthcare products Regulatory Agency (MHRA) are leading in negotiations in Europe for the Government.


  3.  Increasing access to paediatric medicines which have been evaluated to the same standards of safety, quality and efficacy as those available to adults has been a concern in the UK for a number of years. In the UK, steps have been taken at a national level within the existing regulatory framework to produce, in the short to medium term, a measurable increase in appropriately labelled and formulated medicines for children, to increase information on paediatric use of medicines for prescribers, carers and patients and to facilitate the conduct of paediatric clinical trials. The Government considers, however, that a pan-European solution is required to address the current unacceptable situation and has been supportive of the Commission's initiative to develop a legislative proposal.

  4.  The Commission's proposed Regulation on medicines for paediatric use was developed in response to concerns expressed by all Member States, including the UK, which resulted in a Council Resolution of December 2000 which called on the Commission to develop proposals in the form of incentives and regulatory measures to ensure that all medicines are adapted to meet the specific needs of the paediatric population.

  5.  The proposals recognise the need for a regulatory approach which includes both incentives and requirements to ensure that new medicines for children and medicines already on the market meet the specific needs of the paediatric population while ensuring that children are not subjected to unnecessary clinical trials or delaying the authorisation of medicines for adults. The proposals aim to strike a balance between improving the availability of medicines licensed specifically for paediatric use and providing the stimulus for the pharmaceutical industry to undertake the necessary research. The Government's view is that the proposed Regulation will be key to addressing the current unacceptable situation whereby more than 50% of all medicines used to treat children in Europe have not been tested for specific use in children.

  6.  The proposed Regulation will be adopted though the co-decision procedure. Political agreement was reached on the draft Regulation at the Health Council in December 2005 under the UK Presidency. The next step is for the European Parliament to consider the proposal in its second reading. It is hoped that a common position will be achieved in the first half of 2006 and that the Regulation may be in place by around the end of 2006.

  7.  For ease of reference, we have numbered the Committee's recommendations to reflect the sequence in which they appeared in the Conclusions and Recommendations section of the Committee's report (pages 41- 43). Where different recommendations address overlapping issues we have provided a single overarching response.


1.  We conclude, in principle, from the evidence we have had that there is an overwhelming and urgent need to take effective action at European level to govern clinical trials in children and the authorisation of medicinal products for paediatric use with the minimum of delay.

  This Conclusion is consistent with the Government's view. Before a medicine is authorised for use in adults, the product must have undergone extensive testing including pre-clinical tests and clinical trials to ensure that it is safe, of high quality and effective. In contrast, most medicines used to treat children are not studied and licensed for use in children. This has been of concern to the Government for a number of years and we have encouraged the Commission to bring forward legislative proposals in this area.


2.  We conclude that the Clinical Trials Directive is an appropriate basis for this Regulation.

3.  We recommend that, in drawing up the guidelines underpinning the Clinical Trials Directive, the Government should ensure that particular attention is paid to the rights and capacity of children to give informed consent to trials. The guidelines must cover adequately and clearly the vulnerability of children, the possibility of conflict between the consent of parents and children involved in trials, the definition of informed consent and the distinction between consent and acquiescence in circumstances which are likely to arise during trials involving children, as well as the extent to which any trials concerned might benefit the child in question.

  The Clinical Trials Directive (2001/20/EC)[20] is not the basis for this Regulation. That Directive does, however, provide the legal text which sets out the requirements for conducting clinical trials and in the recitals to the proposed paediatrics Regulation there is a specific cross reference to the Clinical Trials Directive, making it clear that the controls and monitoring of studies in children conducted in the EU must comply with that Directive.

  The Government believes that the protection of those participating in clinical trials must be the over-riding priority and believes that the safeguards laid down in the Clinical Trials Directive, including the specific requirements for conducting clinical trials in children as well as the proposed measures contained in the Commission's proposals, provide a secure framework to ensure that the health, welfare and rights of children participating in clinical trials are protected. Obtaining informed consent from a person with parental responsibility or a legal representative is a pre-condition of a child's inclusion in a trial. However, it does not determine inclusion in a trial. That depends on a number of other factors including consideration of any views expressed by the child.

  The European Commission, in consultation with Member States, is preparing a guideline on the ethics of conducting clinical trials in children. It has asked the Ad Hoc Group on Clinical Trials, which has prepared guidance on the Clinical Trials Directive, to prepare a draft guideline for public consultation. The Government will make every effort to ensure that the guideline covers:

    —  rights and capacity of children to give informed consent,

    —  vulnerability of children;

    —  possibility of conflict between the consent of parents and children involved in trials;

    —  the difference between consent and acquiescence; and

    —  the extent to which the trial might benefit the child concerned.

  Officials from the MHRA will represent the Government's policy aims within the Ad Hoc Group. It is intended that the guideline will be in place when the proposed Regulation on medicines for paediatric use comes into force.

4.  We conclude that, in many other respects, the ethical validity and effectiveness of the Regulation will depend as critically on the guidelines to be developed as on the text of the Directive itself. While detailed discussion of such aspects is appropriate for legal, medical and pharmaceutical experts, who must be adequately consulted, we recommend that the underlying issues of public policy should be given wider attention and political oversight. We therefore welcome the Minister's agreement that the relevant officials should give us on-the-record briefing on the progress made in developing those guidelines at an appropriate time after the Directive has been agreed by the Council.

5.  We recommend that once the guidelines are drawn up the Government should ensure that they are fully understood by the medical and pharmaceutical professions and explained to the general public.

6.  We further recommend that the Government should ensure that the guidelines are kept fully up to date in line with changes in medical and scientific knowledge and practice.

  The guidelines underpinning the Regulation will be important in setting out how it will work in practice. The Government has given an undertaking to update the committee on developments at the appropriate time. We expect specific guidance to be developed in a number of areas including, for example, the rules of procedure for the proposed paediatric committee and guidance on the required format and content of an application for agreement of a paediatric investigation plan. The Commission will have responsibility under the comitology procedure for developing the guidelines in consultation with Member States. The Government will ensure that the guidelines are available to all stakeholders including healthcare professionals, patient organisations and the pharmaceutical industry. It is established practice for European guidelines resulting from pharmaceutical legislation to be updated regularly in the light of developments in medical and scientific knowledge and practice and the Government will ensure that they are.


7.  We recommend that the Clinical Trials Database should contain full details of all paediatric clinical trials, whether terminated prematurely or not. The database should be publicly available as a vital safeguard not only for those who might be involved in clinical trials but also for the medical profession and the paediatric population of Europe as a whole. This principle must be assured in the Regulation itself and in any guidelines developed from it.

  The Government agrees that the database established under the Clinical Trials Directive should contain full details of paediatric clinical trials conducted in the Community. In order to increase the availability of information on the use of medicines in children, and to avoid unnecessary duplication of studies in children, it is proposed that information concerning paediatric clinical trials entered into the database, as well as the details of the results of all paediatric clinical trials submitted to the competent authorities, should be accessible to the public. There may be some information that cannot be made public or cannot be made public immediately because of considerations relating to commercial confidentiality. The Commission will draw up guidance on which data would be entered on the database and which elements can be made accessible to the public.

8.  We recommend that the Government should give further and serious consideration to the proposal that products should be labelled in a way which indicates their suitability for use in children.

  The proposal regarding labelling has changed in the latest text of the Regulation. An abstract symbol, to be agreed by the Commission on a recommendation from the paediatric committee, will appear on the package label of all medicines authorised for paediatric use. Its meaning will be explained in the patient information leaflet. The symbol will not denote a particular age group. The Government will, through membership of the committee, have an input into the selection of a suitable symbol.

9.  It is abundantly clear from our evidence that children are not just young adults: their reaction to drugs varies considerably in relation to age and other factors and the newly-born are particularly vulnerable. We therefore recommend that any labelling scheme that is devised must take full account of this and make plain the risks of using products without consulting the relevant product information, especially for products which are available without prescription. Product information should also be summarised in clear, non-scientific language that leaves no doubt whatsoever about the risks of misuse and the need to follow carefully the dosage information.

  The Government supports the Commission's proposal for identifying products that have been studied in children. It is proposed that a symbol will be placed on the label of all medicines authorised for paediatric use whether they are supplied on prescription or not. The meaning of the symbol will be explained in the package leaflet. The Government does not believe that age specific symbols are required. The symbol will be selected by the paediatric committee within one year of the Regulation coming into force. The Government will, through membership of the committee have an input into the selection of a suitable symbol. The proposal also includes provisions to include more information on paediatric use in the product information, including advice on when and why not to use a product in a paediatric age group.

  Medicines labelling and patient information leaflets are already required to be set out in a manner which is accessible to the patient/carer so that the medicine can be used safely and effectively. In July 2005, the MHRA and the then Committee on Safety of Medicines (CSM) jointly published guidance for those involved in writing information for patients/carers on how best to meet their needs (Always Read the Leaflet—Getting the Best Information with Every Medicine). Included within this guidance is a particular section concerned with meeting the needs of specific patient groups including children and young people and how their communication needs can be met. The MHRA has recommended this guidance to the pharmaceutical industry and will monitor and update progress on this initiative, reporting to the Commission on Human Medicines in due course.


10.  We conclude that the European Medicines Agency (EMEA) is the appropriate body to oversee and co-ordinate the tasks envisaged by the proposed Directive. We welcome the Minister's assurances that the EMEA should be sufficiently resourced to carry out this task and that experience suggests it will work smoothly and effectively with the health services and agencies of Member States in doing so. But we recommend that these aspects should be kept under close review by the Government once the Directive enters into force.

11.  We conclude from the evidence we have been given that the overall composition of the paediatric committee is about right, we fear that any increase in the size of its permanent membership might run the risk of making it unwieldy.

12.  But, because the effective functioning of the Committee is crucial to the success of the Directive, we recommend that the Government should keep the composition of the Committee under review and ensure that it draws, where necessary, on relevant available ethical and practical expertise from Member States which may not be directly available through the Committee's own membership.

  The EMEA has a proven track record with 10 years experience of overseeing and co-ordinating European pharmaceutical legislation. The agency operates in close co-operation with the regulatory authorities in Member States and their networks of national experts. The members of the proposed paediatric committee may be supported by additional national experts, as necessary. As well as providing members for the proposed paediatric committee, the national regulatory authorities will be involved in, amongst other things, providing regulatory and scientific advice on paediatric drug development, assessing paediatric data, setting up clinical trials networks, and providing information on existing use of medicines in children. The Government agrees that all aspects of the Regulation, including the proposals in respect of the paediatric committee and the EMEA, should be kept under review. It is proposed that the operation of the Regulation will be reviewed within six years of entry into force.

  13.  We are unable to judge from the limited evidence and time available to us whether the proposal for funding research into paediatric use of off-patent medicines throughout the Community's research frame work programmes will be adequate. Nor are we able to assess the need for a separate Community-funded research programme on the lines of the Medicines Investigation for the Children of Europe (MICE) proposal. But we recommend that both aspects are adequately addressed, in consultation with interested parties, when the Commission review the working of the Regulation.

  The Government accepts this recommendation and believes that this will need to be considered when the Commission's review of the Regulation takes place. The Government believes there is a need for a study programme for research into paediatric use of off-patent medicines and at this stage takes the view that this can be achieved through the Community's research framework programme.


14.  We recognise that the package of incentives and rewards proposed in the Regulation are a political compromise, based on the acknowledged need to provide incentives and the apparent success of the US model. But we conclude that they are essentially a leap of faith: it is impossible to judge from the information we have been given whether these arrangements are likely to provide the necessary incentives to industry, whether they are likely to be equitable and proportionate, or whether they may give rise to excessive profits, penalise the health service of Member States or create unacceptable disadvantages for the manufacturers of generic products.

15.  We accept that a political compromise is necessary for the time being to launch the Regulation in the hope that it will bring the desired benefits for the children of Europe at a reasonable cost. But we recommend that the Government should continue to press the Commission to ensure that a full economic review of these proposals is made as soon as possible.

16.  If the Commission are unable to provide such a review within six years of implementation, as required by Article 49 of the Regulation, we recommend that they should be required to explain to the satisfaction of the Council why it would be premature too do so at that stage and to ensure that it is done as soon as possible after that.

17.  We also recommend that our successors should subject that review to very rigorous examination when it is submitted for Parliamentary scrutiny.

18.  In the meantime, we recommend that the Government should make every effort to improve on the adequacy of the estimates of costs and benefits produced in the regulatory impact assessment as soon as it is practicable to do so and to submit the results to Parliamentary scrutiny.

  The Government welcomes the support of the committee on its position for incentivising the pharmaceutical industry to carry out paediatric clinical trials. The Government believes that the incentive should be fair but not excessive, and supports the political position agreed at the Health Council in December for a six-month extension of the supplementary protection certificate.

  As demonstrated by the range in the estimated impact of the Regulation in the Rand Europe document and the Government's partial regulatory impact assessment it is not possible to accurately estimate the impact on the NHS at the present time. This information will not be available until medicines start to go through the process set out in the Regulation and come on to the market. This is why the Government argued and secured a review of the economic and health benefits of the Regulation to take place six years after it has come into force. However, if there is not sufficient data available at that time this review will be carried out within ten years of the Regulation coming into force. This position was agreed at the December Health Council, and the Government will continue to support this position.

  The Government supports the committee's recommendation to update the partial regulatory impact assessment. Once sufficient information is available to do this, the Government will submit it to the committee for scrutiny.


19.  In principle, we continue to believe that the Government should take a robust and consistent line in opposing proposals by the Commission which are, in the Government's view, brought forward for an inappropriate legal base. In this particular instance, in light of the overriding importance of the proposal and the need to make rapid progress in implementing it, we conclude that the Government is justified in agreeing to the present proposal with a Minute Statement recording its objection to the legal base.

  The Government welcomes the committee's endorsement of its position in relation to the legal base for this proposal and is grateful that the committee was able to grant scrutiny clearance before the Health Council on 9 December 2005. The committee will be aware that the Government's view was that Article 95 of the Treaty was not an appropriate legal basis for this Regulation and that Article 308 should have been used instead for the reasons invoked in case C-66/04 UK v EP and Council (the smoke flavourings case). Judgement in that case was given on 6 December 2005. The UK's arguments on the correct legal base for establishing a centralised procedure were rejected. Given what the Court said about the breadth of Article 95 and the measure of discretion conferred on the Community legislature as regards its use and the fact the proposed Regulation does not actually set up a new agency, but rather establishes a new committee within an existing agency, similar to the situation in the smoke flavourings case, the Government withdrew its objection to the legal base for the Regulation at the Health Council on 8-9 December 2005 and accordingly did not enter a minute statement. The Government will continue to take a robust line on legal base issues in the future.

Letter from the Chairman to Rt Hon Jane Kennedy MP

  Thank you for your letter dated 25 March enclosing the Government Response to the Report of the Committee's Inquiry into the above Proposal, which was received shortly before the House rose for the Easter Recess. The Response was considered by Sub-Committee G on 27 April.

  As you know, although the Report was only made for information, Baroness Thomas has put down a Question related to the Report which is expected to be debated in due course. We propose to publish the Government's Response in advance of that Debate.

  Before doing so, however, we wish to draw your attention to the enclosed submission of additional evidence from the Association of the British Pharmaceutical Industry (ABPI) which was only received on 18 April. A copy has already been sent to the responsible officials at the MHRA.

  As you will see, the ABPI are making representations about what they regard as the adverse effect of the two-year notice period required for applications for the six-month extension to the Supplementary Protection Certificate. They are asking for transitional arrangements that would modify the proposed Regulation. This follows informal representations made to the Committee by representatives of two pharmaceutical companies, AstraZeneca and Novartis, after the Report was published. But it was not raised in the evidence given to the Inquiry by the ABPI or any other witnesses.

  In the absence of any other evidence we are unable to take a view on what the ABPI have now said. But we believe that their submission is sufficiently important for it to be treated as supplementary evidence which should be made public and that the Government should be invited to submit views on it. We therefore propose to publish the ABPI submission together with the Government Response to the Inquiry before the Debate. It would therefore be most helpful if you could let us have the Government's response to the ABPI submission by Friday 19 May. That would enable us to publish both documents shortly afterwards in the hope that the Debate might be held sometime in June.

  I hope this is acceptable to you and look forward to your reply.

27 April 2006

19   Full title of the proposal is "Proposal for a Regulation of the European Parliament and of the Council on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/83/EC and Regulation (EC) No 726/2004. Back

20   Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Back

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