Variations to implement changes to product information following European paediatric work-sharing procedures

Guidance updated

This guidance replaces earlier information on our website dated 18 November 2008 (MHRA exercise to update Summaries of Product Characteristics (SmPCs) following EU paediatric work-sharing procedures) and updated on 10 February 2010. Marketing authorisation (MA) holders need to update product information with the recommendations from the European paediatric work-sharing procedures. Since late 2008, data submitted under Article 45 or 46 of the ‘Paediatric Regulation’ (EC) No 1901/2006 (external link) as amended has been assessed according to these procedures.

On completion of the procedures, the final public paediatric assessment report is published on the Coordination Group for Mutual Recognition and Decentralised Procedures (CMDh) website (external link), together with the recommendations for updating the SmPCs and package leaflet, as appropriate.

In keeping with the EU Variation Regulation EU 1234/2008 these updates may be submitted as a Type IB C.I.3a variation, if the conditions are met. In a change to our previous guidance, we request that mock-ups of any amended patient information should be submitted with the variation application. We have also revised our guidance on grouping variations to include paediatric updates.

Classification of variations to update product information following paediatric work-sharing

According to the Commission’s classification guideline, variations to implement changes requested by competent authorities following the assessment of data submitted under Article 45/46 of the Paediatric Regulation may be submitted as a Type IB variation, provided there is no additional data submitted by the MA holder. If there are other changes which need to be supported by additional data, the variation will be classified as a Type II procedure.

The guideline also states that once new information becomes available which might require variation of the MA, it should be submitted immediately as a variation to the competent authorities, rather than awaiting assessment of those data against work-sharing or other procedures in the same category of follow-up variations.

MHRA procedure

Type IB variations
The MHRA accepts Type IB variations to update product information with the recommendations of paediatric Article 45 and 46 work-sharing procedures. The variations must be submitted in accordance with category C.I.3a of the European Commission guideline on classification - that is with no additional data for assessment.

Any changes in wording beyond those recommended by the paediatric work-sharing procedure, which require substantiation by new additional data, will be assessed as a Type II variation according to the appropriate timescale. All the changes to different sections of the SmPC as a result of paediatric work-sharing may be submitted in a single application, together with any consequential amendments to the package leaflet.

Supporting information
The applications do not require supporting information or an expert overview, except in cases where the exact wording proposed following EU work sharing 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 should be justified in an overview and supported by additional data if necessary.

MHRA requests
The MHRA will request variations from individual MA holders on publication of paediatric assessment reports on the CMDh website. However, our ability to meet the timescales recommended in the CMDh best practice guide will depend on the resources available and MA holders are encouraged to submit applications promptly without waiting for a letter of request. We will announce publication of assessment reports on our website.

Grouped variations
Following further experience with the new variations legislation, we have revised our advice on grouping paediatric work-sharing updates with other changes. Providing that the timelines are not compromised and no further assessment of data is required, paediatric work-sharing updates could be grouped with other change . Please note that, products in the same range containing the same active ingredient may be grouped together as a ‘bulk’ application.

Submission guidance for MA holders

• Submit all variation applications to the Information Processing Unit at the MHRA following the usual procedures and current guidance. Updated SmPC fragments should be included.
• Use the new variation applications form (external link), which is also available through the MHRA portal.
• Apply under category C.I.3 a) if wording in line with work-sharing recommendations and no new data submitted. If there is additional data, category C.I.3 b) (Type II) must be used.
• Ensure the scope of the variation (following EU paediatric Article 45/46 work-sharing procedure) is clearly stated on the application form so that the assessment can be allocated to the right team in the Agency.
• Attach the competent authority request to the cover letter of the application and relevant assessment report, if available. MHRA will accept variations without a specific request from a competent authority once a paediatric assessment report has been published on the CMDh website. A link to that report will suffice, instead of attaching the full document. Where the MA holder has submitted data which has been assessed during an Article 45 procedure, the end-of-procedure letter issued by the Rapporteur, including a request for submission of variations, may provide the necessary documentation.
• Attach updated SmPCs with exact wording recommended in final paediatric assessment report. Minor changes can be accommodated in a Type IB procedure but more extensive changes should be submitted as a Type II variation.
• Attach updated package leaflets where appropriate. Any wording recommended for the leaflet may be modified so that the language is suitable for UK leaflets and may reflect the company’s own in-house style. The final leaflet or label/leaflet mock-ups should be included in the submission, unless otherwise justified. If not accompanying the requested variation, final mock-ups should be submitted either with another appropriate regulatory change or through an Art 61(3) application. If the changes to the leaflet are sufficiently complex, additional user-testing should be considered. Changes relating to paediatric information should also be incorporated into final leaflets for any pending applications which are approved subsequently.
• Ensure appropriate fee is paid. The usual fees for Type IB and, where applicable, grouped variations and bulk applications will apply.

For further advice on implementing recommendations from European paediatric work-sharing procedures, please contact Dr Sarah Branch on 020 3080 6373 or send an email to specialpopulationsunit@mhra.gsi.gov.uk

Requests issued