Guidelines on the details of the various categories of variations Updated

The Commission has adopted the Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures ("Guidelines").  

The Guidelines replace the Guideline on the operation of the procedures laid down in Chapters II, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products as well as the Guideline on the details of the various categories of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products.

The new Guidelines reflect the changes in the procedures for the variation of the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products introduced by Commission Regulation 712/2012. The Guidelines have also been updated with new classifications to reflect adaptation to technical progress, changes introduced in the basic legislation, and the experience acquired in the application of variation classifications.

The Guidelines will also be published in the Official Journal coinciding with the entry into force on 4 August 2013 of all changes introduced in Regulation 1234/2008 by Commission Regulation 712/2012.   The purpose of the earlier publication on our website is to enable marketing authorisation holders to make the necessary preparations so that the submission of variations can be done in accordance with the procedures and classifications explained in the Guidelines by 4 August 2013.

Reference:  Guidelines on the details of the various categories of variations, on the operation of the  procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures.

Overview of New European variations system

This discussion provides a overview of the new European regulatory framework for marketing authorization variations. 

Variation is an amendment to the contents of the marketing authorization dossier 

The new Variations Regulation - Commission Regulation (EC) No 1234/2008:

• Applicable as of 1 January 2010
• Repeals Regulations 1084/2003/EC and 1085/2003/EC
• Applies to MRP, DCP and Centralsied procedures
• Does not apply to homeopathic and traditional medicinal products.

Main points of improvement:-

1. Harmonization between national competent authorities and Centralsied agency (EMA)

• Before: Two Regulations differentiating between MRP + DCP products and centrally authorised products
• The majority of variations fell outside the scope of the Community rules and were resolved nationally leading to:
• Lack of harmonisation
• Big administrative burdens for industry and national
• Now: one Regulation applying for MRP, DCP and Centralsied Procedures.

2. Simpler, clearer and more flexible classification

Variations are classified according to the level of risk to public and animal health and the impact on the quality, safety and efficacy of the medicinal product concerned into the following categories: 

• Minor variations Type IA; 
• Minor variations Type IB;
• Major variation Type II; 
• Extension of marketing authorisation.

Before: Variations conditions listed in Annex of the Regulation

Now: The Commission guideline on the details of the various categories of variations provides details for the classification of variations into the categories & possibility of scientific recommendation on classification under Art. 5(1) of the Regulation via the coordination groups (CMDh/CMDv) or the EMA

3. Do and tell procedure for Type IA variations

Type IA is a variation which has only a minimal impact, or no impact at all, on the quality, safety or efficacy of the medicinal product concerned.

Before: Tell, wait and then do procedure for Type IA ----->validation of a notification within 14 days

Now: Do and tell procedure ----------> these variations do not need prior approval

Type IA classified as:

• Type IA: Agency notified within 12 months following implementation
• Type IA IN: Agency notified immediately after implementation

4. Annual reporting

The new variations regulation introduces the possibility of annual reporting for Type I A variations not requiring immediate notification &12 months deadline to notify minor variations of Type IA allows for an ‘annual reporting’ for these variations, where a MAH submits several minor variations of Type IA which have been implemented during the previous twelve months.

5. Handling of unforeseen variations:

Before: Type II by default 

Now: Type I B by default

6. Grouping and Work-sharing

The new Regulation introduces the possibility to combine the notification of several types of notifications through Grouping and Work-sharing.

• Grouping :
• It is possible to group variations of different categories for the same marketing authorisation and submit them in one submission, under a single application form, to the same relevant authority. This is permissible where variations are covered under the cases listed in Annex III to the variations regulation. 
• For Type IA variations, it is additionally possible to group the same variation, or set of variations, in a single submission covering multiple MAs. 
• Evaluation of groups of different types of variation is conducted in line with the procedure of the highest category included within the group. For example, an extension plus a Type II variation would be assessed as an extension application, and a Type IB variation plus a Type IA variation would be assessed as a Type IB.
• Work-sharing: 
• Where an MAH may elect to submit one or more changes to several MAs under a single application. Eligible variations for initiating the procedure are Type IB or II

References:

1. Variation Guidelines
2. Regulation EC/1234/ 2008
3. European Commission Classification Guideline