EU Variations Guideline

Jeremy Jakob
Mar 9, 2023
2 min read

Introduction:

Edit: This guidance is still in force as of January 2023.

On 3 August 2012, the EU variation regulation 1234/2008/EC was amended by the Commission Regulation 712/2012/EC to extend the scope to all Marketing Authorizations granted in the EU, this means the inclusion of the national registered products. This inclusion will become effective as of 4 August 2013.

This guidance is still in force as of January 2023.

2. On 16 May 2013, the European Commission has published a new variation classification guideline, which became effective on 4 August 2013 and has replaced the current version.

What is new?

The Guideline has been updated with classifications to reflect adaptation to technical progress, changes introduced in the basic legislation, and the experience acquired in the application of variation classifications.

Key changes have been summarized below:

Clarification has been provided on the requirements to prove that the API manufacturing sites are appropriately authorized (see change B.I.a.1., required documentation #8)
Changes to a manufacturer of novel excipients, ASMF holder and importer have been added
More details have been provided on Design Space and Post-approval change management protocols
A new section on updates to the Adventitious Agents Safety Evaluation Information (3.2.A.2.) has been added
A replacement or addition of a manufacturing site for a pharmaceutical form manufactured by a complex manufacturing site is now classified as a Type II variation (it was previously unclassified and therefore a Type 1B unforeseen by default)
Some of the variations classified as per Article 5 have been included and in addition new variations have been added to the list of classified variations