Guidance

Apply to change a veterinary marketing authorisation or homeopathic remedy

Guidance on applying to vary a veterinary Marketing Authorisation (MA).

A variation is a change made to a Marketing Authorisation (MA).

Most changes require prior approval from the VMD before being made, but some do not.

A variation can be made on a national basis involving the UK only, or on a European level involving other member states.

The variation procedures apply to MAs and to registered veterinary homeopathic remedies (VHRs).

If you are unsure whether the change to be made is classed as a variation, refer to the product literature standard.

Biological products

Products containing biological active substances are known as biological veterinary medicines. A biological substance is produced or extracted from a biological source which needs, for its characterisation and determination of quality, a combination of physiochemical-biological testing together with the production process and its control.

The following are considered to be biological veterinary medicines:

  • immunological veterinary medicine which is a product administered to animals to produce active or passive immunity, or to diagnose the state of immunity to desensitise against allergens, or to produce an affect based on interaction of antigens with specific antibodies

  • veterinary medicine derived from blood and plasma

  • veterinary medicines falling within the scope of Part A of the Annex to Regulation No. 2309/93

Types of variation

There are 4 types of variation; Type IA, Type IB, Type II and Extension.

The level of complexity involved in the assessment of a variation increases from Type IA to Extension.

The list of Type IA, IB and II variations is available in the current version of the EC’s Notice to Applicants classification guideline.

The list of Extension variations is in Annex 1 of Commission Regulation 1234/2008/EC, as amended by Regulation 712/2012/EC.

Type IA

These have minimal or no impact on the safety, quality or efficacy of a product. Type IA variations are split into two sub-types:

  • Type IA - annual reports - notification of a change(s) must be made within 12 months of the change being implemented, ie. the date the Qualified Person (QP) released the first batch of product to which the change had been applied

  • Type IA IN - immediate notification - notification of a change(s) must be made immediately after the change has been implemented

Type IA variations are not assessed; they are checked to ensure:

  • correct variation type and category applied for
  • no other changes made that haven’t been applied for
  • all documentation received and accurate

These variations are charged for regardless of the outcome, ie. accepted or rejected.

The VMD will only perform a cursory check of Type IA applications where the UK is a CMS as it is the RMS’s responsibility to formally check these applications and notify the outcome to you and the CMSs involved.

Type IB

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.

Type II

This variation may have a significant impact on the safety, quality and efficacy of a product.

Extension

You apply to extend an MA to:

  • create a new stand-alone MA (new extension)
  • change an existing MA (variation extension)

You must state which you are applying for.

A new extension will be dealt with as a new MA application, ie. same procedures and timescales with a new MA granted at the end of the procedure. These may not be submitted as part of a grouped variation.

A variation extension will be dealt with the same as a new MA, ie. same procedures and timescales, but a new MA will not be granted at the end of the procedure and the existing MA will be varied.

Example

An example of an extension is the addition of a food-producing species. The original product is for use in cattle and the MA holder decides to extend this MA to include sheep; they can either apply to create a new stand-alone MA, or vary the existing MA.

If the MA holder choose to create a stand-alone MA, this will result in two products; the original product for cattle and a second product for cattle and sheep. The original product will be known as the parent product.

If the MA holder choose to vary the existing MA, this will result in one product, one for use in cattle and sheep.

New extension

These may be progressed via a national application procedure; or via the mutual recognition or decentralised procedures (MRP or DCP). For the extension to be considered under MRP or DCP, the parent product must already be mutually recognised, ie. authorised via MRP or DCP. The member state (MS) that acted as the reference member state (RMS) during the procedure to authorise the parent product will also act as the RMS during the procedure for the extension.

Variation extension

These may be progressed via national application procedures for nationally authorised products, or via DCP for mutually recognised products.

Joint-labelling

An unforeseen variation intended to achieve a single label for use in both the UK and Ireland. See the Joint labelling clarification paper page for more information.

Where a Type II or Extension variation has already been assessed for a parent product, you may apply for the same change to be made to the Copycat by submitting a variation under the relevant category, which will be dealt with as a Type IB variation. This application must be received within 2 months of completion of the parent product variation.

This only applies if no additional changes are being made to the Copycat 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 a parent product and Copycat product simultaneously by the same MA holder, a Type IB fee will apply for the Copycat variation but it will remain on a Type II timetable.

A parent MA holder has a responsibility to notify a Copycat holder when changes have been made to the parent MA. The parent MA holder should provide the Copycat holder 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.

Variations to Marketing Authorisations for Parallel Import (MAPIs)

If the SPC or product literature of the UK authorised product, ie. the parent product, is changed, you should submit a national unforeseen variation to bring the SPC and product literature of the MAPI product back into line with the parent.

Single variations

A variation application should be submitted for each change per product, ie. one change to one MA is one variation; however, there are exceptions, ie. grouped and workshare variations.

A MA may include all the different strengths and pharmaceutical forms of that product. Therefore, a single variation involves one change to one MA, or one change to several related MAs. For charging purposes this will be classed as one change to one MA.

See Related Products for more details.

All MAs included in an application must be held by the same MA holder. In the UK an MA holder 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 MA holder, you must provide justification for this with your application.

Grouped variations

These involve either more than one MA or more than one change.

All changes must be applied for on the same application form.

A grouped variation is handled in the same way as the highest ranking change involved in the application, eg. a grouped variation involving Type IB and Type II changes will be handled as a Type II variation known as a Type II Led grouped variation.

All changes included in a grouped application must apply to all the MAs included in the same application.

It is only permitted to group Type IA variations which are categorised as annual notifications with other unrelated Type IB or Type II variations.

Type IA variations which are categorised as immediate notifications 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 MAs
  • several changes to several MAs
  • several changes to one MA

The MAs do not need to be related.

Type IB, II, Extension Led

  • several changes to one MA
  • several changes to several related MAs

The MAs must be related, ie. different strengths and pharmaceutical forms of the same product. This does not apply for variations dealt with on an administrative timetable.

Applications involving Type II changes must be accompanied by an addendum to, or updating of, existing expert reports to take account of the variation(s) applied for.

Multiple application forms

A single change being made to the terms of several unrelated MAs will be applied for as separate applications (where the products are not different strengths or pharmaceutical forms of the same product). These can be considered a grouped variation for fee purposes.

Workshare variations

  • one change to several unrelated products
  • several changes to several products

The application may only include Type IB or Type II changes, or Type IA changes that are consequential to the other changes being made. 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.

UK-only workshare

A UK-only workshare application involves nationally authorised MAs in the UK. There is no involvement from other member states.

These run on a national Type II timetable.

National workshare

A national workshare application involves MAs nationally authorised in two or more member states.

These will be dealt with on a European level and run on an EU Type II timetable.

EU workshare

These will involve at least one mutually recognised product but may also involve nationally authorised products.

This type of application will be dealt with on a European level and run on an EU Type II timetable.

EMA Led workshare

These will involve at least one centrally authorised product so the application will be co-ordinated by the EMA. The application may also include mutually recognised products or nationally authorised products.

How to apply

You will find additional information about the Mutual Recognition and Decentralised procedures, including variations and renewals on the Heads of Medicines Agencies website.

You will find guidance and information about centralised procedures on the European Commission Website.

Submission

Refer to the submission guidance to submit your application electronically or in hard-copy.

If you application affects the SPC and/or QRD text, no other applications that also affect these documents should be on-going on the product when the variation is submitted. You must ensure that you time submission of applications so that they do not clash.

Application form

The application form is on the European Commission website.

Guidance on the covering letter (PDF, 21.4KB, 3 pages) .

Validation

All applications are checked (validated) upon receipt except Type IA variations.

You must identify and submit all the necessary information in support of your application. If the application is incomplete, it is likely to fail validation.

For variations involving more than one change or product the application will only pass validation once all aspects are considered acceptable.

Assessment

Once the application has passed validation, or upon receipt for Type IA variations, it will go into the assessment phase.

The timescales may be suspended if we need further information from you, or in accordance with the timetables set for applications dealt with on a European level.

If the outcome is to approve an application you will be sent authorisation documentation at the end of the application procedure.

All changes applied for must apply to all products included in a grouped or workshare variation.

You should provide the information asked for in the classification guideline or as specified for unforeseen variations.

Not all changes included in an application have to have the same outcome, ie. all approved or all refused. The outcome can be a mixture of both and you will be notified of the outcome of each change at the end of the application.

SPCs and product literature or mock-ups

See the SPCs and product literature page for more details.

Timescales

The following provides information on variation applications dealt with on a national basis only. The timescales for variations dealt with on a mutual recognition basis are outlined in the relevant Best Practice Guides, available on the CMDv website.

Type IA

Assessment Approved or refused within 30 days of receipt
Mock-ups Approved within 20 days from receipt of correct versions
Issue Following approval, updated authorisation documentation will be issued within 10 days, or 30 days for grouped variations

Type IB

Validation Validated within 10 days of receipt
Initial Assessment Approved, refused, or questions asked within 30 days of passing validation
Companse Response If questions asked, you should provide a full company response within 30 days
Sign-off Approved or refused within 30 days from receipt of a full company response
Mock-ups Approved within 20 days from receipt of correct versions
Issue Following approval, authorisation documentation will be issued within 10 days

Type II (Normal or Extended)

Validation Validated within 10 days of receipt
Initial Assessment Approved, refused, or questions asked within 60 or 90 days of validation passed
Company Response If questions asked, you should provide a full company response within 60 days. This can be extended to 120 days upon request
Sign-off Approved or refused within 60 or 90 days from receipt of a full company response
Mock-ups Approved within 20 days from receipt of correct versions
Issue Following approval, authorisation documentation will be issued within 10 days, or 30 days for workshare aoolications

Administrative Type IB Changes

Validation Validated within 10 days of receipt
Assessment Approved (including issue of authorisation documentation) or refused within 30 / 60* days of validation passed
  • An application involving 9 changes or less will be progressed within 30 days; an application involving more than 9 changes will be progressed in 60 days.

UKPAR

The UK public assessment report 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 for nationally authorised and mutually recognised products.

Fees

Once an application has passed validation, you will be sent an invoice for the fee.

For Type IA variations you will be sent an invoice for the fee following receipt of the application.

For more information see the Application fees for animal medicines page.

The VMD now issues all invoices electronically, so please provide a valid email address of where to send the invoice; failure to do so will result in your application being rejected.

The legal category may also be referred to as the distribution category.

A product may only be distributed on the market place in accordance with the distribution category shown on the product label.

Until the change in distribution category has been implemented onto the packaging of a product, you should use the product 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.

National and mutually recognised products

This will be done via a Type II variation which will be dealt with on a national basis. Please tick ‘other variation – A(z)’ in the application form.

For mutually recognised products, where changes are proposed to the product’s SPC or wording in the product literature, a variation will need to be submitted to the RMS and CMSs to obtain agreement on the proposed changes before the change in legal category can be agreed.

The assessment of the national variation to change the legal category will be suspended pending the outcome of the European variation to change the SPC or product literature.

Centralised products

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.

In the UK, prescription categories include POM-V and POM-VPS, and non-prescription categories include NFA-VPS and AVM-GSL.

Example

A change from POM-V to NFA-VPS will be dealt with by the EMA. However, if the change is from POM-V to POM-VPS (both prescription categories), or from NFA-VPS to AVM-GSL (both non-prescription categories), this would be dealt with on a national basis via a Type II variation.

If the proposed change of distribution category in the national variation results in proposed changes to the product’s SPC or wording in the product literature, a suitable variation will need to be submitted to the EMA, so that those changes may be discussed via a centralised variation procedure.

The assessment of the national variation to change the distribution category will be suspended pending the outcome of the centralised variation to change the SPC or product literature.

Referral to the Veterinary Products’ Committee (VPC)

Legal category variations will usually be considered by the 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.

Unforeseen variations

Variations not already classed as Type IA, IB, II or Extension are known as unforeseen variations and will be classed as Type IB by default.

This classification may change to Type II if the change will have significant impact on the safety, quality or efficacy of the product.

If you apply for an unforeseen variation, that has not already been considered, the VMD will refer it to the relevant European Committee, so that a decision can be made on a European level to help achieve consistency across member states.

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 as follows:

  • tick the relevant variation category
  • 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)

Dosing Instructions

When submitting a change to simple dosage instructions intended to remove ambiguity, you must provide the following:

  • confirmation that 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

When submitting a change or addition to safety warnings, you must provide the following:

  • confirmation that no other aspects of the dossier are changed, no safety warnings are removed, and 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
  • justification for the change
  • revised labels, package leaflet and SPC

Corrections to layout

When submitting normal corrections or simply text layout changes to SPC or product literature (including multilingual labelling), you must provide the following:

  • confirmation that 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 etc. are the same in all languages
  • justification for the change
  • revised labels, package leaflet and SPC

Joint-labelling

When submitting a variation to obtain joint-labels and a harmonised SPC between the UK and Ireland for nationally authorised products, or to obtain joint-labels for the first time for mutually recognised products, you must provide the following:

  • confirmation that 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 etc.
  • 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

When submitting 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) you must provide the following:

  • confirmation that the only changes are those required to bring the MAPI back in line with the parent
  • revised labels, package leaflet and SPC

Mock-Ups

When submitting mock-ups for assessment due to any of the following scenarios, please submit as a C.II.6(b) variation category NOT as a C.1.z

  • an authorised pack size not previously marketed in the UK
  • for products not marketed, which the MA holder now intends to market
  • other, eg. Where mock-ups have not been assessed

you must provide:

  • confirmation that 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

When submitting an abbreviated resubmission of a previously refused Type II variation, you must provide the following:

  • confirmation 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
  • responses to the refusal points

Advcie from the VMD

For a submission made following the formal advice of the VMD, you must provide the following:

  • confirmation 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 you failing to keep the Part II (quality) data in accordance with current practice, or in line with current CVMP guidelines
  • if required, revised labels, package leaflet and SPC

Administrative changes - A.z (Type IB)

Guidance on changes to the legal entity of an MA holder, or to distributor details

Unforeseen administrative changes include:

  • change of legal entity of MAH, eg. following a company merger or takeover
  • change of distributor, eg. addition, deletion, or changes to current distributor details

The products included in an application run on an administrative timetable do not need to be related, but they must be held by the same MA holder.

A single application can be submitted to the Veterinary Medicines Directorate for all strengths and pharmaceutical forms of one product.

The products must all contain the same active substance and belong to the same company (marketing authorisation holder (MAH)).

Mutually recognised products

Related mutually recognised products all have the same stem number which forms part of the product’s application procedure number. The procedure number stays with a product throughout its life. The procedure number is set out as follows:

  • CC/D/nnnn/sss
  • CC is the two-letter code of the Reference Member State, eg UK
  • D is either V for Veterinary, or H for Human
  • nnnn is the stem number denoting the product related to an active substance and MAH
  • sss is the speciality number denoting the strength and/or pharmaceutical form of a product.

Examples:

  • VMD 10 mg tablet for cats and small dogs UK/V/100/001
  • VMD 20 mg tablet for medium size dogs UK/V/100/002
  • VMD 30 mg tablets for large dogs UK/V/100/003

This example shows that products in the same product range, with the same active substance and belonging to the same MAH, will all have the same stem number, in this case 100. To group mutually recognised products together in a grouped variation application, all products must have the same stem number.

National Products

National products do not have procedure numbers or stem numbers. However, the same principles apply and only those products that form part of a product range and meet the criteria above may be grouped together in a grouped variation application.

If MAHs wish to group together unrelated products they may do so by submitting a workshare variation.

Copycats

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.

Type IA Changes

This advice does not apply to Type IA led grouped variations, which may include products that aren’t related.

Contact us

Published 4 June 2015
Last updated 20 April 2018 + show all updates
  1. Reviewed with amendments, including sections on SPC & Product literature and Joint-labelling
  2. Guidance reviewed with addition of timescales for mock-ups
  3. Reviewed guidance and link to SPC and product literature procedure
  4. First published.