Guidance for the pharmaceutical industry on how to apply to vary a veterinary Marketing Authorisation (MA) or Homeopathic Remedy.
Most changes to a Marketing Authorisation (MA) or Veterinary Homeopathic Registration (VHR) require prior approval from the VMD before being made, but some changes can be made with retrospective applications. If you are unsure if your proposed change requires a variation, contact us at email@example.com.
Types of variation
There are 4 types of variation which increase in assessment complexity.
These have little or no impact on the safety, quality or efficacy of a product. Type IA variations are split into 2 sub-types:
- Type IA (annual updates) – You must notify us of the change(s) within 12 months of the date the Qualified Person (QP) released the first batch of product to which the change had been applied
- Type IA (immediate notification) - You must notify us of a change immediately after the change has been applied
These applications are checked to ensure that:
- the correct variation type and category has been selected
- no other changes have been made that haven’t been applied for
- all documentation has been received and is accurate
If the application is rejected the fee is still charged.
It is worth noting that:
- annual updates should not be submitted if one or more of the products involved are undergoing another procedure, such as another variation or renewal
- annual notification changes can be submitted with other unrelated Type IB or Type II changes
- immediate notification changes can only be submitted with other Type IB or Type II changes that fall within the grouping as per Annex III of the variation regulations
A variation is Type IB by default if it is not Type IA, Type II or an Extension. A list of some changes that are classified as Type IB can be found in the classification guideline.
These changes may have a significant impact on the safety, quality and efficacy of a product. Applications involving Type II changes must include an addendum to, or updating of, existing expert reports to take account of the variation(s) applied for.
You apply to extend an MA to either:
- create a new stand-alone MA (new extension) using the same procedures and timescales for a new MA – These can’t be submitted as part of a grouped variation. At the end of the procedure a new MA is granted resulting in 2 products; the original unchanged product (known as the parent) and the newly extended product.
- change an existing MA (variation extension) also using the same procedures and timescales for a new MA, but a new MA is not granted at the end of the procedure. Here the existing MA will be varied to include the extension.
You must state in your application which you are applying for.
The list of Type IA, Type IB and Type II variations is available in the EC’s Notice to Applicants classification guideline and those for Extension variations is in Annex 1 of Commission Regulation 1234/2008/EC, as amended by Regulation 712/2012/EC.
Variations not already classified are known as Unforeseen Variations. These should be applied for as Type IB, however, we may change this to Type II if the change has significant impact on the safety, quality or efficacy of the product. Previous Unforeseen Variations are listed in the section Unforeseen Variations for information, below.
SPCs and product literature or mock-ups
See the SPCs and product literature page for more details.
One variation application can be submitted to cover one change to one product but can also be used for one change to a product range, known as related. This does not apply to grouped and workshare variations.
A single application can be submitted for all strengths and pharmaceutical forms of one product, a so-called ‘product range’.
The products must all contain the same active substance and belong to the same MAH. In the UK an MAH is identifiable by their unique company number, which forms the first part of a product’s Vm number. If the products submitted as part of a group or workshare variation have different company numbers, but you believe them to belong to the same MAH, you must provide justification for this with your application. An example of a product range is as follows:
- Product Name 10 mg tablet for cats and small dogs
- Product Name 20 mg tablet for medium size dogs
- Product Name 30 mg tablets for large dogs
Products authorised under a different legal basis such as Informed consent (copycats) are not considered to be related to the parent product for the purpose of grouped variations. This is also true where there might be multiple informed consent marketing authorisations (MAs) derived from the same parent product, these multiple copycats cannot be grouped. The same restriction applies to generic products and parallel imports which are all stand-alone MAs in their own right.
Grouped variations can include more than one product or more than one change but these must be applied for on the same application form and must apply to all included products.
These are handled using the process and timetable for the highest complexity classification, for example, a grouped variation involving Type IB and Type II changes will be processed as Type II Led.
It is only permitted to group Type IA (annual update) variations with other unrelated Type IB or Type II variations. Type IA (immediate notification) variations can only be grouped with other Type IB or Type II variations if the grouping falls within one of the categories listed in Annex III of Variation Regulation 1234/2008.
Type IA Led:
- one change to several products
- several changes to several products
- several changes to one product
The products don’t need to be related, for example, they don’t need to be part of a product range.
Type IB, II, Extension Led:
- several changes to one product
- several changes to several related products part of a product range
The MAs do not need to be related when included in a variation dealt with on an administrative timetable
Multiple application forms
A single change being made to the terms of several unrelated MAs must be submitted as separate applications, however, these can be considered a grouped variation for fee purposes.
Variations to parent products
Informed consent (copycats)
Where a Type II or Extension variation has already been authorised for a parent product, you may apply for the same change to be made to the copycat within 2 months of its completion.
Using the relevant category, these will be dealt with as a Type IB if no additional changes are added and no additional data needs to be assessed. If any data is submitted a full Type II fee and timetable will apply.
Where a Type II or Extension variation is submitted for both the parent and copycat products simultaneously by the same MA holder, a Type IB fee will apply for the copycat variation but a Type II timetable will apply.
A parent MA holder has a responsibility to notify a copycat holder when changes have been made and should provide them with at least the categories used for the variation(s) and, ideally, the application number. The copycat holder needs this information to apply for the same changes.
Marketing Authorisations for Parallel Import (MAPIs)
If the SPC or product literature of the UK authorised parent product is changed, you must submit a national Unforeseen Variation to align the MAPI product.
Workshare variations for national only MAs
- one change to several unrelated products
- several changes to several unrelated products
Only national GB and NI MA products can be included in a workshare application and can only include Type IB or Type II changes, or Type IA changes that are consequential to the other changes being made. These products don’t need to be related.
A workshare application cannot include an Extension variation.
These will run on a Type II timetable regardless of the types of changes included in the application.
Change of legal category
The legal category may also be referred to as the distribution category.
A product may only be distributed on the marketplace in accordance with the distribution category shown on the product label. Therefore, until the change in distribution category has been implemented onto the packaging of a product, it must continue to the distributed in accordance with the distribution category shown on the product label.
For further information about distribution categories see the guidance on Retail of veterinary medicines . When applying for a legal category change, select ‘other variation – A(z)’ in the application form. This change will be dealt with as a Type II variation.
Legal category variations will usually be considered by the Veterinary Products Committee (VPC) unless the VPC has already provided advice on the appropriate legal category of products containing the same active ingredient(s) and indicated for use in the same target species.
UK Wide MAs where NI is CMS
For UK wide MAs where NI is CMS which include proposed changes to the SPC or wording in the product literature, a variation will need to be submitted in parallel to the RMS, other CMSs and to the VMD. You only need to submit the application to us once to cover both NI as CMS and the GB element to your UK wide MA.
A change to the legal category from prescription to non-prescription (or vice versa) will be dealt with by the EMA via a centralised variation procedure.
A number of unforeseen variations have already been considered and these are listed below. These variations are dealt with on a national basis regardless of whether the MA is nationally authorised or mutually recognised.
You should complete the application form by selecting the relevant variation category given here, and include a clear, concise description of the variation under ‘scope of change’ in the present and proposed sections.
SPC or Product literature changes - C.I.z (Type IB)
|Change||Description||Confirmation/Justification (must be provided)||Packaging to be provided|
|Dosing Instructions||changes to simple dosage instructions intended to remove ambiguity||the change is not the result of safety concerns, no new studies are required to support the change and the dosing regimen remains the same|
|Safety Warnings||change or addition to safety warnings||no other aspects of the dossier are changed, no safety warnings are removed, no new studies are required to support the change and the proposed warnings serve to increase the protection of the user, the environment or target species. As appropriate justify the change||revised labels, package leaflet and SPC|
|Corrections to layout||normal corrections or simple text layout changes to SPC or product literature (including multilingual labelling)||no other aspects of the dossier are changed, the changes are not the result of any safety concerns, the legibility is not compromised and the indications or warnings are the same in all languages; justify the change||revised labels, package leaflet and SPC|
|Joint-labelling||to obtain joint-labels between the UK and Ireland for nationally authorised products or to obtain joint-labels for the first time for mutually recognised products||no other aspects of the dossier are changed, the changes are not the result of any safety concerns, the legibility is not compromised and the indications or warnings are the same in all languages||revised labels, package leaflet and SPC current SPCs for the UK and Ireland and a proposed joint SPC - only applicable for joint-labelling variations on nationally authorised products|
|Changes to MAPIs||changes to the SPC and product literature of a MAPI as a direct consequence of a change to the SPC and product literature of the UK authorised product (parent)||the only changes are those required to bring the MAPI back in line with the parent||revised labels, package leaflet and SPC|
|Mock-Ups||mock-ups for assessment due to any of the following scenarios must be submitted as a C.II.6(b) variation category NOT as a C.1.z: authorised pack size not previously marketed in the UK, products not marketed, which the MA holder now intends to market and where mock-ups have not been assessed||the pack size(s) are already authorised and no new studies are required to support the change and no other aspects of the dossier have changed||mock-ups for the relevant pack size(s) and an updated package leaflet if applicable|
Miscellaneous changes - C.II.z (Type IB)
Resubmission of Type II Variations are an abbreviated resubmission of a previously refused Type II variation, you must:
- confirm that at the time of refusal the VMD gave you permission to resubmit under this category, and that the application has been resubmitted within 3 months from the date the previous application was refused
- provide responses to the refusal points
Following formal advice of the VMD, you must:
- confirm that the VMD has already assessed the relevant data and formed an opinion on these, and that the change is not required as a result of your failing to keep the Part II (quality) data in accordance with current practice, or in line with current CVMP guidelines
- if required, provide revised labels, package leaflet and SPC
Miscellaneous changes - split of a UK wide MA
Whilst the UK and EU operate an equivalent regulatory framework, opinions align, and you do not introduce divergence to the MA, you will be able to maintain your existing MAs which are valid UK wide. This also includes continued alignment of the data package, Summary or Product Characteristics and labelling.
If the Regulations diverge, it may be necessary to separate these MAs to allow for regulatory differences. This would mean you would have 1 MA valid in GB, subject to UK Regulations and 1 MA valid in NI, subject to EU Regulations.
If the UK and EU opinions are not aligned it may not be possible to maintain an MA valid UK wide. Depending on the reason for difference in opinion, you may be able to separate the MA to 1 MA valid in GB, subject to UK Regulations and opinion, and 1 MA valid in NI, subject to EU Regulations and opinion.
This means that if the UK opinion is not favourable contrary to the EU, it may not be possible for the MA to remain valid in GB. Equally if the UK opinion is favourable contrary to the EU it may be possible for the MA to remain valid in GB only.
Introducing divergence to an MA
To maintain alignment of your UK wide MAs authorised via MRP or DCP procedures, you must submit post authorisation applications to both the EU and the VMD for assessment at the same time. By not submitting applications to either authority will introduce divergence and your MA may be separated into 1 MA valid in GB, subject to UK Regulations and 1 MA valid in NI, subject to EU Regulations.
National only UK wide MA
Unless it is your intention to do so, you must ensure that variations do not introduce changes that contravene either UK or EU regulations, as this may result in MA separation.
Upon separation, your new GB and NI MAs will be issued with a new Vm number for each, which will mean necessary changes to product literature and packaging.
Originally authorised via MRP and DCP
To maintain a UK wide MA, you must ensure that variations are submitted under both GB and EU routes at the same time in order to retain alignment. However, changes which may occur during the respective assessment by the GB and EU authorities could introduce changes that either contravene UK or EU regulations or change the terms of authorisation valid in GB and NI, which may result in MA separation.
See Submission of an application for an animal medicine authorisation for further information. Failure to submit a duplicate application to either us or the EU could result in MA separation.
Upon separation, your new GB and NI MAs will be issued with a new Vm number for each, which will mean necessary changes to product literature and packaging.
If you want to split a UK wide MA (4xxx Vm number) to GB (5xxx) and NI (3xxx) MAs and there are no other changes to the dossier:
- Select category A(z) Other Variation (Type IB)
- Do not submit revised SPC, QRD text or mock-ups for administrative changes. We will annotate the agreed changes onto the latest authorised versions held on file and issue them back to you at the end of the variation procedure
Administrative changes - A.z (Type IB)
See MAHs, Named Distributors and Local Representatives of veterinary medicines for guidance on how to make changes.
Before submitting your application
You must be registered to use the Veterinary Medicines Digital Service (VMDS).
If your application affects the SPC and/or QRD text, no other applications that also affect these documents should be ongoing on the product when the variation is submitted. You must ensure that you time submission of applications so that they do not clash.
You can submit variation applications in parallel to coordinate identical proposed changes to GB MAs with NI national, mutually recognised and centralised MAs (including maintaining alignment between the GB and NI parts of a UK wide MA, where NI is a CMS) to allow for efficient application management, providing the opportunity for multiple applications to be managed within similar timeframes across regulatory jurisdictions.
If applicable, you must submit your applications to the EU and then, within 2 working days at the latest, submit the GB applications to the VMD via the VMDS. As confirmation, you must include the date you submitted your application and any EU reference numbers, if you have them, in the comments box in the VMDS online form.
Applications must also be for the same product, meaning they:
- are the same pharmaceutical form *have the same qualitative and quantitative composition
- are intended for the same target species with the same indications
- have the same dossier. Except for certain differences that make no impact on the scientific requirements or regulatory framework such as sites of batch release
Where a parallel submission involves an EU procedure, as the procedure progresses, it is your responsibility to ensure we are aware of information and timetables (including timetable amendments) that you wish to be considered during our assessment. You may also need to provide us with EU Lists of Questions (LOQs) and your responses in order to maximise the potential for harmonised labelling.
It is not possible to parallel assess between an EU procedure and a nationally authorised UK wide MA; these applications will follow the national timetables. See Timetables for national applications.
Where a parallel submission is purely national, the application will follow the national timetables. See Timetables for national applications.
Applications and responses must be submitted electronically and the presentation and format of the dossier must be in accordance with VNeeS guidelines.
You must prove technical validity before submission of the electronic dossier and should include the validation report in the add-info folder of the VNeeS submission.
Application forms to apply for a national variation are now online through the VMDS. You will be asked whether the application is for GB, NI or both.
European procedure application forms are available on the European Commission website.
How to submit your application
See Submission of applications to an animal medicines for guidance.
Active Substance Master Files and responses to questions in relation to applications, should be submitted via the same method as the application.
Most applications are validated upon receipt to check that everything has been provided in order to begin the assessment.
It is up to you to identify and submit all the necessary information in support of your application. If the submission is incomplete, we may not be able to progress your application. For variations involving more than one change or product the application will only pass validation once all aspects are considered acceptable.
We will contact you if further information is needed.
Once an application has passed validation, or upon receipt for applications that do not have a validation period, you will be sent an invoice for the fee by email so you must provide a valid email address in your application.
Once the application has passed validation, or upon receipt for applications that do not have a validation period, it will go into the assessment phase. See Timetables for national applications. If you have requested parallel assessment with an EU application, these timetables will not apply.
You will receive our questions and our decision whether to approve or refuse around the same time as the corresponding EU procedure.
If during the assessment phase we need further information from you, our timescales may be suspended until the information is received.
If the assessment outcome is to approve an application and where applicable we have approved mock-ups, we will email your authorisation documentation. It is possible that not all changes included in an application have the same outcome and can be a mixture of approved and refused. You will be notified of the outcome of each change at the end of the application.
UK Public Assessment Report
From 1 January 2021, some products that were originally authorised via EU procedures may not have a UK Public Assessment Report (UKPAR) available. We will endeavour to populate this information over time. The UKPAR will be updated following a major change to the product.
The post authorisation assessment (PAA) document will be updated following successful completion of all variations on nationally authorised and mutually recognised products. Details of post authorisation activities on Centrally authorised products will be published by the EMA.
- To request a company meeting prior to applying email: firstname.lastname@example.org and include ‘Request a company meeting’ in the subject line
- Once you have applied, to discuss specific application points contact the people assigned to the application given in the validation passed email
- for all other enquiries email: email@example.com