Obtaining marketing authorisation for a medicinal product in the European Union is a rigorous and complex process, but it is not impossible. The European Medicines Agency (EMA) and national agencies manage this process. Pharmaceutical legislation is harmonised across the EU and it sets strict requirements to ensure the safety, efficacy, and quality of pharmaceuticals. These requirements are designed not only to protect public health, but also to maintain the high standards of pharmaceutical development and distribution within the EU.
In an industry where regulatory approval and fast access to the market are directly linked to a company’s ability to compete, understanding the requirements is essential. This blog aims to demystify the steps and requirements involved and clarify the different options to market entry available in the EU.
Marketing authorisation procedures in the EU
The European Union offers a range of regulatory pathways for the approval of medicinal products, each tailored to different types of medicines and specific market needs. This overview provides a detailed overview of each of these procedures:
1. Centralised Procedure
The Centralised Procedure (CP) is managed by the European Medicines Agency (EMA) and is mandatory for certain categories of medicines. These include:
- Biotechnology products, including recombinant DNA technology, controlled gene expression, and monoclonal antibody methods.
- Orphan drugs, which are medications intended for the diagnosis, prevention, or treatment of life-threatening or very serious diseases or disorders that are rare.
- Advanced therapy medicinal products, such as gene therapies, somatic cell therapies, and tissue-engineered products.
- Products containing a new active substance intended for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune diseases, and other immune dysfunctions, and viral diseases.
The CP is optional for other medicines containing new active substances for indications other than those stated above, for innovative therapeutic, scientific or technical products or whose authorisation would be in the interest of public or animal health at EU level.
The CP allows for the submission of a single marketing authorisation application to the EMA, which, if approved, gives positive opinion to EU commission to grant a marketing authorisation valid in all EU member states, as well as in the European Economic Area (EEA) countries (Norway, Iceland, and Liechtenstein). This is a particularly advantageous solution for companies seeking a broad market access, as it simplifies the regulatory process by eliminating the need to apply separately in each country.
2. Decentralised and Mutual Recognition Procedures
These procedures are applicable to products that do not fall under the mandatory scope of the centralised procedure.
- Decentralised Procedure (DCP): This is used when a product has not yet been authorised in any EU member state. A company selects one member state to assess the application (the Reference Member State, RMS). Other member states (Concerned Member States, CMS) are involved, and if there are no objections, the RMS’s assessment is mutually recognised by the CMSs, leading to national authorisations in several countries approximately at the same time.
- Mutual Recognition Procedure (MRP): Used when a product is already authorised in one EU member state (future Reference Member State, RMS). The holder of the authorisation may apply for this authorisation to be recognised in other EU member states (Concerned Member States, CMS). This is done by submitting the existing authority assessment along with an application to other member states, which agree to recognise the validity of the original, national marketing authorisation.
3. National Procedures
This pathway is used when a company seeks marketing authorisation in just one EU member state. This is often pursued for products that have a limited market or when a company is starting to expand its operations within Europe. The application is submitted to the national competent authority of the country where marketing is intended. Once approved, the marketing authorisation is only valid within that country.
Each of these procedures offers specific advantages and is designed to meet different strategic needs within the pharmaceutical industry. Choosing the right pathway is critical and depends on a product’s characteristics, intended markets, and commercial goals. This flexibility in regulatory pathways ensures that all types of medicinal products can find the most efficient and appropriate route to market access across the European Union.
Global pharma company & Medfiles: Cooperation in obtaining and maintaining marketing authorisations in the EU
“Medfiles has been a valuable partner for us during the registration and maintenance of products in Europe. They consistently provide prompt and accurate responses whenever there are inquiries or concerns related to European approvals.”
This is how a client from outside the EU, who has been working with Medfiles for 7 years, describes the partnership. The company initiated cooperation with Medfiles when they required assistance in entering the European market. The cooperation has involved applying for new marketing authorisations as well as managing products post-approval.
Key steps in the marketing authorisation process
Obtaining marketing authorisation in the EU is a complex process that requires careful planning and execution of each critical step. The path to marketing authorisation can vary in length depending on factors such as the type of product, the complexity of the application and the company’s responsiveness to regulatory feedback.
1. Pre-submission activities
Prior to submitting an application, companies are required to engage in pre-submission activities. This includes scientific advice meetings with the EMA or national authorities to discuss the regulatory strategy and any scientific concerns related to the product. These interactions can provide invaluable guidance on the adequacy of clinical trial designs, product safety profiling and data requirements, especially in the case of innovative products.
2. Submission of the marketing authorisation application
The marketing authorisation application is a comprehensive dossier that includes all data collected from the research and development phases. The information required for the dossier is described in the next chapter below.
3. Validation of the application
Upon receipt of the marketing authorisation application, the regulatory authority verifies that the dossier is complete and meets the necessary regulatory standards. This step is crucial as any missing or incomplete information can delay the review process.
4. Scientific evaluation
This phase involves a detailed assessment of the submitted data by the EMA’s Committee for Medicinal Products for Human Use (CHMP), Committee for Veterinary Medicinal Products (CVMP) or by national experts. This evaluation assesses the therapeutic benefits and risks associated with the product. The authorities usually request additional information or clarification from the applicant, which extends the evaluation timeline.
5. The decision
In the centralised procedure, the CHMP or the CVMP provides a scientific opinion on whether the medicinal product should be marketed. This opinion is then forwarded to the European Commission, which has the final authority to grant marketing authorisation for the product to be sold in the EU.
In other procedures, each national competent authority involved in the procedure will issue a marketing authorisation for the product, permitting it to be marketed in their country.
6. Post-authorisation surveillance and maintenance of the marketing authorisation
Even after a product has been authorised, pharmaceutical companies must continue to monitor its safety and efficacy. This involves the submission of periodic safety update reports, additional studies to confirm the benefit-risk balance, and pharmacovigilance activities to detect any adverse effects or other safety information not identified during the clinical trials.
It is the responsibility of the marketing authorisation holder to actively maintain the marketing authorisation. All changes that will affect the marketing authorisation documentation of the product must be reported to the competent authority using variation applications.
What to include to the marketing authorisation application?
The marketing authorisation application must be comprehensive and contain all the necessary documentation and data that regulatory authorities require to evaluate the safety, efficacy, and quality of the medicinal product. Each section of the marketing authorisation application is critical to the overall evaluation of the product by regulatory authorities. The data must be presented in a clear, organised manner following the applicable guidelines. The marketing authorisation dossier addresses the following key components:
Quality data (Module 3)
- Information about the active substance. There are different options on how the data can be included in the dossier (e.g. Active substance master file or CEP)
- Detailed information about the formulation, manufacturing process, and quality control of the medicinal product.
- Documentation covering the manufacturing site, raw material controls, product specifications, and stability data under various conditions.
Non-clinical data (Module 4)
- Data on pharmacology, toxicology, and pharmacokinetics, providing a preliminary assessment of the product’s safety before human testing.
- This stage is critical to understand the biological behaviour of the product and predict potential risks.
Clinical data (Module 5)
- The results from clinical trials that demonstrate the safety and efficacy of the product.
- These should comply with international Good Clinical Practice (GCP) standards and include diverse population groups to ensure broad applicability of the results.
Risk Management Plan (RMP)
- A comprehensive RMP is required to identify, characterise and minimise the risks associated with the medicinal product.
- This includes pharmacovigilance activities to monitor, assess and decrease the risk of adverse drug reactions (ADRs) or other related safety risks such as pregnancy, when using the medication.
Summary of Product Characteristics (SmPC), labelling, and Package Leaflet (PL)
- SmPC: Provides detailed information on the drug, including indications, dosages, contraindications, and potential side effects. It is the basis of information for healthcare professionals on how to use the medicinal product safely and effectively.
- Labelling and PL: Information that will appear on the drug’s packaging and the leaflet provided for patients, outlining how to use the medication safely and effectively.
Summary of Pharmacovigilance Safety Management Plan (PSMF)
- Qualified Person for Pharmacovigilance (QPPV), PSMF number and location registered to Article 57 database shall be available.
- PSMF should be provided to competent authorities within seven days of the request being made.
Please be aware that the submission of the application will result in specific pharmacovigilance responsibilities being triggered. Once the application has been submitted, the applicant is required to maintain a robust system to monitor and report adverse drug reactions, manage safety data through periodic updates, conduct risk assessments, and ensure ongoing communication with regulatory authorities.
In conclusion, obtaining marketing authorisation in the EU is a regulated and collaborative effort between pharmaceutical companies and regulatory authorities. Strict adherence to the outlined requirements and proactive engagement with the regulatory processes are key success factors. From selecting the appropriate marketing authorisation procedure to meticulously preparing the marketing authorisation application and maintaining robust pharmacovigilance practices, each step is critical.
Medfiles’ highly qualified team of experts has on average more than 10 years of experience in marketing authorisations and pharmacovigilance working both for the pharmaceutical industry and at the regulatory authorities. By partnering with us, you gain access to customised services tailored to your specific needs. We can take care of the entire marketing authorisation application process (DCP/MRP/CP/NP) for you, in any EU country, from registration strategy to marketing authorisation. You can also outsource only parts of your process to us.
Our dedicated and easily accessible team is available to support your project, and we provide transparent budget estimates with hourly billing. Additionally, we offer a secure platform for document sharing.
Read also:
- Entering the EU pharmaceutical market: Q&A on new marketing authorisations
- What does it take to enter the EU pharmaceutical market? Regulatory, supply chain and market access realities explained
- Marketing authorisation application processes efficiently under one roof – for all EU countries
- Centralised marketing authorisation process requires diverse expertise – Medfiles’ expertise employed as the driving force for a new veterinary MA
- How to write a strong Module 3 for a marketing authorisation application
- Q&A: What makes a strong Module 3 quality dossier
- Meet our people: New marketing authorisations for human medicines
