Variations requiring assessment

Article 62 of the Veterinary Medicinal Products Regulation provides the legal basis for a VRA.

Classification of variations requiring assessment

The Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations has an annex that outlines a classification of VRAs. The annex supplements the classifications provided in Implementing Regulation (EU) 2021/17, which describe variations not requiring assessment. The first character of the classification codes in the annex is a capital E, since these codes are a continuation of the classification codes used in the Implementing Regulation. The Implementing Regulation describes classification codes A to D.

Unclassified variations

Some variations are listed in the annex to Implementing Regulation (EU) 2021/17 but do not fulfil one or more requirements set out in that Implementing Regulation.

Or perhaps a variation does not appear in the annex to Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations.

These cases are covered under z-variations in the above-mentioned guidance document,

which provides a z-variation for each chapter. For example, the “E.z” code covers all administrative variations requiring assessment that have not yet been described. 

Timetables

VRA procedures can be subject to different timetables.

• 'R' (Reduced) indicates an abridged procedure of 30 days;
• 'S' (Standard) indicates a standard procedure of 60 days;
• 'E' (Extended) indicates an extended procedure of 90 days;
• Urgent changes: this procedure has a timetable of 22 days.

Variations with a timetable of 22 days

These are variations that are urgent in nature, for example as a result of a safety concern. In those cases, you are able to submit an application requesting an abridged procedure for urgent variations. This procedure has a timetable of 22 days.

Variations with a timetable of 30 days

The reduced timetable of 30 days can be used in less complex cases.

Variations with a timetable of 60 days

The standard timetable is 60 days and is the timetable that applies in most cases. 

Variations with a timetable of 90 days

An extended timetable (90 days) may be applied for complex variations, including fundamental changes. Fundamental changes can result in a new marketing authorisation with a separate REG NL number. This is considered an extension of a product line. The marketing authorisation holder is the same as for the other products in the same line. This is because, in effect, a new product is added to the product range offered by the marketing authorisation holder, for example by the addition of a new pharmaceutical form. 

Alternatively, a fundamental change may result in a variation to an existing marketing authorisation. In these cases, the change is implemented under the existing REG NL number.

Chapter I of the Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations outlines the variations this will apply to. The relevant variations give rise to a fundamental change in the conditions of the marketing authorisation. These changes relate to:

• The active ingredient(s);
• The strength;
• The pharmaceutical form;
• The route of administration;
• The food-producing target species.

The annex to Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations indicates the applicable timetable for each variation.

Submission of an application

To submit an VRA, you must provide all the required information to the Veterinary Medicinal Products Unit. You can read how to do this under Submission of a dossier. Please include the following documents.

Required documents

The Veterinary Medicinal Products Unit requires the following when you submit a VRA:

• A cover letter;
• A fully completed change application form;
• A description of the variation;
• Details of the marketing authorisations to which the application relates;
• For variations that result in secondary changes to the conditions of the same marketing authorisation: a description of the secondary changes concerned;
• A description of the associated VRAs and VNRAs that will be submitted during or after the VRA procedure;
• If appropriate, a copy of the CMDv/EMA opinion on the classification of the variations;
• For marketing authorisations issued under an MRP or a DCP: a list of the Member States that have issued these marketing authorisations.
• Any supporting documents required;
• Updated expert reports, if relevant;
• For variations that are the result of an earlier procedure, such as commitments and signal detection: a copy of the commitment must be included along with the documentation.
• The required details for the variation. These are listed in Article 8 of the Veterinary Medicinal Products Regulation. Detailed descriptions of the dossier requirements can be found in the Guidance on the details of the classification of variations requiring assessment according to Article 62 of Regulation (EU) 2019/6 for veterinary medicinal products and on the documentation to be submitted pursuant to those variations;
• For variations that give rise to changes in the Summary of Product Characteristics, labelling or package leaflet: the relevant changes form part of the variation;
• If applicable an SPC, labelling, package leaflet proposal in WORD. The electronic SPC, labelling and package leaflet must be prepared according to the established template. For information on how to complete the SPC, labelling and package leaflet, please see the CMDv guidance documents relating to the SPC, labelling and package leaflet.

Application procedures

You can use the following application procedures to submit a VRA:

• National procedure;
• Mutual recognition or decentralised procedure (MRP/DCP);
• Centralised procedure.

National procedure

If a veterinary medicinal procedure was granted marketing authorisation in the Netherlands via the national procedure, the variation will be approved or rejected by the Veterinary Medicinal Products Unit. This unit will also enter the information in the UPD. In this case, the Veterinary Medicinal Products Unit is the competent authority.

MRP/DCP

If a veterinary medicinal procedure was granted marketing authorisation via an MRP or a DCP, the variation will be approved or rejected by the Reference Member State (RMS). This Member State will also enter the information in the UPD. In this case, the RMS is the competent authority.

An MRP or a DCP involves a Reference Member State (RMS), with which you will have to coordinate the change first. If the RMS is the Netherlands, our advice is that you contact the Veterinary Medicinal Products Unit before you submit the variation. This is so the variation can be discussed beforehand.

The change is submitted to the RMS and all Concerned Member States (CMS) simultaneously. After completion the member states involved will implement the decision in their national marketing authorisation. This also includes the implementation of the definitively approved translations of the SPC, labelling and the package leaflet in the national marketing authorisation.

A CMS must include the definitively approved translations of the SPC, labelling and the package leaflet in the national marketing authorisation within 3 months.

Centralised procedure

If a veterinary medicinal procedure was granted marketing authorisation via the centralised procedure, the variation will be approved or rejected by the European Commission. The Commission will also enter the information in the UPD. In this case, the Commission is the competent authority.

For more information about variations, see Variations on the EMA website.

Approval of variations

When the variation is approved, the competent authority will determine the definitely improved SPC, labelling and package leaflet. 

You will be able to implement the changes once the requested variation to the marketing authorisation has been processed.

Rejection of variations

The competent authority will inform you that the variation has been rejected. You will not be able to implement the variation in the marketing authorisation. You have the option to submit the variation again at a later time, with revised documentation.

More information

Further information is available in the Best Practice Guide for variations requiring assessment. If you have any further questions about VRA, please contact the Veterinary Medicinal Products Unit. 

Important note: The VRA procedure based on the Veterinary Medicinal Products Regulation is a new procedure. Expectations are that the procedures will be clarified further in the period ahead and that Best Practice Guides will be supplemented or amended. The above text will be updated as soon as any developments take place.