After a medicinal product has been authorised, the terms of the marketing authorisation may subsequently be varied. Variation notifications, for example addition of a new manufacturing site or a new indication, are defined in Commission Regulation (EC) 1084/2003 as either ‘minor’ (Type I) variations or ‘major’ (type II) variations.
New Variations Regulation - Key points to note
The new ‘Variations Regulation’ (Commission Regulation 1234/2008) came into force on 1st January 2010 and applies immediately to human and veterinary medicinal products authorised through the centralised and MRP/DCP routes. The applicability of this regulation will be formally extended to ‘purely National’ marketing authorisations at a later date. However, in line with many other European regulatory agencies, the IMB has taken the decision to implement the general principles of the new Regulation to all marketing authorisations from 1st January 2010. It is felt that having a single set of rules and procedures will simplify operation of the new regulation for both MA holders and the IMB.
For more information on the new variations regulation and how the IMB will implement it, refer to the following document:
New Variations Regulation - key points to note
MAH’s need to consider the possible need to notify Healthcare Professionals when implementing Type IA Variations. Click here to read more.
For a medicinal product which was authorised via a National procedure, all variation applications are made directly to the IMB. Where a product has been authorised through the Mutual Recognition or Decentralised procedure, applications should be made to the Reference Member State (RMS) for that product.
For further information on variations, a list of links to published documents relating to the new variations regulation, please click here.
Variation applications for both national and mutual recognition procedures (Type 1A, 1B and Type II) are made using the EU ‘Application for Variation to a Marketing Authorisation’ form. This form is available on the ‘Publications’ page of the IMB website.
All National and Mutual Recognition/Decentralised variations are approved by letter, with the exception of Mutual Recognition Type I variations, for which the applicant receives notification from the RMS. If the variation involves a change to the product authorisation schedule, an updated schedule will be sent to the applicant following approval of the application. For products authorised by the European Commission (centralised procedure), variation applications should be submitted to the EMEA. For more information, please consult the EMEA website, www.ema.europa.eu
The new variation application form has been published on the European Commission website and must be used from 1 January 2010 for all marketing authorisation variations submissions.
Application for variation to a marketing authorisation.
A user guide on how to use the new variation application form has also been published by the European Medicines Agency and CMDh.
Explanatory notes on Variation Application Form (Human medicinal products only) (January 2010)
Notifications for changes to the label and leaflet which do not affect the Summary of Product Characteristics (notifications under Article 61(3) of European Commission Directive 2001/83/EC)
Article 61(3) of Directive 2001/83/EC as amended relates to a provision to amend the labelling or package leaflet of a marketing authorisation in respect of aspects not connected to the SPC. Following implementation of the new pharmaceutical legislation in October 2005 this applies to the harmonised label and package leaflet resulting from DCP / MR procedures. For DCP /MR approved products, the scope of the provision extends to those European aspects of the label and PL where a harmonised position has previously been reached and is to be maintained.
Further guidance on this procedure is available from the CMD(h) Standard Operating Procedure - Procedure For Article 61(3) Changes To Patient Information
There is an exception where the labels and leaflets are not harmonised or where changes to information have been agreed on a national basis. These changes can be submitted nationally. Separate application forms are required for notifications under the Article 61(3) procedure, as referred to above. Both the national form and the EU form are available on the ‘Publications’ page of the IMB website.