Understanding the Authorisations Required to Import and Distribute Pharmaceutical Products in the European Union

The importation and distribution of pharmaceutical products within the European Union (EU) are governed by rigorous regulations. These regulations, designed to ensure the protection of public health and safety, are intricate, reflecting the high-risk nature of pharmaceuticals. They necessitate vigilant oversight to prevent the distribution of falsified or counterfeit products. Today, I'd like to discuss the various types of authorisations needed for companies that want to import and distribute pharmaceuticals within the EU. This includes the Product authorisation itself (MA), the manufacturing and Import authorisation (MIA), and the Wholesale Distribution Authorisation needed to own and sell the medicine and, once on the market, the Pharmacovigilance system to assure the safety of the medicine. We will specifically look at the legal frameworks, specific licenses required, and the roles of key regulatory bodies.

The Legal Framework Governing Pharmaceutical Imports and Distribution in the EU

The rules for bringing in and distributing pharmaceutical products in the EU are mainly controlled by Directive 2001/83/EC (as amended). This directive outlines the EU's laws regarding medicines for human use, providing the essential legal framework for producing, distributing, and selling pharmaceuticals across the EU.  Regulation (EC) No 726/2004 sets out the procedures for authorising and supervising medicinal products at the EU level, with a particular focus on innovative medicines.

Other relevant legislation and guidelines include:

• Directive 2003/94/EC lays down principles and guidelines of good manufacturing practice (GMP) for medicinal products.
• Directive 2005/28/EC establishes principles and guidelines for good clinical practice (GCP).
• Regulation (EU) 2019/6 sets out the requirements for veterinary medicinal products.

Marketing Authorisations (MAs)

There are options to access unauthorised medicines via clinical trials or under the direct supervision of a physician; however, outside of these two specific routes, medicines must be authorised.  Before marketing, importing, or distributing within the EU, each pharmaceutical product must, therefore, secure a Marketing Authorisation (MA). The authorisation is an essential prerequisite, signifying that the product has undergone evaluation for safety, quality, and efficacy by either the European Medicines Agency or another National Competent Authority. There are several routes to obtaining an MA in the EU:

• Centralised Authorisation Procedure (CAP): Administered by the European Medicines Agency (EMA), the centralised procedure facilitates a single authorisation recognised across all EU member states. This mandatory process applies to specific categories of medications, including those designed for the treatment of HIV, cancer, diabetes, neurodegenerative diseases, and orphan drugs. The centralised procedure is also optional for other innovative products.
• Decentralised Procedure (DCP): This procedure is employed when a pharmaceutical product has not yet been authorised in any EU country. It enables a company to simultaneously apply for authorisation in multiple EU member states in parallel, with one member state assuming the lead role.
• Mutual Recognition Procedure (MRP): If a product has been authorised in one EU country, this procedure enables other member states to acknowledge and accept that authorisation.
• National Procedure: This procedure is used when a product is intended to be marketed in just one EU member state.

Obtaining a marketing authorisation involves submitting a detailed eCTD dossier that includes all of the information on the pharmaceutical form, manufacturing process, clinical trial data, risk-benefit analysis, and mock-ups of the proposed labelling and packaging.

Import Authorisation and GMP Certification

Importing pharmaceutical products into the EU requires a Manufacturers / Importers Authorisation (MIA). This authorisation is different from the Marketing Authorisation and is necessary for any organisation that wants to import medicines from outside the EU.

The Import Authorisation is issued by the Competent Authority in the member state into which the importation will occur. The key requirements for obtaining an Import Authorisation include:

• Compliance with Good Manufacturing Practice (GMP): The imported product must be manufactured in compliance with GMP, according to Eudralex Volume 4.  This is only verified following inspections by the National Competent Authority and upon issuing a GMP certificate.
• Qualified Person (QP) oversight: An EU Qualified Person must be in place, responsible for ensuring that each batch of imported product meets EU GMP standards and legislative requirements.
• Product testing: Imported products that originate from countries that do not have a mutual recognition agreement on the acceptance of testing must undergo separate testing within the EU to confirm that they meet the specifications approved in the MA.

Wholesale Distribution Authorisation (WDA) and Good Distribution Certification

Entities wishing to purchase or sell medicines within the EU are mandated to acquire a Wholesale Distribution Authorisation (WDA) for the wholesale distribution of pharmaceutical products, regardless of whether these products are imported or manufactured within the EU.

The WDA is issued by the Competent Authority in the country where the wholesaler is based. The application process entails demonstrating compliance with Good Distribution Practice (GDP) and other regulations, which should be outlined in the competent authorities' guidelines. Essential prerequisites for obtaining a Wholesale Distribution Authorisation (WDA) are as follows:

• Appropriate premises: The facilities used for storage and distribution must adhere to GDP standards, which include adequate space and security measures.
• Quality Management System: Implementing a quality management system to identify and mitigate risks in the distribution process.
• Proper transport and storage conditions: Ensuring that medicines are stored under conditions that prevent contamination, exposure to temperature extremes, degradation, or loss of efficacy.
• Appropriate and trained personnel: The Wholesaler must appoint a Responsible Person with the appropriate experience, education and training in GDP and the legal requirements of a WDA Holder.  Other staff must receive thorough training in GDP and pharmaceutical distribution requirements.

• Record-keeping: Wholesalers must keep thorough records of all transactions to ensure complete traceability of products.

Initial and regular inspections by the Competent Authority ensure that WDA holders are compliant and continue to comply with all the EU GDP chapters and any other pertinent regulatory requirements.  Once successfully inspected, the wholesaler is issued with a Good Distribution Practice or GDP certificate.

GDP certification is mandatory for wholesalers and other entities involved in distributing pharmaceuticals within the EU.

Pharmacovigilance System

In addition to tending to the physical and logistical requirements involved in importing and distributing pharmaceuticals, organisations must also establish and maintain a pharmacovigilance system. This system is designed to monitor the safety of pharmaceutical products after they have been placed on the market.

Key elements of a pharmacovigilance system include:

• Adverse event reporting: A system for collecting and reporting adverse events or side effects associated with using a pharmaceutical product.
• Risk management plans (RMPs): These are plans that outline how potential risks associated with a product will be managed and mitigated.
• Periodic safety update reports (PSURs): Regular reports that provide an update on the safety profile of a pharmaceutical product.

The oversight of the pharmacovigilance system requires the appointment or contracting of a Qualified Person Responsible for Pharmacovigilance (QPPV). The QPPV is responsible for ensuring the fulfilment of all regulatory requirements and the timely resolution of any safety concerns.

Other additional requirements for certain types of Medicines

Some medicines, like controlled substances, biological products, and radiopharmaceuticals, have extra regulations to follow. For instance:

• Controlled drugs (narcotics): Importers and distributors must obtain controlled drug licences under national drug control laws.
• Biological products: These products have specific authorisations and separate guidelines for their unique production processes.
• Radiopharmaceuticals: Due to their radioactive nature, these products require authorisations related to radiation safety and standard pharmaceutical regulations.

The importation and distribution of pharmaceutical products within the EU are managed by a comprehensive framework of regulations intended to guarantee the entry into the market of only those medicines that meet the highest levels of safety, quality and efficacy. From obtaining and complying with the Marketing Authorisation to navigating the intricacies of correct manufacturing and import according to GMP to complying with Good Distribution Practices and maintaining a robust pharmacovigilance system, entities bringing their medicines into Europe must navigate numerous regulatory requirements. For companies seeking to operate in this space, understanding and adhering to these regulatory requirements is essential for success.

Obtaining these various authorisations is a complex process, but with our highly experienced GXP experts, you can rest assured. We can help with all these authorisation types and conduct reviews of your existing processes. We can also assist with registering entities and finding appropriate premises assessments, develop phase-appropriate QMS, and assist with compiling and submitting your MA/MIA/WDA applications.

Our team can also provide RA, QP, QPPV, RP, and RPi services, whether on a consulting basis until your entity is established or via fixed-term contracts to augment your existing staff.

If you wish to use our services and are interested in the leanest path to getting pharmaceutical products into and onto the EU or UK market, please email us at admin@oriongxp.com or call the office at +353 (0)71 9810101 or in the UK at +44 (0)203 4750375.