European Medicines Agency
The European Medicines Agency (EMA) is responsible for the scientific evaluation of centralized marketing authorization applications (MAA’s). A marketing authorization (MA) is the authorization of a medicine to be sold in one, several, or all the European Union’s member states, depending on the type of application that has been submitted and to which agency. A key difference between the EMA and other regulatory bodies such as the US Food and Drug Administration (FDA) is that it has no authority to authorize medicinal products, rather it makes a recommendation for the approval of an application to the European Commission who have the final legally binding decision.
When it comes to obtaining a marketing authorization, there are two options: Centralized procedure and National Authorization procedures.
The centralized marketing authorization, once approved by the European Commission, is valid in all 27 EU member states, as well as in the European Economic Area (EEA) countries Iceland, Norway, and Liechtenstein.
The Agency issues an opinion through the centralized procedure, which culminates in a single marketing authorization for the entire European Union. It also means that healthcare professionals and patients will have access to a single set of product information in all the European Union’s official languages. The following classification of products are compulsory to go through the centralized procedure:
- Medicines for rare diseases (orphan drugs)
- Neurodegenerative diseases
- Auto-immune conditions
- Viral diseases
- Advanced Therapy Medicinal Products (ATMP’s) such as cell and gene therapies
Some product types, such as those produced from biotechnology and genetic engineering, must also be submitted to the Agency. The EMA maintains committees and working groups dedicated to evaluating these products and disease categories.
An application for a new medicine can take up to 210 ‘active’ days to be evaluated. At least one clock stop occurs during this active review period, during which the applicant prepares responses to questions from the EMA’s Committee for Medicinal Products for Human Use (CHMP). The clock stops after day 120, and potentially after day 180 when the CHMP has created a list of questions or lingering issues that the applicant must resolve. Each month, the CHMP holds a meeting whereby it reviews current applications. By day 210, the application assessment is reported and the CHMP issues an opinion, positive or negative, in relation to the medicine in question. Given that the EMA does not have the legal authority to authorize a medicine, it presents its opinion to the European Commission who makes a legally binding decision within 67 days. These timelines can be accelerated with prior permission in specific cases, with an accelerated approval process usually issuing an opinion within 150 days once CHMP has determined that the medicine in question offers significant benefit to public health and therapeutic innovation.
Additional Types of Approvals
Conditional Approval can be granted on a risk/benefit approach as unmet needs will be met, and the benefits of immediate use and availability outweigh the risks associated with the lack of comprehensive clinical data provided. These approvals are valid for one year and can be renewed.
Exceptional Circumstances approval is given to medicines when the applicant is unable to produce data on the medicine’s efficacy and safety. This is seen frequently when dealing with rare and ultra-rare indications/diseases as populations for these conditions are so unique that it may be unreasonable or unethical to collect comprehensive information.
National Authorization Procedures
1. Decentralized Procedure
The decentralized procedure is the process of simultaneously authorizing medications in multiple European Union member states, utilized for medicines that do not have to go through the centralized system and have not been approved in any other EU member state previously. An identical marketing authorization application is submitted to the competent authorities of the Reference Member State and the Concerned Member States at the same time. The draft assessment report, SPC, labelling, and package leaflet, as presented by the Reference Member State, are approved by the Concerned Member States.
A coordination group (CMDh) is referred to in the instance that a member state refuses to approve an assessment. If no agreement is obtained within the 60-day limit, the procedure is submitted for arbitration to the appropriate EMA scientific committee (e.g. CHMP) for evaluation.
2. Mutual Recognition
Mutual Recognition is a procedure through which the authorization of a medicine in one European Union Member State is recognized by another Member State. A key point to this procedure, and difference to the above decentralized procedure, is that a medicinal product must have already been granted marketing authorization in one EU nation.
A mutual recognition request can be addressed to one or more EU nations and all EU nations must be notified, with applications required to be identical. The country responsible for reviewing the application, the Reference Member State, informs the other Concerned Member States. This review process can take up to 210 days before a recommendation for the application’s approval is provided by the Reference Member State. Following this, the Concerned Member States have 90 days to accept the Reference Member State’s decision as well as the summary of product attributes, labelling, and packaging. Within 30 days, national marketing authorizations are approved.
Should a member state refuse to recognise the original national authorization, the same process as outlined in the Decentralized Procedure is followed whereby the CMDh is referred to.
3. National Authorization Procedure
Member states in the EU have their own individual national authorization procedures, with their own competent authorities. Any medicine that goes through the national authorization procedure is evaluated at national level by the competent authority in that EU member state. Should a company wish to make their product available, and it does not fall into the remit of the centralized procedure, they can then apply for a marketing authorization with the relevant competent authority. These country-specific procedures differ from the decentralized route whereby multiple countries can be submitted to in parallel for authorization.
The information presented within this blog is for illustration purposes only and is not to be considered as professional advice. Any information related to health contained within this article is not a substitute for appropriate medical advice from licensed healthcare professionals.