Variations

Variation files cover modifications made to marketing authorisation files. These files should be submitted to the Dispatching department (see eSubmission).

Information session 19/05/2009: presentations

National FAQ on variations

NB: On 12th December 2008 the European Commission published the Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm ). From 1st January 2010, this regulation will apply to medicinal products authorized via the centralized, decentralized and mutual recognition procedures. The FAMHP decided to extend the application of this Regulation to medicinal products authorised via the national procedure from 1st January 2010. The Royal Decree of 14th December 2006 will be amended accordingly.

A clear distinction must be made between type IA and IB variations of minor importance and type II variations of major importance.

1. Type IA and IB variations of minor importance

These changes are shown in 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 notification of the modification to the marketing authorisation must cover the points that are new compared with the current file including the amended documents in line with the modification. If the modification requires changes to the Summary of Product Characteristics (SPC), the labelling and / or the leaflet these changes are considered as an integral part of the modification.

1.1 Type IA modifications of minor importance

Examples : administrative modifications  (manufacturer’s name, holder of the marketing authorisation…), certificate up-date, minor change to a control method, …

These modifications do not require an evaluation.

Under the national procedure if no objection is received within 10 working days of receiving a valid file the modification can be applied.

Under the mutual recognition procedure the approval time is fixed by the reference member state (RMS).

The following national administrative variations are considered as type IA (article34 §1 of the Royal Decree dated 14.12.2006) : modification of the marketing authorisation holder, modification of the language area and modification of the wholesaler.

1.2 Type IB variations of minor importance

Examples : changes in the medicine’s name, the method of manufacturing the active ingredient, a new manufacturer..

These variations require an evaluation and applicants might be asked some questions.

Under the national procedure if no objection is received within 30 working days of receiving a valid file the modification can be applied.

Under the mutual recognition procedure the approval time is fixed by the reference member state.

2. Type II variations of major importance (analytical or clinical)

These are modifications that cannot be considered as modifications of minor importance or as extensions to the range.

The application to modify a marketing authorisation must include all useful information, the data justifying the requested modifications, all the modified documents and an addendum or an up-date of the expert reports, syntheses and summaries taking the requested modifications into account.

If the modification requires changes to the Summary of Product Characteristics (SPC), the labelling and / or the leaflet these changes are considered as part of the modification.

Under the national procedure a period of 60 days is foreseen to examine applications. This can be extended to 90 days for variations if it is for a change or an addition to the therapeutic indications. The period can also be prolonged 30 days if the Commission for Human Medicines considers it necessary.

Since 1/1/16 a national type II variation is invalidated if the subject is not well specified. A subject is well formulated when the reason for the variation is clear on the basis of the subject. E.g. it is inadequate to say the variation concerns an update of the CCDS. It is necessary to clarify the reason of the update.
Furthermore, we also ask to always submit a clean and annotated version of de SPC and Leaflet.
If in the SPC and Leaflet, other pending variations are repeated, you need to use a different colour per variation. It is also asked to provide a legend in the documents so it is clear which colour corresponds to which variation.

Under the mutual recognition procedure the approval time is fixed by the reference member state.

National type II variations to module 3

Clarification of the assessment strategy

Type II variations involving revision of the SPC 4.6, 5.3 and 6.6

Guidance (23/12/2011)

Clinical type II variations in the national procedure"out of scope comments" - v.2.2 (10/05/2012)

3. Readability User Testing

Since May 26, 2006, applications for marketing authorisations for medicinal products for human need to understand the evidence and the result of consultation with patient groups in terms of readability of the information (Article 6 § 1quinquies fourth paragraph of the Law on drugs). The consultation group of patients can occur in any member state and therefore also in any language. The report on the results of this consultation should be read in one of three national languages ​​or English.

For applications for MA and MAs introduced or granted before May 26, 2006, the Royal Decree of 14 December 2006 (French version) (part 1 - part 2), provides a transition period of five years to comply with these provisions.

To help the marketing authorisation holders to achieve compliance with these legal provisions, the FAMHP wrote a Q & A document (DOC, 270 Kb).

Last updated on 18/07/2017