Guidance for the pharmaceutical industry on applying for a marketing authorisation.
You need a marketing authorisation (MA) to place a veterinary medicine on the market for sale and supply.
- some animal medicines do not need an MA, read the Exemption from authorisation for medicines for small pet animals page, and
- some products are not considered animal medicines, read the Legal controls on veterinary medicines page
If your product is a veterinary medicine and does require an MA, you need to submit an application to the VMD.
The Marketing Authorisation Holder (MAH) of the product must:
- be established within the Community. See Marketing Authorisation Holders, Named Distributors, and Local Representatives of veterinary medicines.
The Vm symbol
An authorised product will have an authorisation number preceded by the symbol Vm on its product literature, e.g. labels. This offers users a clear guarantee that the product has been assessed and approved in accordance with the instructions on the product literature.
A product subject to an MA issued by the European Commission (EC) will not have the Vm symbol on its product literature; instead an identifier with the following format will be used - EU/2/01/011/001.
Products tend to be classed as pharmaceutical or biological.
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
There are four routes that can be used to get an MA:
- Mutual Recognition
These routes determine the procedures, processes and timelines used in processing an application for a new MA. Once granted, the authorisation will be nationally authorised, centrally authorised, or mutually recognised.
Nationally authorised products
A product that has been assessed and approved on a national basis only, i.e. there has been no interaction with other EU MSs.
Centrally authorised products
A centrally authorised product is one that has been assessed and approved on a community level involving all EU MSs. A pan-European authorisation is issued by the European Commission (EC) permitting the marketing, sale and supply of the product in all EU MSs including the UK.
The European Medicines Agency (EMA) organises the process of evaluation using scientific expertise from all EU MSs. If a positive opinion is given by the EMA after a product has been evaluated, it is sent to the EC. If the EC also has a favourable opinion, it makes a formal decision to authorise the product and it grants a single MA that is valid in all EU MSs. Note, whilst the EC will usually endorse a positive opinion, it has the right to reject it.
Although the VMD does not issue an MA for products authorised by the centralised procedure, the outcome is the same: the product is authorised for use in the UK.
The centralised procedure is compulsory for some products and optional for others. some products are not eligible for the centralised procedure.
Mutually recognised products
A mutually recognised product is one that has been assessed and approved on a European level involving at least two EU MSs, i.e. evaluated via the mutual recognition or decentralised procedure.
The mutual recognition procedure (MRP) is a European authorisation route resulting in a mutually recognised product.
Mutual recognition must be used when a product is already authorised in at least one EU MS on a national basis and the MAH wishes to obtain an MA for the same product in at least in one other EU MS.
The MS that has already authorised the product is known as the Reference MS (RMS). The RMS submits their evaluation of the product to the other MSs; known as a Concerned MSs (CMS). The CMS is asked to mutually recognise the MA of the RMS.
If the application is successful, the CMS will then issue an MA for that product permitting the marketing of that product in their country. Please note if the UK acts as RMS this means the product was initially authorised in the UK on a national basis; therefore, once the MRP has been successfully completed, the authorisation type of the UK MA will change from ‘National’ to ‘Mutually Recognised’.
The decentralised procedure (DCP) is a European authorisation route resulting in a mutually recognised product.
The difference between MRP and DCP is that a product must already be authorised in at least one MS on a national basis in order for MRP to be used. DCP may be used if the product is not authorised in any EU MS and a company wishes to authorise it in several or all EU MSs, but only if the centralised procedure is not mandatory, or the company does not wish to use the centralised procedure (where it is optional), or the product is not eligible for the centralised procedure.
One of the proposed MSs will be asked by the MAH to act as the RMS. The RMS does the initial evaluation of the product and issues a draft assessment report including a list of unresolved issued. The CMS either agree with the RMS’s evaluation or they ask further questions/raise objections.
If all the issues are resolved and the application is successful, each MS will then issue an MA for that product permitting it to be marketed in their country.
There are several different legal bases upon which an application for an MA may be applied for; these reflect the type and content of the data submitted in support of the application.
All references refer to Directive 2001/82/EC, as amended by 2004/28/EC.
- Article 12(3) - based on a full dossier using the MAH’s own propriety data, or
a mixture of their own data and some bibliography
- Article 13 - generics
- Article 13(3) - generic hybrids
- Article 13(a) - bibliographic (well-established use)
- Article 13 (b) - fixed combination
- Article 13(c) - Informed consent
- Article 13 (d) - biosimiliars
You may also apply to extend an existing MA to create a new stand-alone MA.
The data and documents required in support of an application for an MA are set out in Volumes 6a and 6b of the European Notice to Applicants and in Annex I to Directive 2001/82/EC, as amended.
You may also apply for the following types of MA:
Exceptional MAs – provisional or limited
Marketing Authorisation for Parallel Import (MAPI); further information
The data and documents required to support an application for an exceptional MA or MAPI are provided in the application forms.
You may apply for a generic MA by referring to the safety and efficacy aspects of a data package submitted in support of an already authorised veterinary medicine, which is referred to as the reference product.
In addition to a full quality data package, you would need to provide an environmental risk assessment for the product and a user risk assessment. The type of user risk assessment provided depends on the degree of similarity between the generic and reference products.
For generics of injectable products the submission of injection site residues data are necessary, unless a biowaiver exempts the application from the need for residues studies.
You must demonstrate that the generic product is bioequivalent to the reference product, unless an exemption from demonstrating bioequivalence applies. The reference product must have been authorised for at least 10 years before the generic product can be placed on the market. For applications for generic products, which are based on reference products authorised after October 2005, the application can be submitted after eight years of authorisation, but the generic product cannot be marketed until the 10 year data protection period has expired.
In some cases the data protection period for the reference product may be extended to 13 years. For products indicated for the treatment of bees and fish the protection period of the reference product is automatically 13 years.
The SPC of the generic product should follow the SPC of the reference product.
Generics of biological products are not possible unless the Master Seed and production process are the same.
Reference product - the reference product must be authorised in accordance with any of the following articles: 12(3), 13(a), 13(b), 13(c) or 13(d), ie. you cannot use a product authorised in accordance with article 13 (generic) or 13(3) (generic-hybrid), a MAPI, or exceptional MA as a reference product.
A hybrid MA follows the same principles as those for generic applications, but such applications are required under the following two scenarios:
- if you are not able to demonstrate bioequivalence to the reference product through bioavailability studies
- where bioequivalence can be demonstrated to the reference product, but you want to make changes, eg. in the active substance(s), or changes to the therapeutic indications, strength or pharmaceutical form or to the route of administration
Example of a hybrid MA: The reference product is indicated for use in cats and dogs and is administered orally. You want your product to include cats and dogs, but want an injectable product. You refer to the reference product to cover some of the safety and efficacy data requirements, but produce your own data to support the change in the route of administration.
A bibliographic MA is based on an application where all parts of the data dossier are addressed using bibliography, i.e. published data. This type of MA may also be referred to as an MA based on well-established use. You must demonstrate the active substance has been used for at least ten years in the target species for the indications applied for.
An application for a product containing active substances already used in an authorised product, but not previously used in that combination in an authorised product. In this case, you don’t need to provide safety and efficacy data for the individual active substances.
Informed Consent (Copycats)
One of the most common types of MA is the ‘copycat’; this is an informal term used to describe an MA authorised on the basis of informed consent. In such cases, you cross-refer to specific parts of the data package for an already authorised veterinary medicine, which is referred to as the parent product. For these applications, only a full Part I of the dossier needs to be submitted (including European tables of materials of human and animal origin).
Apart from the product name, the product’s authorisation number and, possibly, the MAH and pharmacovigilance systems (DDPS), all of the details of the proposed copycat are identical to the parent.
For a product to be authorised on the basis of informed consent, the MAH for the parent product must have given the VMD permission to refer to the data submitted in support of the parent product.
If the MAH of the parent product is different from the MAH of the proposed copycat, a formal letter of access from the parent MAH is required; this should be submitted as part of the application package submitted in support of the copycat. If the MAH of the parent and copycat products are the same, a formal letter of access is not required.
A parent MAH has a responsibility to notify a copycat holder when changes have been made to the parent MA. The parent MAH 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 in order to apply for the same changes.
Parent product – the parent product must be authorised in accordance with any of the following articles: 12(3), 13(a), 13(b), or 13(d), ie. you cannot use a product authorised in accordance with article 13 (generic), 13(3) (generic-hybrid), 13(c) (informed consent), a MAPI, or exceptional MA as a parent product.
Where a biological product, which is similar to a reference biological product, does not meet the conditions in the definition of a generic product, owing to, in particular, differences relating to raw materials or in a manufacturing processes of the biological product and the reference biological product, the results of appropriate pre-clinical tests or clinical tests relating to these conditions must be provided.
An extension is a type of variation. The MAH may extend an existing MA to:
- create a new stand-alone MA (new extension)
- change an existing MA (variation extension)
Upon submission of an application you must state whether you are applying for a new extension or variation extension.
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.
An exceptional MA may be granted following submission of a reduced data package where specific data has been omitted.
There are 2 types of exceptional MA; provisional and limited.
You may apply for a provisional MA (PMA) when there is no fully authorised product available in the UK to prevent or treat a particular condition.
A PMA is normally granted to help address an urgent situation, e.g. as a result of a new disease. PMAs are intended to exist in the short term whilst you generate data to support a full MA.
You may apply for a limited MA (LMA) to help fill an existing therapeutic gap and where the product is not expected to be sold in vast quantities; therefore, it is unrealistic to expect you to generate full data packages and incur the costs involved.
For both PMAs and LMAs, it is up to you to demonstrate that the benefits of the product outweigh any risks that may arise from them not providing all the data.
An authorised product will have a distribution category which relates to the retail supply of the product, eg. a product classified as Prescription Only Medicine - Veterinarian (POM-V) may only be supplied by a veterinary surgeon or a pharmacist and must be supplied in accordance with a prescription from a veterinary surgeon.
Further information about the distribution categories is in the guidance for retailers.
The distribution category of an Exceptional MA will be POM-V. It is possible to apply for a change in distribution category for PMAs from POM-V to POM-VPS once the product has been on the market for at least 12 months with a high volume of sales and the product:
- only makes preventative claims
- has a good record in terms of adverse events (AE) and Suspected Lack of Efficacy (SLE)
The distribution category of a MAPI product will be the same as the distribution category of the parent product.
The distribution category can also be referred to as the legal category.
Post authorisation steps
An MA must be renewed five years following initial authorisation.
Details about how to apply for a renewal can be found on the Apply to renew a marketing authorisation for a veterinary medicine page.
Note - Exceptional MAs are reassessed on an annual basis. A formal renewal may be required if this is specified as a condition on the initial authorisation
If you wish to make any changes to your MA you will need to submit a variation application to the VMD.
Details about how to apply for a variation can be found on the Apply to change a marketing authorisation for an animal medicine page.
Note - Exceptional MAs are subject to the same variation procedures as other types of MA.
UK Public Assessment Reports (UKPARs)
In most cases a public assessment report (PuAR) will be available on the Product Information Database (PID). The SPC, label text, and a post authorisation assessment (PAA) document will also be available. The PAA lists all applications conducted on a product since initial authorisation.
Only the SPC and PAA will be available for Exceptional MAs and Copycats.
For mutually recognised products where the UK acted as a CMS, the PuAR will be available from the member state that acted as the RMS for the procedure
For centrally authorised products, the SPC and PuAR will be available on the EMA website.
How to apply
Details about how to apply for a new Marketing Authorisation can be found on the Apply for a Marketing Authorisation for Veterinary Medicine page.