Best practices for managing veterinary variations under Regulation (EU) 2019/6: VNRA, VRA and worksharing explained

Efficient variation management is an essential part of the lifecycle maintenance of veterinary medicinal products. While the reasons for variations remain familiar, Regulation (EU) 2019/6 has introduced procedures and requirements that call for careful planning and strategic decision-making.

After the implementation of Regulation (EU) 2019/6, practical experience and increasingly detailed guidance have provided greater clarity on how variation requirements are interpreted and applied in practice. Understanding classification principles, grouping possibilities and timelines can help marketing authorisation holders reduce administrative burden and maintain compliance throughout the product lifecycle.

This article outlines the key differences between VNRA and VRA procedures and highlights practical considerations for variation planning, grouping opportunities and efficient lifecycle management under Regulation (EU) 2019/6. For a more detailed discussion, see our webinar EU Veterinary Medicinal Products Regulation from the perspective of variations and the quality part of the pharmacovigilance system.

What is the difference between VNRA and VRA variations?

Under Regulation (EU) 2019/6, variations are divided into two categories:

• Variations not requiring assessment (VNRA)
• Variations requiring assessment (VRA)

The classification of a change determines the submission route, implementation timeline and possibilities for grouping or worksharing.

Variations not requiring assessment (VNRA)

VNRA variations follow the “do-and-tell” principle. Changes are typically implemented first and then submitted via the Union Product Database (UPD), generally within 30 days after implementation.

Examples include certain updates to pharmacovigilance information, minor changes to product information and administrative changes.

Variations requiring assessment (VRA)

VRA variations require authority approval before implementation. Depending on the variation type, different assessment timelines apply and supplementary information may be requested during the procedure.

As a result, planning and scheduling are particularly important for these changes.

VNRA versus VRA: key differences

* depending on the need for supplementary information
** VRA-R: weekly submission schedule; VRA-S/VRA-E: monthly submission schedule; advance notice is needed for VRA-S and VRA-E: 2 months and 4 months before planned submission, respectively.
*** Commission approval is expected within 1 month after adoption of the CVMP’s opinion. Linguistic review is often required for PI changes, and Commission approval in these cases takes about 1 month after the linguistic review is completed.

Because the regulatory consequences differ significantly, correct classification is the first and perhaps most important step in variation management.

If the classification of a change is unclear, early discussion with the competent authority is recommended.

Why is variation planning important?

Individual variations are often straightforward to manage. However, companies frequently face several changes simultaneously. Managing each change separately may increase workload and lead to unnecessary revisions of product information and packaging materials.

In many situations, combining and scheduling changes strategically can be more efficient than managing several sequential or parallel submissions, helping to streamline lifecycle management activities and reduce administrative burden.

Can VNRA and VRA variations be grouped together?

Direct grouping between VNRA and VRA variations is not permitted. However, grouping possibilities still exist. Variations requiring assessment can be grouped together and in those cases VRA will be processed according to the longest timetable applicable to any of the included variations. VNRA variations can be technically grouped with other VNRA changes and in some specific situations, super-grouping options are available.Understanding these possibilities early in the planning process can improve efficiency and simplify variation management.

When should worksharing be used?

Worksharing procedures apply to VRA changes when identical changes affect multiple marketing authorisations belonging to the same marketing authorisation holder. This approach is followed in order to avoid duplication of evaluation work and can significantly simplify lifecycle management of veterinary medicinal products. It will also increase the consistency across product portfolios.

Grouped variations and in certain situations, consequential variations may also be included. Because approaches may differ between national procedures and centrally authorised products, clarification with the relevant authority is recommended during the planning stage.

Is it possible to combine VNRA and VRA changes?

Although direct grouping is not allowed, alternative approaches may sometimes be available. Directly related VNRAs may be included in a VRA submission. This type of approach greatly decreases the administrative burden as there is no need to submit a separata VNRA changs via UPD in this case.

If change is not directly related, a VNRA may be upgraded to a VRA, allowing all changes to be managed within a single procedure.

Similarly, several active substance master file (ASMF) changes can sometimes be good to combine into one VRA-S variation procedure.

While these latter approaches may increase fees and extend timelines, they can reduce overall administrative burden by providing a single submission, approval and implementation date.

When can the change be implemented?

Although VNRAs are considered as “do and tell” variations, some exemptions and implementation interpretations apply. Generally, implementation is the date when the company makes the change in its own Quality System. On some occasions, this can also be a future date. For more information for CP products, see question 1 on implementation for VNRA changes, and for NP/MRP/DCP, see BPG – VNRA.

The possible implementation timeframe of a VRA can be proposed by the MAH in the application form. VRAs can be implemented only after authority approval. It is important to remember that this does not mean right after the CVMP’s opinion or EoP.

• For CP products, the VRA can be implemented depending on the VRA either after the positive CVMP opinion or after the Commission Decision has been issued and according to the time limit for the implementation set by the Commission.
• For MRP/DCP, the RMS gives a common earliest implementation date, which is 1–2 months after EoP. In case a national authority has amended the decision granting the marketing authorization before the common earliest possible implementation date, implementation is possible as soon as the amending decision is granted in a particular country.
• For NP, this varies according to national guidance.

Product information changes require careful planning

Variations affecting product information often require particular attention because they may impact printed packaging materials and involve multiple functions within the organisation. Whenever possible, combining text-related changes can help minimise the number of separate packaging updates.

Companies preparing QRD template updates should also consider timelines carefully. More practical recommendations can be found in our article on Best practices for Vet QRD template 9.1 updates.

Why is documentation critical for variation management?

Successful variation management relies on maintaining accurate records throughout the entire process. Important information to document includes:

• affected marketing authorisations;
• implementation dates;
• documentation requirements;
• grouping opportunities;
• submission references;
• authority responses;
• decisions and commitments;
• implementation timelines.

Maintaining robust records helps ensure that regulatory decisions are properly communicated and implemented throughout the organisation.

Efficient variation management requires monitoring regulatory developments and strategic planning

Practical experience with Regulation (EU) 2019/6 continues to shape regulatory expectations. Updated guidance documents, EMA questions and answers, CVMP meeting minutes and best practice guidance provide valuable insights into how authorities interpret requirements and apply them in practice. Keeping up to date with these developments helps avoid unnecessary delays and supports efficient lifecycle management.

As regulatory requirements and guidance continue to evolve, efficient variation management relies on correct classification, early planning and robust documentation. Taking a proactive approach can help reduce administrative burden, avoid unnecessary delays and support compliance throughout the lifecycle of veterinary medicinal products.

Medfiles offers reliable support for the ongoing maintenance of your marketing authorisations, whether you need full outsourcing or targeted assistance with specific tasks. We support lifecycle management activities, including variations (VRA and VNRA), preparation of Parts 2 and 1C1, ASMF updates, handling responses to authorities, MAH transfers, and the implementation of regulatory or technical changes required by authorities. Our experienced PI Team and QRD 9 experts also provide translation and product information update services.

Author:
Elina Krannila
Senior Regulatory Affairs Expert

Elina has been working at Medfiles since 2011. She is part of the Veterinary Medicines Team, where she handles regulatory tasks related to marketing authorisations (MA) of veterinary medicines. The team’s daily work includes MA applications and lifecycle management for EU veterinary products approved through centralised (CP), mutual recognition (MRP), decentralised (DCP), subsequent recognition (SRP), and national (NP) procedures. The team is well versed in veterinary legislation and relevant regulatory guidance, including the EU Veterinary Medicinal Products Regulation, UK VMD guidance, and US FDA guidance.