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Variation

A variation is a change in the dossier of an authorised product. There are four different types of variations: Type IA, Type IB, Type II and Line extension.

The definitions of these variations are available in:

  • The Regulations of the European Commission: Regulation (EC) 1234/2008, Regulation (EU) 712/2012 and Delegated Regulation (EC) 11 March  2024. Last mentioned Regulation will apply as of 1 January 2025.  
  • Guidelines of the European Commission as published in Chapter 5 of Volume 2 of the Notice to Applicants.

Best Practice Guides van de CMDh with regard to variations and other procedural advice from the CMDh about the submission of variations for medicinal products with a marketing authorisation obtained via the mutual recognition or decentralised procedure can be found on the website of the CMDh. These Best Practice Guides and advice are also followed by the MEB for the submission of variations for strictly national marketing authorisations.

Specific questions relating to the method of submission of variations in the Netherlands are described in two Variations question and answer documents:

NB:

Exceptional requests for individual submission of type IA variations outside the submission of the annual update of IA variations (see CMDh BPG chapter 6) should be sent to the MEB via the email address WerkgroepVariatie@cbg-meb.nl. 

Grouped IA Variations (as of 1 January 2025)

See Chapter 6: CMDh BPG for the Processing of (Super-)Grouped Applications in the Mutual Recognition Procedure (October 2024) which kind of grouped IA variations will be possible as of 1 January 2025.

Supergrouped IA variaties -  request to NL/MEB to act as Reference Authority (RA) 

A request to NL/MEB to act as Reference Authority for a supergrouped IA variation for more than one marketing authorisation (MA) of the same Marketing Authorisation Holder (MAH) can be submitted for the following situations:

  • NL is RMS for all MAs
  • it concerns more than one MA with different RMSs
  • it concerns purely national MAs in more than one MS
  • combinations of these 3 situations

Requests as such should be sent, accompanied by a Letter of intent for the submission of a type IA grouped procedures ("Supergroup") (see CMDh website) per email to the email address WerkgroepVariatie@cbg-meb.nl. In case the MEB agrees to act as RA a procedure number will be allocated.

NB:

Requests for a procedure number for a (grouped) IA variation for more than one MA approved via MRP/DCP with NL as RMS only, which have been or will be implemented before 1 January 2025, and will be submitted before 1 January 2025, also need to be requested according to the procedure described above with a Letter of intent.

The form on the MEB website for requesting a procedure number for a (grouped) IA variation for more than one MA (Requesting a variation number for grouped applications concerning more than one MA) is not applicable anymore and has been deleted.

Worksharing of variations

Please refer to Chapter 7 of the Best Practice Guide relating to variations by the CMDh for the various options of Worksharing.

If you wish to submit a worksharing procedure with the MEB (NL) as Reference Authority (RA) for both

  • products registered via MRP/DCP with more than one reference member state (RMS) and/or exclusively applicable to strictly national marketing authorisations for the same product in several Member States
  • as exclusively products for which NL=RMS

please send a letter of intent (see CMDh website for the template) to WerkgroepVariatie@cbg-meb.nl. 

There are four different types of variations:

  • Type IA variation: a change that will have only a minimal effect or no effect at all on the quality, safety or efficacy of the relevant medicinal product and is defined in the relevant Variation Guideline of the European Commission OR is defined via an article 5 recommendation of the CMDh. A Type IA variation will only be validated and the content will not be assessed by the MEB. 
  • Type IB variation: any change that cannot be defined as Type IA variation, Type II variation or as a line extension and that will not have a significant effect on quality, safety or efficacy of the medicinal product. A type IB variation is validated and assessed.
  • Type II variation: a change that is not a so-called line extension and that could have a significant effect on the quality, safety or efficacy of the relevant medicinal product. A type II variation will be validated and assessed.
  • Line extension: an application for a marketing authorisation in the name of the same marketing authorisation holder, in which only the pharmaceutical form and/or strength differs from one or more other medicinal products for which the marketing authorisation holder already has a marketing authorisation, or has applied for such an authorisation. A line extension does not always result in a new marketing authorisation with a separate RVG number. It is also possible for an application for a line extension to result in a change of an existing marketing authorisation.