In this section...
- Latest news
- Paediatric assessment work in the MHRA
- Commission on Human Medicines Expert Advisory Group on Paediatric Medicines
- EU Regulation on paediatric medicines
- UK strategy document on medicines for children
- Requests for data
- Assessment reports of paediatric data by MHRA
- Assessment reports of paediatric data - EU worksharing exercise
- Assessment reports of paediatric data
- Useful references: paediatric guidelines and other publications
- Links to further information
- Contact for further information
Welcome to our section on medicines for children. We will be adding further material to this section as work progresses and we welcome suggestions for improvements or additions.
Latest news7 May 2013: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
26 November 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
14 September 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
16 July 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
3 May 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
15 March 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
24 February 2012: Latest Press Release from PDCO which includes statistics on PIP submissions and opinions
30 January 2012: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
25 November 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
30 September 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
August 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
8 July 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
9 June 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
6 June 2011: Press release - More exact paracetamol dosing for children to be introduced
26 May 2011: Publication of assessment reports for European Article 45 paediatric work-sharing procedures
3 May 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
17 March 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
7 February 2011: Publication of assessment reports for European Article 45 paediatric work-sharing procedures
4 February 2011: Updated guidance: Variations to implement changes to product information following European paediatric work-sharing procedures
12 January 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
5 January 2011: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
5 November 2010: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
3 November 2010: Updated assessment reports for European Article 45 paediatric work-sharing procedures
19 October 2010: Publication of assessment reports for European Article 45 paediatric work-sharing procedures
8 September 2010: Publication of assessment reports for European Article 45 paediatric work-sharing procedures
11 August 2010: Publication of assessment reports for European Article 45 and 46 paediatric work-sharing procedures
Before any 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. The same may not be true for medicines used to treat children. Over 50% of the medicines used in children may not have been studied in this age group. In the European Union, the paediatric population (0-18 years) represents about 75 million people, that is 20% of the total population. This is a vulnerable group with developmental, physiological and psychological differences from adults, which makes age and development related research particularly important.
The absence of suitable authorised medicinal products to treat conditions in children is an issue that has been of concern for some time. Pharmaceutical companies have been reluctant to invest in developing specific treatments or adapting existing medicines to meet the needs of the paediatric population, mainly because the market is small and therefore of lower commercial interest and the studies can be difficult, long and expensive. In addition, developing a suitable formulation which can provide an exact dose, for example a syrup, may be technically difficult and expensive on an industrial scale. This often leaves no alternative to the prescriber than to use 'off-label' and unauthorised products, without evidence-based information to guide prescribing and give information about the risk-benefit assessment.
Why do we need to conduct trials in children?
Although there may be ethical concerns about conducting trials in the paediatric population, this has to be balanced by the ethical concerns about giving medicines to a population in which they have not been tested. The new European Union (EU) Directive on clinical trials lays down specific requirements to protect children who take part in clinical trials in the EU.
The paediatric population is not a homogeneous group; it ranges from pre-term newborns, through toddlers and children to adolescents. They are not miniature versions of adults. Specific clinical trials in paediatric populations are normally required due to age-related differences in the drug handling or drug effects which may lead to different dose requirements to achieve efficacy or to avoid adverse effects. Recently, paediatric studies conducted in response to US legislation led to 34 labels containing new paediatric information for established medicines between July 1998 and April 2002. In 12 cases (or just over one third) the new labels included important new dosing/pharmacokinetic or safety information which had an impact on the safe and effective use of the medicine in the paediatric population. Further information on this study is available on the US Food and Drug Administration (FDA) website (external link). Without such specific studies in the paediatric population this important information would not be available. In addition, there may be practical problems of administration, for example, difficulties swallowing tablets if a syrup is not available or, more significantly, serious calculation errors when using adult formulations to obtain paediatric dosages.
Paediatric assessment work in the MHRA
Development of medicines for children should in principle be part of the normal lifecycle evolution of a drug and thus paediatric assessment work in the MHRA is distributed to our licensing or vigilance assessment teams in accordance with our usual practices. However, the Paediatric Regulation (Regulation EC No.1901/2006 as amended) has introduced some regulatory procedures which are unique to the use of medicines in children, and such assessment work is conducted by the Special Populations Group in the VRMM Division.
Paediatric Investigation Plans (PIP)
Applications for agreement of PIPs must be submitted to the European Medicines Agency according to the procedures outlined on its website (external link). The Special Populations Group assesses PIPs where the UK has been appointed as Rapporteur or Co-Rapporteur by the Paediatric Committee. Comments on other PIPs may also be provided by Paediatric Committee members as part of the procedure.
Paediatric studies completed before or after entry onto force
The Special Populations Group is responsible for the assessment of data submitted under Article 45 or 46 which is the subject of a European paediatric work-sharing procedure where the UK has been appointed Rapporteur by CMD(h).
The Special Populations Group will also assess any variations to update marketing authorisations with information relating to paediatric use as a result of recommendations made following European work-sharing procedures. Information on submission of such variations is available:
New medicinal products and variations supported by paediatric information
Where paediatric data has been submitted to the MHRA in support of applications for new medicinal products (containing either new or existing active substances) or variations to add new paediatric indications or posology, then this data will generally be assessed by the appropriate chemical or biological Product Lifecycle Assessment Team in Licensing Division according to therapeutic area in the usual manner. Likewise, black-triangle or non-black triangle safety variations involving paediatric data will be assessed by the relevant team in the Risk Management or Therapeutic Review Groups of VRMM Division respectively.
Please note that where demonstration of compliance with a PIP is required for a particular application, the compliance check will be the joint responsibility of the Information Processing Unit and the relevant assessment team. The MHRA is currently requesting a compliance opinion from the Paediatric Committee, if necessary, before completing validation if one has not already been sought and supplied by the company. Further information is available:
It would be helpful if marketing authorisation holders could bear this information in mind when compiling documentation for submission to the MHRA. The flow of paediatric submissions between applicants, MHRA assessment teams and European scientific committees is presented in the diagram below.
For further enquiries on paediatric submissions, please send an email to email@example.com.
Commission on Human Medicines Expert Advisory Group on Paediatric Medicines
The Commission on Human Medicines (CHM) Expert Advisory Group on Paediatric Medicines (PMEAG) was established in 2006. It replaces the Committee on Safety of Medicines (CSM) Paediatric Medicines Working Group (PMWG) which was established in July 2000. Its remit is to advise the CHM on the safety, quality and efficacy of medicines for paediatric use, and on the implementation of the Department of Health/MHRA paediatric strategy, the EU paediatric worksharing project, and the European regulation on medicines for paediatric use (Regulation (EC) No 1901/2006).
EU Regulation on paediatric medicines
The EU Regulation on Paediatric Medicines1 was adopted on 12 December 2006 and came into force on 26 January 2007.
Content of final Regulation
The Regulation aims to establish a legislative framework that will fulfil the following main objectives:
- increased availability of medicines specifically adapted and licensed for use in the paediatric population
- increased information available to the patient/carer and prescriber about the use of medicines in children, including clinical trial data
- increase in high quality research into medicines for children.
These will be achieved through a system of requirements and incentives.
Work began on the draft texts in the Council Working Group in late October 2004. Achieving progress on the Regulation was a priority of the UK Presidency of the EU and political agreement on a text was reached in December 2005. A second reading agreement between the Council the European Parliament, and the European Commission was achieved in June 2006.
The main elements of the finalised Regulation include:
- the establishment of a new body, the Paediatric Committee, sited at the European Medicines Agency (EMEA)
- for new products and certain changes to the marketing authorisation for products still covered by patent protection
- a requirement for paediatric data based on a paediatric investigation plan (PIP)*
- a six-month extension of the supplementary protection certificate (SPC) if information arising from a completed PIP is incorporated into the Summary of Product Characteristics (SmPC)
- for orphan medicinal products
- a two-year extension of market exclusivity if information arising from a completed PIP is incorporated into the Summary of Product Characteristics (SmPC)
- for off-patent products
- a new category of marketing authorisation called the paediatric use marketing authorisation which will be associated with a ten-year period of data and market protection
- a European database of paediatric clinical trials, part of which will be publicly accessible
- a requirement to submit data from paediatric clinical trials to the regulatory authorities
- coordination of a European Paediatric Clinical Trials Network.
- funding for the study of off-patent medicines provided through the Community framework programmes
- an identifying symbol on the package of all products authorised for use in children.
* This does not become law until 18 months after entry into force of the Regulation
The European Commission’s original proposal for a Regulation on medicines for paediatric use as well as supportive explanatory documents are available on the European Commission website:
European Commission website: Medicines for Children (external link)
The final Regulations and a summary of the Regulations are available below:
Regulation (EC) No 1901/2006 (207Kb)
Regulation (EC) No 1902/2006 (55Kb)
Frequently asked questions
The following document has been issued by the EMEA and addresses some questions relating to the Paediatric Regulation that are frequently asked by companies submitting applications to the EMEA.
1 Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004 (Official Journal L378,27/12/2006 p1-19)
UK strategy document on medicines for children
The MHRA and Department of Health have produced a strategy document on medicines for children along with accompanying questions and answers:
Requests for data
While awaiting finalisation of the legislation, we have identified a number of national initiatives to make progress in this area through the current regulatory framework. One of these initiatives is to formally request completed paediatric study data from companies, where this is known to exist. The MHRA policy on requesting paediatric data from companies and the list of companies contacted is available below:
Assessment reports of paediatric data by MHRA
In line with the aim to make information on the paediatric use of medicines available to health professionals and carers/patients, this section contains the assessment reports of the paediatric data submitted following a direct request from the MHRA.>
Assessment reports of paediatric data - EU worksharing exercise
The EU worksharing exercise is a collaborative process whereby the Member States are sharing the work of assessing paediatric data previously submitted to the FDA (Food and Drug Administration).
By licensed name
By active constituent
|Cosopt (dorzolamide/timolol) eye drops solution (234Kb)||Budesonide (Pulmicort Nebuliser Suspension 0.125/ 0.25/ 0.5 mg/ml) (346Kb)|
|Detrusitol/Detrusitol SR/Detsel/Protol SR (tolterodine tartrate) (457Kb)||Budesonide (Pulmicort Turbuhaler Powder for Inhalation 100 µg, 200 µg, 400 µg) (454Kb)|
|Durogesic Fentanyl Transdermal Patch (452Kb)||Carboplatin (Paraplatin) (241Kb)|
Paraplatin (carboplatin) (241Kb)
Fluticasone Propionate (119Kb)
Assessment reports of paediatric data
The following assessment reports relate to paediatric data submitted by a marketing authorisation holder outside the MHRA national initiative on paediatric data and the European worksharing exercise.
By licensed name
By active constituent
Useful references: paediatric guidelines and other publications
Medicines for Children. 2nd ed. RCPCH, NPPG; 2003. ISBN 190095468 0.
'Medicines for Children' is a UK paediatric formulary produced jointly by the Royal College of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists Group.
Links to further information
Links to current MHRA drug-specific safety issues
The majority of SSRIs - the most commonly prescribed type of antidepressants - are not suitable to be used by under 18s.
The Committee on Safety of Medicines (CSM) keeps the safety of the MMR vaccine under continual review.
Aspirin and Reye's syndrome (80Kb)
From 1 October 2003 all products containing aspirin were required to include a statutory label warning - "Do not give to children under 16 years, unless on the advice of a doctor".
The Medicines (Child Safety) Regulations (SI 2003/2317) came into force on 1 October 2003. Medicines containing aspirin, paracetamol and more than 24 mg of elemental iron must be placed on the market in packaging which has been shown to be child resistant.
Current Problems in Pharmacovigilance' articles
Inhaled corticosteroids and adrenal suppression in children (October 2002;26:7)
Adrenal suppression may be under-recognised.
Prescribing advice updated to minimise the risk of systemic adverse effects.
Oral iron supplements: accidental overdose may be fatal in children (August 2001;27:14)
Iron, in overdose, is highly toxic and safe storage of iron preparations is essential.
Alfacalcidol (One-Alpha drops): accidental overdose (February 2001;27:3)
Alfacalcidol drops should be prescribed in nanograms or micrograms, not millilitres.
Cisapride (Prepulsid) withdrawn (September 2000;27:9-10))
Suspension of product licences due to serious ventricular arrhythmias and an unfavourable risk:benefit balance. On 10 March 2004, the Committee on Safety of Medicines discussed the unlicensed supply of cisapride in the UK.
No evidence of serious systemic adverse reactions.
Dosage regimen revised, reflecting new pharmacokinetic data. Prescribers should be alert for warning symptoms and signs suggestive of bone-marrow failure.
Antiretroviral drugs in pregnancy and mitochondrial cytopathy in infants (November 1999;25:15)
The benefits of zidovudine in preventing vertical HIV transmission far exceed the risk of mitochondrial cytopathy.
Inhaled and nasal corticosteroids: safety (May 1998;24:8)
Systemic adverse effects may occur, particularly with prolonged, high dose therapy
Excess dosing and concomitant valproate are probable risk factors.
Links to further information on other websites* (all external links)
We have included links to other websites which include useful information about the use of medicines in children.
The Children's National Service Framework website - medicines management and prescribing for children has been recognised as a high priority for the Children's National Service Framework. The Medicines Group was established on the 20 June 2002 with the aim of making sure that children’s medicines are not only clinically effective but are also delivered in ways that meet their needs and respects their wishes. Information on the Medicines Group is available on the Children's NSF site.
* Please note that the Medicines and Healthcare products Regulatory Agency (MHRA) does not accept responsibility for the content of other sites. This list exists only for the interest and convenience of those who use this section of the MHRA site. We do not necessarily recommend or condone the included site. We cannot guarantee that these links will work all of the time and we have no control over availability of the linked pages.
Contact for further information
For further information on this part of our site, please contact the Central Enquiry Point, 4.T, 151 Buckingham Palace Road, Victoria, London, SW1W 9SZ, telephone 020 3080 6000 or email firstname.lastname@example.org.