Newsletter Summer 2018 - Bart Van der Schueren on The European Regulatory Framework: Personal Perspective

Bart Van der Schueren, Ph. D, M.D., The European Regulatory Framework


Regulating drugs is challenging as it involves competing interests:  on the one hand regulatory bodies need to ensure that medicinal products are both safe and effective; on the other, there is intense pressure for innovative therapies to reach patients as soon as they are available.

European regulators rightly understood that harmonization was needed between its 28 (soon to be 27 because of Brexit) member states in terms of the requirements to obtain marketing authorization. 


European regulators rightly understood that harmonization was needed between its 28 (soon to be 27 because of Brexit) member states in terms of the requirements to obtain marketing authorization.  This “one stop” for regulatory approval within the European Economic Area (EEA; i.e., the 28 (soon to be 27) member states of  the European Union (EU), Iceland, Liechtenstein and Norway) has the obvious advantage of saving valuable time that was previously lost because of fragmented requirements and processes in each member state. In addition, it expands access to a much wider expertise available across all countries and a better monitoring of the safety of medicinal products throughout their life cycle.

It was this need for harmonization that led to the founding of the European Medicines Agency (EMA) in 1995 for the protection of public and animal health through the scientific evaluation and supervision of medicines.  The EMA’s Committee for Medicinal Products for Human Use (CHMP) is responsible for conducting the initial assessment of EU-wide marketing authorization applications, assessing modifications or extensions (‘variations’) to an existing marketing authorization, considering recommendations of the Agency's Pharmacovigilance Risk Assessment Committee  (PRAC) on the safety of medicines on the market, and when necessary, recommending European Commission changes to a medicine’s marketing authorization (including its suspension or withdrawal from the market). The centralized procedure is mandatory for human medicines for the treatment of HIV/AIDS, cancer, diabetes, neurodegenerative diseases, auto-immune and other immune dysfunctions and viral diseases. In addition, it is mandatory for all medicines derived from biotechnology processes, advanced therapy and orphan medicines. Potential marketing authorization holders (MAHs) of other medicinal products may opt for a centralized or decentralized procedure in one or more EU member states simultaneously.

Recognizing that his need for harmonization between member states created EMA is a key to better understanding how it differs from the Food and Drug Administration (FDA) in the U.S. The FDA developed as a consumer protection agency and has the advantage of centralization and common rules across the American States. The EU regulates medicinal products through a network of centralized and decentralized agencies throughout its member states and has to strike a difficult balance between harmonization while preserving national autonomy. This affects how marketing authorizations are assessed. Within the European system, two member states are nominated to assess a marketing authorization (rapporteur and co-rapporteur). They independently assess the marketing application in terms of quality, pre-clinical, pharmacokinetic and pharmacodynamic and clinical data until day 80.  Subsequently, their assessment and a list of outstanding issues are presented to all other member states for comments and a consolidated list of outstanding issues precluding marketing authorization is returned to the aspiring MAH.  Its responses are then assessed and discussed at CHMP, until a positive benefit risk balance can be established and CHMP can adopt a positive opinion for marketing authorization.  In addition, the post-approval measures and risk management plan are agreed upon between the PRAC and the aspiring MAH.

The total assessment time amounts to 210 days (or 150 days when accelerated), excluding ‘clock-stops,’ during which the aspiring MAH formulates responses and conducts additional analyses.  Ultimately, the applicant also has the opportunity to defend its position to all EU member states and Norway and Iceland during an oral explanation. The final decision is reached either by consensus or vote in which a majority is defined as 17 of the currently 28 members + 5 co-opted members (individual members of CHMP selected for their expertise). Norway and Iceland can comment, but do not have a vote within the system.

This process is different from what happens under the FDA, where medicines are approved by divisions with jurisdiction over therapeutic areas and modalities, and the agency is more broadly responsible for the safety and security of the food supply, all cosmetics, dietary supplements, health care products that use radiation and medical devices.  In contrast, EMA only regulates medicinal products.

The European attempt to harmonize drug approval has proven to be successful.  It remains however fundamentally different from the system in the US and also does not guarantee that a marketed drug with a demonstrated positive benefit risk will make it to patients.  This is the ultimate challenge in a continent where health care is provided and reimbursed by each individual member state.  There are attempts to improve the collaboration between payers and the regulatory agency.  However, it is easy to understand that this is a challenge in view of the heterogeneity of the financial capability of each member state.  Nonetheless, the European system has clearly demonstrated its value and will continue to do so for member states that opt in.  Brexit confronts EMA with the challenge of moving from London to Amsterdam and losing one of its most valuable members.  However, it is ultimately a spirit of cooperation that will ensure Europeans to have access to the best and most innovative medicinal products.  Honi soit qui mal y pense.


The views expressed by the author are his personal views and may not be understood or quoted as being made on behalf of or reflecting the position of European Medicines Agency (EMA) or one of its committees or working parties.