MHRA announces an exercise to update Summaries of Product Characteristics (SmPCs) to include paediatric information following completion of European work-sharing procedures

Inclusion of paediatric information in marketing authorisations following European work-sharing procedures

Background
The EU Paediatric Regulation (EC 1901/2006 as amended) now requires studies completed before the Regulation came into force (26 January 2007), but not already submitted, as well as studies completed in the paediatric population on an on-going basis to be sent to competent authorities (Articles 45 and 46). Assessment of these studies is being co-ordinated by the Co-ordination Group for Mutual Recognition and Decentralised Procedures, CMD(h) on a work-sharing basis and further information can be found on the CMD(h) pages of the Heads of Medicines Agencies website (external link).

Prior to the implementation of the Paediatric Regulation, there was a previous European work-sharing (EU WS) project on paediatric data, stimulated by the availability of data submitted to the Food and Drug Administration (FDA) (external link), which resulted in recommendations for updating SmPC and package leaflets with information on use of the product in children. Further details are provided on the paediatric data assessment pages of the CMD(h) website (external link). Outcomes of these procedures have been or are being published on the CMD(h) web-site together with a tabulated summary of the final recommendations for updating product information. The intention was that MAs for brand-leader products, and generic products as appropriate, would be updated by means of variations following the completion of the relevant work-sharing procedure.

The MHRA is aware that, for a variety of reasons, not all marketing authorisations (MAs) for the same drug substance have necessarily been updated with paediatric information following these earlier work-sharing procedures. We are therefore initiating a co-ordinated exercise with the aim of achieving consistent information for all affected products for the benefit of healthcare professionals and patients and their carers who can find variable information confusing. The exercise will take some months to complete for all the drug substances involved and further details will be published on the MHRA website as we progress.

We intend to adopt the same approach to updating national product information following the new EU work-sharing procedures which arise from Articles 45 and 46 of the Paediatric Regulation referred to above. The first of these procedures began in Autumn 2008.

Principles of the MHRA exercise
Marketing authorisation holders will be requested to submit the appropriate Type II variations by specified deadlines for their products which have a purely national licence or a licence which has been approved through a mutual recognition or decentralised procedure where the UK is RMS. One or two months' notice, depending on when the EU WS procedure closed, will be given. Companies will be strongly encouraged to submit the necessary variation to the reference MS where UK is a concerned MS for a particular product. Where an MA holder believes the authorisation should not include the recommended paediatric information and variations are thus not needed, a justification should be provided by the same deadline. If the recommendations following the CMD work-sharing scheme are followed, then the MHRA will undertake to process variations on an expedited 30 day timescale.

Variations to update products
Variation requests will be grouped by drug substance and requests sent out usually on a monthly basis with details of the expected deadlines for submission. Details of the drug substances and timelines for submission and approval will be published on the MHRA website as we proceed. To facilitate preparation of variation applications, we will, whenever possible, attach a template application form to our request. Applications should be limited to the changes arising from paediatric work-sharing procedure only.

Any wording recommended for the leaflet should be translated into appropriate language for UK leaflets and may reflect the company’s own in-house style. Submission of final leaflet or label/leaflet mock-ups is not a necessity at this stage but an undertaking must be given that the changes will be incorporated at the next reprint and within 3-6 months of approval (the usual expectation for variations). If not accompanying the requested variation, final mock-ups should be submitted either with another appropriate regulatory change or through a BROMI label and leaflet application. If the changes to the leaflet are sufficiently complex, additional user-testing should be considered. Any changes relating to paediatric information should also be incorporated into final leaflets for any pending applications which are approved subsequently.

The applications do not require supporting information or an expert overview except in cases where the exact wording proposed following EU WS assessment is not followed. Minor adjustments to accommodate existing SmPC/leaflet wording can be made but should be explained in the overview. Extensive amendments will result in a longer assessment process in line with standard Type II variation timescales and again, should be justified in an overview.

Submission process
For UK nationally approved products applications may be submitted directly by e-mail to specialpopulationsunit@mhra.gsi.gov.uk. If you would prefer to submit your application via the Sentinel portal please e-mail the Special Populations Group at specialpopulationsunit@mhra.gsi.gov.uk to inform us when you have submitted the application, including the portal submission reference number in the e-mail if possible. Applications submitted on CD should be marked for the attention of Sandra Ong, Room 10-113. It is not necessary for you to submit SmPC fragments as these will be updated on the Sentinel system by MHRA.

Applications where UK is CMS should be submitted to MHRA Information Processing Unit in the usual manner.

Fees
Please note that the usual fees will apply to these variations, but updates to all sections of the SmPC may be made in a single application and applications may be bulked in the usual way.

Further information
For further advice on this MHRA exercise please contact Dr Sarah Branch on 020 7084 2373 or Mrs Sandra Ong on 020 7084 3562 regarding submission of variations following EU Paediatric work-sharing procedures.

Requests issued

Drug substance	Date of request	Submission of variation deadline	Approval of variations deadline
Alendronate	7-14 November 2008	9 January 2009	6 February 2009
Gemcitabine	24-26 November 2008	23 January 2009	20 February 2009
Fluticasone (nasal spray formulations only)	15-17 December 2008	6 February 2009	6 March 2009
Carboplatin	16 March 2009	15 May 2009	12 June 2009
Budesonide (nebuliser suspension & inhalation powder only)	23 March 2009	22 May 2009	19 June 2009
Fosinopril	18 May 2009	10 July 2009	7 August 2009
Sumatriptan	21 May 2009	17 July 2009	14 August 2009
Fluvastatin	23 July 2009	18 September 2009	16 October 2009
Salmon calcitonin (Article 45)	6 August 2009	9 October 2009	6 November 2009
Ranitidine	10-11 August 2009	16 October 2009	13 November 2009
Isotretinoin	24 November 2009	22 January 2010	19 February 2010
Oxazepam	21 December 2009	22 January 2010	1 February 2010