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 en Regulation (EU) 712/2012
  • 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:

Grouped applications

The following grouped variations are possible:

  • Grouped applications of more than one variation for one marketing authorisation
  • Grouped variations of (more than) one type IA variation(s) for several marketing authorisations; including so-called “supergrouped” type IA variation(s) for more than one marketing authorisation
  • So-called horizontal grouping of variations: relating to one or more variation(s) that all apply to several strictly national marketing authorisations (a separate procedure number is not required for this).

When applying for a variation number for a grouped type IA variation(s) for more than one marketing authorisation (obtained via MRP or DCP), please use the application form for requesting this variation number.

When applying for a supergrouped type IA variation with the MEB (NL) as lead Member State, please send a letter of intent via e-mail to Mrs Kora Doorduyn-van der Stoep using the e-mail address WerkgroepVariatie@cbg-meb.nl. For these supergrouped variations, you should not submit a separate request for a procedure number via the above-mentioned form on the MEB website.

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 to Mrs. Kora Doorduyn-van der Stoep using the e-mail address 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. The applicant will receive a confirmation of receipt of a valid application for products registered via a national procedure, as well as for products registered via MRP/DCP if NL is RMS.
  • 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 (change of the RVG number).