In this section...
A new European variations regulation came into force on 1 January 2010 and replaces Regulations 1084/2003/EC and 1085/2003/EC. Commission Regulation 1234/2008 concerns variations handled in Mutual Recognition or Centralised Procedures.
However, following a consultation earlier this year UK health ministers have agreed that the UK will adopt these new rules for all variations to marketing authorisations, including those held only in the UK. Therefore from 1 January 2010, the new classification systems and procedural rules will apply in full. In parallel, an amending UK fees regulation is to be implemented in order to establish fees for the new types of work specified in the Commission regulation.
New UK guidance has been produced and is published below under 'What's new'. Further guidance will be added to this site over the next month in preparation for the implementation, including details of the revised application form (including the MHRA portal form) and associated user guides.
What's new
19 Aug 2010: Variations legislation 2010 - details of our experience to date, submissions audit and update to FAQs
The new Variations Regulation (EC/1234/2008) (external link) took effect on 1 January 2010. This immediately applied to variations to marketing authorisations covered by European procedures. However, the MHRA has also applied it to purely national variation applications since then.
The system has now been in operation for six months (as at August 2010) and is still relatively new for some companies. Depending upon how many Type IA variations a company may have had to manage during this period, experience is still being gained.
To help ensure that companies are submitting the new Type IA notifications correctly we have published details of our experience to date and an audit of submissions made in June 2010. We have also updated the FAQs.
Variations to licences: Experience to date
Variations to licences: Audit of new Type IA variations
FAQs for variations submitted after 1 January 2010
23 December 2009: Latest guidelines and variation application form published
The European Commission have now published on their website the final versions of new guidelines for 'operation of the procedures' and 'details of the various categories' (classification) for variations under the new Regulation coming into force on 1 January 2010. As previously announced, the UK is adopting the relevant procedural changes and the new classification system also for non-MR variations to purely National marketing authorisations from the same date.
A new variation application form (VAF) is published and must also be used from 1 January 2010 for all marketing authorisation (MA) variations submissions. The published VAF is considered to be a 'stable document' despite at present being labelled as 'Draft'. From 1 January 2010, the MHRA will also launch a new Portal version of the VAF.
The guidelines and the new VAF can be found on the European Commission’s (EC) website.
Some explanatory notes (user guidance) on how to use the new VAF has also been developed by the European Medicines Agency and CMDh and will be published on the EC and the CMDh websites. Meanwhile a copy is provided here.
EMA/CMD(h) explanatory notes on variation application form
(97Kb)
In January, the MHRA will also be updating its own guidance documents and will publish Q&As derived from conferences and enquiries. If you need advice on submitting a variation application under the new rules, contact our Variations Queries helpdesk by email: variationqueries@mhra.gsi.gov.uk
30 November 2009: UK national MA variations guidance published
This new guidance is provided to assist those making variation applications to the MHRA as from 1 January 2010, following the implementation of a new Commission regulation and its adoption for UK national variations.
UK national MA variations guidance (72Kb)
14 July 2009: Streamlining the apporval process of safety variation applications
The Therapeutic Review Group of the Vigilance and Risk Management of Medicines (VRMM) Division is to pilot a new process designed to streamline and speed up the approval process of safety variation applications. The process will apply only to national applications where the safety issue is agreed but there is a need to finalise the wording of the Summary of Product Characteristics (SPC) or patient information leaflet (PIL). This procedure has been developed in consultation with industry and the initial pilot will run until the end of August 2009.
Please send any enquiries or comments to the Pharmacovigilance Service mailbox: pharmacovigilanceservice@mhra.gsi.gov.uk
National Type II safety variations 'Request for Further Information' (RFI): Pilot project plan (159Kb)
26 March 2009: Review of the EU variations regulation: European Commission consultation on draft guidelines
The European Commission has published a public consultation on draft guidelines on the operation of the procedures laid down in Chapters II, III and IV of the new Variations Regulation (EC) no 1234/2008. The new Variations Regulation will apply from 1 January 2010 to variations to marketing authorisations granted via the Mutual Recognition, Decentralised and Centralised Procedures. The Commission's consultation can be found via the link below:
Public Consultation Paper for the preparation of guidelines on the operation of the variation procedures (external link)
Public Consultation Paper for the preparation of guidelines on the details of the various categories of variations (external link)
The Commission has asked for comments on the draft guidelines by 18 May 2009.
23 January 2009: Acetonitrile shortage
There is currently a global shortage of acetonitrile, a solvent which is widely used in the pharmaceutical industry for the analysis of drug substances and drug products and for manufacturing drug substances. This shortage may persist throughout 2009 and many solvent suppliers have recently announced restrictions on supplies of acetonitrile. As a consequence, companies are seeking to use alternative solvents or analytical methods to minimise the impact of this shortage. Advice on changes requiring variation submissions to update Marketing Authorisations can be found using the following link.
Global shortage of acetonitrile: Advice to the pharmaceutical industry on changes requiring variation submissions to update Marketing Authorisations
MHRA procedures
The MHRA has revised its procedures for processing applications to vary marketing authorisations in line with the new European legislation. We will follow the principles of the Mutual Recognition Facilitation Group best practice guide (MRFG BPG) for both MR and national procedures.
The procedures applied by the MHRA in assessing variations are attached here.
Guidance on appeal procedures for refused national Type II variations can be found below:
Guidance on the appeal procedure for refused national Type II variations (33Kb)
In April 2012, following consultation with medicines trade associations and member companies we announced some procedural changes concerning the requirement to submit full-colour mock-ups of labels and patient leaflets. These can be found below:
Application form
The variations application form can be downloaded from the link below:
Variations application form (external link)
Guidance on Type I notifications
The Guideline on Dossier Requirements for Type IA and IB notifications has been updated and may be found on the European Commission website (Eudralex Volume 2) (external link).
Extension applications
Information on the classification of new applications vs variation applications is provided in 'Guideline on the Categorisation of Extension Applications (EA) versus Variation Applications (V)' available on the European Commission website (Eudralex Volume 3) (external link).
Fees payable from 1 April 2012
The table on the page below provides the details of the fees payable for variation applications:
Fees for licence variations applications
Contact for further information
For further information on variations, please contact our Variations Section, 5.Y, 151 Buckingham Palace Road, London SW1W 9SZ, telephone 020 3080 7400, variationqueries@mhra.gsi.gov.uk
