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.
Product types
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
Authorisation routes
There are four routes that can be used to get an MA:
- National
- Centralised
- Mutual Recognition
- Decentralised
These routes determine the procedures, processes and timelines used in processing an application for a new MA. Once granted, the authorisation will be centrally authorised, or nationally authorised even if submitted under the mutual recognition or decentralised routes.
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 CVMP 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 the EMA 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 sale and supply 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 route 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 simultaneously, 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.
Legal bases
There are seven 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(1) – generics
- Article 13(3) – generic hybrids
- Article 13(4) – biosimiliars
- Article 13(a) – bibliographic (well-established use)
- Article 13(b) – fixed combination
- Article 13(c) – Informed consent
You may also apply to extend an existing MA, under Regulation 1234/2008 as amended by 712/2012 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.
Generics
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, or part of the Global Marketing Authorisation where 10 years has lapsed from original authorisation, 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 / or working 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.
Generic-Hybrids
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, withdrawal period 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.