As an American Pharmaceutical Quality professional who has worked in and with European colleagues for decades, I am used to hearing, “But the requirements in country X are different,” to which my response is always, “Prove it.”

EudraLex represents the cornerstone of Good Manufacturing Practice (GMP) regulations within the European Union, providing a comprehensive framework that ensures medicinal products meet stringent quality, safety, and efficacy standards. You will understand the fundamentals if you know and understand Eudralex volume 4. However, despite this unified approach, a few specific national differences exist in how a select few of these regulations are interpreted and implemented – mostly around Qualified Persons, GMP certifications, registrations and inspection types.

EudraLex: The European Union Pharmaceutical Regulatory Framework

EudraLex serves as the cornerstone of pharmaceutical regulation in the European Union, providing a structured approach to ensuring medicinal product quality, safety, and efficacy. The framework is divided into several volumes, with Volume 4 specifically addressing Good Manufacturing Practice (GMP) for both human and veterinary medicinal products. The legal foundation for these guidelines stems from Directive 2001/83/EC, which establishes the Community code for medicinal products for human use, and Directive 2001/82/EC for veterinary medicinal products.

Within this framework, manufacturing authorization is mandatory for all pharmaceutical manufacturers in the EU, whether their products are sold within or outside the Union. Two key directives establish the principles and guidelines for GMP: Directive 2003/94/EC for human medicinal products and Directive 91/412/EEC for veterinary products. These directives are interpreted and implemented through the detailed guidelines in the Guide to Good Manufacturing Practice.

Structure and Implementation of EU Pharmaceutical Regulation

The EU pharmaceutical regulatory framework operates on multiple levels. At the highest level, EU institutions establish the legal framework through regulations and directives. EU Law includes both Regulations, which have binding legal force in every Member State, and Directives, which lay down outcomes that must be achieved while allowing each Member State some flexibility in transposing them into national laws.

The European Medicines Agency (EMA) coordinates and harmonizes at the EU level, while national regulatory authorities inspect, license, and enforce compliance locally. This multilayered approach ensures consistent quality standards while accommodating certain national considerations.

For marketing authorization, medicinal products may follow several pathways:

Authorizing body	Procedure	Scientific Assessment	Territorial scope
European Commission	Centralized	European Medicines Agency (EMA)	EU
National authorities	Mutual Recognition, Decentralized, National	National competent authorities (with possible additional assessment by EMA in case of disagreement)	EU countries concerned

This structure reflects the balance between EU-wide harmonization and national regulatory oversight in pharmaceutical manufacturing and authorization.

National Variations in Pharmaceutical Manufacturing Requirements

Austria

Austria maintains one of the more stringent interpretations of EU directives regarding Qualified Person requirements. While the EU directive 2001/83/EC establishes general qualifications for QPs, individual member states have some flexibility in implementing these requirements, and Austria has taken a particularly literal approach.

Austria also maintains a national “QP” or “eligible QP” registry, which is not a universal practice across all EU member states. This registry provides an additional layer of regulatory oversight and transparency regarding individuals qualified to certify pharmaceutical batches for release.

Denmark

Denmark has really flexible GMP certification recognition, but beyond that no real differences from Eudralex volume 4.

France

The Exploitant Status

The most distinctive feature of the French pharmaceutical regulatory framework is the “Exploitant” status, which has no equivalent in EU regulations. This status represents a significant departure from the standard European model and creates additional requirements for companies wishing to market medicinal products in France.

Under the French Public Health Code, the Exploitant is defined as “the company or organization providing the exploitation of medicinal products”. Exploitation encompasses a broad range of activities including “wholesaling or free distribution, advertising, information, pharmacovigilance, batch tracking and, where necessary, batch recall as well as any corresponding storage operations”. This status is uniquely French, as the European legal framework only recognizes three distinct positions: the Marketing Authorization Holder (MAH), the manufacturer, and the distributor.

The Exploitant status is mandatory for all companies that intend to market medicinal products in France. This requirement applies regardless of whether the product has received a standard marketing authorization or an early access authorization (previously known as Temporary Use Authorization or ATU).

To obtain and maintain Exploitant status, a company must fulfill several requirements that go beyond standard EU regulations:

1. The company must obtain a pharmaceutical establishment license authorized by the French National Agency for the Safety of Medicines and Health Products (ANSM).
2. It must employ a qualified person called a Chief Pharmaceutical Officer (Pharmacien Responsable).
3. It must designate a local qualified person for Pharmacovigilance.

The Pharmacien Responsable: A Unique French Pharmaceutical Role

Another distinctive feature of the French health code is the requirement for a Pharmacien Responsable (Chief Pharmaceutical Officer or CPO), a role with broader responsibilities than the “Qualified Person” defined at the European level.

According to Article L.5124-2 of the French Public Health Code, “any company operating a pharmaceutical establishment engaged in activities such as purchasing, manufacturing, marketing, importing or exporting, and wholesale distribution of pharmaceutical products must be owned by a pharmacist or managed by a company which management or general direction includes a Pharmacien Responsable”. This appointment is mandatory and serves as a prerequisite for any administrative authorization request to operate a pharmaceutical establishment in France.

The Pharmacien Responsable holds significant responsibilities and personal liability, serving as “a guarantor of the quality of the medication and the safety of the patients”. The role is deeply rooted in French pharmaceutical tradition, deriving “directly from the pharmaceutical monopoly” and applying to all pharmaceutical companies in France regardless of their activities.

The Pharmacien Responsable “primarily organizes and oversees all pharmaceutical operations (manufacturing, advertising, information dissemination, batch monitoring and recalls) and ensures that transportation conditions guarantee the proper preservation, integrity, and safety of products”. They have authority over delegated pharmacists, approve their appointments, and must be consulted regarding their departure.

The corporate mandate of the Pharmacien Responsable varies depending on the legal structure of the company, but their placement within the organizational hierarchy must clearly demonstrate their authority and responsibility. This requirement for clear placement in the company’s organization chart, with explicit mention of hierarchical links and delegations, has no direct equivalent in standard EU pharmaceutical regulations.

Germany

While Germany has many distinctive elements—including the PZN identification system, the securPharm verification approach, specialized distribution regulations, and nuanced clinical trial oversight—the GMPs from Eudralex Volume 4 are the same.

Italy

Italy has implemented a highly structured inspection system with clearly defined categories that create a distinctive national approach to GMP oversight. 

• National Preventive Inspections
  • Activating new manufacturing plants for active substances
  • Activating new manufacturing departments or lines
  • Reactivating departments that have been suspended
  • Authorizing manufacturing or import of new active substances (particularly sterile or biological products)
• National Follow-up Inspections to verify the GMP compliance of the corrective actions declared as implemented by the manufacturing plant in the follow-up phase of a previous inspection. This structured approach to verification creates a continuous improvement cycle within the Italian regulatory system.
• Extraordinary or Control Inspections: These are conducted outside normal inspection programs when necessary for public health protection.

Spain

The differences in Spain are mostly on the way an organization is registered and has no impacts on GMP operations.

Regulatory Recognition and Mutual Agreements

EU member states have received specific recognition for their GMP inspection capabilities from international partners individually.