Medicines Approval system

Whether for human or veterinary use a medicinal product must be the subject of a valid Marketing Authorisation (MA) before it can be placed on the market for sale and supply. The Marketing Authorisation Holder (MAH) has to market the product in compliance with the terms of the authorisation.

MAs issued only allow the product in question to be marketed by the MAH in that EU Member State, unless the product has been authorised via the centralised procedure in which case a single MA (a Community Authorisation) is granted by the European Commission and is considered valid in all EU Member States.

All applications for a MA are assessed based on supporting data provided for safety, quality and efficacy. A product only receives a MA if its benefits outweigh any risks.

Not all products for which MA applications are submitted are subsequently granted a Marketing Authorisation. Some applications are refused due to insufficient and/or inadequate data.

A national Marketing Authorisation (MA) is initially valid for five years from the date of first authorisation. At the end of the five year period it will be subject to renewal, which is a mechanism for reviewing the product to ensure the benefit/risk balance remains favourable. This review takes into consideration any further information obtained about the product from the experience gained of its use since it was first authorised, e.g. pharmacovigilance data. This is to ensure that the product's MA is still appropriate. Following this review the MA will be valid indefinately, or the MAH will be asked to submit another renewal in a further five year's time. 

EU Legislation - The body of EU legislation in the pharmaceutical sector is compiled in Volume 1 and 5 of the publication "Rules governing medicinal products in the EU" http://ec.europa.eu/health/documents/eudralex/index_en.htm

EU Directives are implemented through national legislation.

There are four different routes to obtaining a Marketing Authorisation (MA) which result in the issue of three different types of MA; a National only MA, a Mutually Recognised MA or a Community Authorisation. These routes determine the procedures, processes and timelines used in progressing an application for a new MA in accordance with EU legislation. Once granted, the authorisation will be classified as nationally authorised, mutually recognised or centrally authorised.

• A nationally authorised product is one that has been assessed and approved on a national basis only, i.e. there has been no interaction with other Member States. For information about nationally authorised products please visit the website of your national health authority.
• A mutually recognised product is one that has been assessed and approved at a European level involving at least two Member States, i.e. evaluated via the mutual recognition or decentralised procedure.
  For information about mutually recognised products please visit the MRI Product Index (Human) or the VMRI Product Index (Vet)
• A centrally authorised product is one that has been assessed and approved on a community level involving all EU Member States.
  For information about centrally authorised products please visit the EMA website

The centralised procedure is a European authorisation route resulting in a centrally authorised product with a single Marketing Authorisation.

If a product has been authorised using the centralised procedure it has been assessed on an EU wide basis and approved by the European Commission. The European Medicines Agency (EMA) organises the process of evaluation using scientific expertise from the Member States.

The centralised procedure is compulsory for some products and optional for others. Some products are not eligible for the centralised procedure.

More information about the EMA and the centralised procedure is available on their website: www.ema.europa.eu

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 Member State on a national basis and the Marketing Authorisation Holder wishes to obtain a Marketing Authorisation (MA) for the same product in at least one other Member State.

The Member State that has already authorised the product is known as the Reference Member State (RMS). The RMS submits their evaluation of the product to other Member State/s, these are known as Concerned Member States (CMS). The CMS is asked to mutually recognise the MA of the RMS.

If the applicant is successful, the CMS will then issue a MA for that product permitting the marketing of that product in their country.

The decentralised procedure (DCP) is a European authorisation route resulting in a mutually recognised product (MRP).

The difference between MRP and DCP is that a product must already be authorised in at least one Member State on a national basis in order for MRP to be used. DCP may be used if the product is not already authorised in any Member State, but does not want to use the centralised procedure, or the product is not eligible for the centralised procedure.

One of the proposed Member States will be asked by the applicant company to act as Reference Member State (RMS). The RMS does the initial evaluation of the product and issues a draft assessment report. The other Member States, known as the Concerned Member States (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 Member State will then issue a MA for that product permitting it to be marketed in their country.

A referral is a procedure used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. The medicine, or the class of medicines, is ‘referred’ to the European Medicines Agency, so that it can make a recommendation for a harmonised position across the European Union (EU).
Referrals can be started by the European Commission, any Member State or by the company that markets the medicine.
For most referrals, the European Commission issues a decision to all Member States reflecting the measures they need to take to implement the Agency’s recommendation.

For more information about referral procedures and the committees assessing the referrals related to different issues please visit the EMA website.
For information about European Commission decisions on referrals please refer to the EMA website.