Navigating EU Marketing Authorisation: Key Routes and Procedures Explained

Centralised vs Decentralised vs Mutual Recognition Procedures

Marketing authorisation is a critical step for any medicinal product entering the European market. Unlike the US, where the Food and Drug Administration (FDA) handles approvals, Europe offers several complex regulatory pathways. This article explores the various marketing authorisation routes available in the European Economic Area (EEA), including the centralised procedure, decentralised procedure, mutual recognition procedure, and national authorisation. We’ll also look at special procedures for orphan drugs, paediatric medicines, and advanced therapies.

 

What is Marketing Authorisation?

A medicinal product can only be placed on the market in the European Economic Area (EEA) with a valid marketing authorisation. This authorisation can either be national, granted by a competent authority of a member state, or a Union-wide authorisation, granted for the entire European Union (EU). To qualify for a Union authorisation, the marketing authorisation holder must have an established office within the EEA, which includes EU member states, as well as Norway, Iceland, and Liechtenstein.

 

The Centralised Procedure

The centralised procedure is managed by the European Medicines Agency (EMA) and was introduced in 1995. It is compulsory for certain categories of products, including biotechnology-derived medicines, orphan drugs, and those treating serious conditions like cancer, HIV, and autoimmune diseases.

When to Use the Centralised Procedure

The centralised route is mandatory for:

  • Medicines derived from biotechnology.
  • Orphan medicinal products.
  • Products intended for serious conditions like HIV, cancer, and neurodegenerative diseases.

 

Application Process

The application is submitted directly to the EMA, which assesses the product via the Committee for Medicinal Products for Human Use (CHMP). After a 210-day evaluation process, the European Commission issues the final decision, valid across all member states. The total time can be longer if there are additional requests for information, inspections, or changes required during the process.

 

Mutual Recognition Procedure (MRP)

The Mutual Recognition Procedure is suitable for products already authorised in one EU member state. Once a product receives its initial authorisation in a member state, other member states can mutually recognise this authorisation.

Key Features of MRP:

  • The reference member state (RMS) where the product was first authorised prepares an assessment report.
  • Other concerned member states (CMS) review and approve the marketing authorisation based on this report.
  • Any disputes between states can be referred to a coordination group for resolution, and unresolved issues can be escalated to the EMA.

 

Decentralised Procedure (DCP)

Introduced in 2004, the Decentralised Procedure is similar to the MRP but is used when the product has not yet been authorised in any member state. It allows companies to apply for simultaneous marketing authorisation in multiple member states.

Key Features of DCP:

  • One member state is selected as the Reference Member State (RMS) to assess the application.
  • National marketing authorisations are granted based on the RMS’s evaluation.
  • The process takes about 210 days, similar to the MRP.

 

National Authorisation

National authorisation is used when a product is to be marketed in only one EU member state. This procedure is still available but is limited to situations where the company does not seek authorisation across multiple countries.

 

Orphan Drugs and Paediatric Medicines

Orphan Drugs
Orphan drug designation is granted for medicines intended for the treatment of rare diseases affecting fewer than five in 10,000 people in the EU. The EMA provides incentives, such as fee reductions and extended market exclusivity, to encourage the development of treatments for rare diseases.

Benefits of Orphan Drugs:

  • 10 years of market exclusivity.
  • Direct access to the centralised procedure.
  • Fee reductions for marketing authorisation applications and scientific advice.

 

Paediatric Medicines
The Paediatric Regulation, introduced in 2006, aims to improve the development of medicines for children. All new marketing authorisation applications must include a Paediatric Investigation Plan (PIP), detailing how the product will be researched for use in children.

Key Incentives:

  • 6-month extension of the Supplementary Protection Certificate (SPC) for completing the PIP.
  • Waivers and deferrals are available for medicines not suitable for paediatric use or those needing further adult data before paediatric studies.

 

Advanced Therapy Medicinal Products (ATMPs)

Advanced therapy products, including gene therapies, somatic cell therapies, and tissue-engineered products, fall under the ATMP category. These innovative products are regulated by a separate committee (Committee for Advanced Therapies, CAT) within the EMA.

Key Features of ATMPs:

  • Authorisation through the centralised procedure is mandatory.
  • Specific scientific guidelines for development.
  • Incentives for small and medium-sized enterprises (SMEs) to develop these therapies.

 

Special Application Types

Generic and Hybrid Applications
Generic applications (Article 10) are for products with the same qualitative and quantitative composition in active substances as the reference product, provided bioequivalence is demonstrated. Hybrid applications (Article 10b) are for medicines that differ slightly from the reference product, requiring additional data.

Well-Established Use (WEU) Applications
These are based on scientific literature demonstrating that the active substances have been in use for at least 10 years, with recognised efficacy and safety. However, this procedure is not frequently used due to the challenge of finding literature with sufficient detail.

 

Conclusion

Navigating the EU’s marketing authorisation procedures is complex due to the multiple routes available. Choosing the right procedure depends on the nature of the product, its intended market, and the therapeutic area. While the centralised procedure offers EU-wide authorisation, decentralised and mutual recognition procedures allow for flexibility in member state authorisations. Special considerations apply for orphan drugs, paediatric medicines, and advanced therapies, all of which have their own set of incentives and requirements.

Understanding these procedures and their intricacies is crucial for any company aiming to bring a medicinal product to the European market. For companies new to the EU regulatory framework, seeking scientific advice and early planning can significantly improve the chances of a smooth approval process.

 

FAQs
  1. What is the centralised procedure?
    • A marketing authorisation route managed by the EMA, offering EU-wide approval for specific categories of medicines.
  2. What is the difference between the decentralised and mutual recognition procedures?
    • The decentralised procedure is for products not yet authorised in any EU member state, while the mutual recognition procedure is used when a product has already been authorised in one member state.
  3. What are the benefits of orphan drug designation?
    • 10 years of market exclusivity, fee reductions, and direct access to the centralised procedure.
  4. What is the role of the Paediatric Investigation Plan (PIP)?
    • It ensures that medicines developed for adults are also investigated for paediatric use, granting a 6-month SPC extension if completed.
  5. What are Advanced Therapy Medicinal Products (ATMPs)?
    • ATMPs include gene therapies, cell therapies, and tissue-engineered products, which require centralised authorisation.

 

Written by Educo Life Sciences Expert, Adriaan Fruijtier

Adriaan Fruijtier graduated as a pharmacist at the University of Utrecht, The Netherlands. Since April 2004 he has been an independent regulatory affairs consultant. Until March 2004 he was Head of the Oncology Group within Global Regulatory Affairs at Bayer AG, Wuppertal, Germany, and Bayer Corporation, West Haven, CT, USA. Between 2001 and 2003 he was Director of Regulatory Affairs at Micromet AG, a biotech company in Munich, Germany. Prior to joining Micromet he has worked during four years as a Project Manager for Oncology Projects at the European Medicines Agency in London, United Kingdom. He joined the European Medicines Agency from Novartis AG, Basel, Switzerland, where he was Regulatory Affairs Project Manager in the Oncology group in 1996 and 1997. Before 1996 he was Head of Drug Regulatory Affairs for six years at Ciba-Geigy in the Netherlands and has worked as Manager of Regulatory Affairs at Glaxo, also in the Netherlands.

This article was written using materials from the course, Understanding EU Regulatory Affairs.

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