Q&A: Type II variations vs Extension applications

The Variations Regulation defines a Type II variation as a major variation which may have a significant impact on the quality, safety or efficacy of a medicinal product.

The Variations Regulation and the Variations Guidelines set out a list of changes to be considered as Type II variations. In addition, any other change which may have a significant impact on the quality, safety or efficacy of the medicinal product must be submitted as a Type II variation.

Certain changes to a marketing authorisation, however, have to be considered to fundamentally alter the terms of this authorisation and therefore cannot be granted following a variation procedure. These changes are to be submitted as ‘Extensions of a marketing authorisation’ and are listed in Annex I of the Variations Regulation.

This Annex lists three main categories of changes requiring an extension of marketing authorisation:

• changes to the active substances;
• changes to strength, pharmaceutical form and route of administration;
• change or addition of food-producing target species.

The European Commission has published a guideline to clarify the terms ‘pharmaceutical form’ and ‘strength’, including relevant examples for such classification: Guideline on the categorisation of extension applications (EA) versus variations applications (V) - October 2003.

This guideline on categorisation should be read in conjunction with the Variations Regulation and the European Directorate for the Quality of Medicines and Healthcare (EDQM) guidance on Standard terms: Introduction and guidance for use, and should be understood as follows:

Changes to a centralised marketing authorisation listed below should be submitted as variations according to the guideline on the details of the various categories of variations to the terms of marketing authorisations:

• • addition or replacement of a presentation for a solution for injection with a different immediate container (e.g. vial, syringe, prefilled pen, cartridge or ampoule);
  • addition or replacement of a presentation for an eye-drop solution with a different immediate container.

In case of doubt, the MAH is advised to contact vet.applications@ema.europa.eu in advance of the submission.

References

• Commission Regulation (EC) No 1234/2008
• Commission Regulation (EU) No 712/2012 amending Regulation (EC) No 1234/2008
• Variations Guidelines (2013/C 223/01)
• Guideline on the categorisation of extension applications (EA) versus variations applications (V) - October 2003”, The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 6C
• EDQM guidance on Standard terms: Introduction and guidance for use