Importation of Medicinal Products into the European Union

A focus on Batch Certification

The Importation of Medicinal Products into the European Union is complex and comes with several requirements ranging from licenses and authorizations to the Qualified Person, Batch Certification and Post Marketing activities.

Manufacturing and Importation License

The first step in the process is to obtain a Manufacturing and Importation License. This license is granted by the Competent Authority of the EU state where the importation occurs and is granted following a set of provisions including the availability of suitable and sufficient premises for the control and storage of these products, the availability of a Qualified Person (QP) who is at the constant disposal of the Importer and a Quality System that has been verified through inspection by the Competent Authority. The storage and testing facilities can be outsourced as long as these are audited by, or on behalf of the QP.

Marketing Authorization

The second step of the process to import Medicinal Products into the EU is to receive a Marketing Authorization (MA) from the Competent Authority. This is only available for applicants established in the EU and may be acquired by various channels; either applying for approval in several EU countries via the Centralized, De-Centralized or Mutual Recognition Procedures, or applying to a sole EU Competent Authority via a National Procedure. It is the Marketing Authorization Holder (MAH) that is ultimately responsible for the product in the EU Market.

Packaged and Labelled

The third step is to ensure that the product will be Packaged and Labelled according to EU Legislation and that the packaging will contain the safety features as required by the Falsified Medicines Directive (EU)2016/161.

Quality Control in the EU

Once a batch has been imported from a third country it is the QP’s (of the Importation License)   responsibility to ensure that the batch undergoes Quality Control in the EU unless there is a Mutual Recognition Agreement (MRA) between the EU and the third country. The countries that currently have a MRA in place with the EU are the following; Australia, Canada, Israel, Japan, New Zealand, Switzerland and the United States. The Quality Control includes analysis of all the parameters required by the product specification registered in the Marketing Authorization as well as a series of checks that the QP implements in order to ensure that the manufacturing has been performed according to the requirements of the Marketing Authorization (MA) and with Good Manufacturing Practice (GMP).

Batch Certification by the QP

The process of batch certification by a QP includes, but is not limited to, the following:

• A check that the bulk manufacturing site and packaging site (if different) holds a current EU GMP Certificate and is listed on the MA;
• A check that the batch packaging site holds a current EU GMP Certificate and is listed on the MA;
• A review of the batch manufacturing and packaging records to ensure that:
  • All In Process Control Tests (IPC) have been performed at the required intervals and meet limits 
  • All manufacturing steps are as per the MA 
  • Any deviations encountered are investigated and acceptable 
  • Batch records have been approved by all required personnel 
  • Correct Raw Materials and Packaging Materials have been used
• MA number and MAH are listed correctly on the packaging; 
• Batch Serialization/Bollini- application has been performed; 
• A check that samples have been collected by a QP or delegate; 
• Ensuring that the site of Analysis in the EU is listed on the MA and holds a current GMP Certificate; 
• Ensuring that test methods used comply with the MA; 
• Ensuring that all results meet specifications on the MA and all testing has been fulfilled;
• A check that any Out of Specification or Out of Trend results have been suitably investigated; 
• Ensuring that ongoing stability data supports the shelf life of the batch;
• Ensuring that any open complaint investigations or recalls do not have any possible impact on the current batch;
• Ensuring that any post-marketing commitments are being or have been fulfilled;
• Ensuring that all audit reports for third party activities, such as manufacturing and testing, are reviewed and are still valid;
• Ensuring that all Quality Technical Agreements with third parties are valid.  

Once the QP is satisfied that the batch is of the required Quality, Safety and Efficacy the batch can be certified. The certification of a medicinal product by the QP is first recorded in a register that must be maintained and available to the Competent Authority for a minimum of five years. Following this, a Batch Release Certificate (BRC) is prepared.  The BRC contains details of the Importer, batch, destination country and the statement in which the QP certifies that all the manufacturing stages of the batch of finished product have been carried out in full compliance with the GMP requirements of the EU and with the requirements of the Marketing Authorization(s) of the destination country/countries as well as the date, name and signature of the QP performing the release.

The Last Step Pharmacovigilance (PV)

The last step of the process is to ensure that a Pharmacovigilance (PV) process has been put in place. PV systems are established by the different Member States in order to continuously monitor the safe use of medicinal products which have been placed on the market, collecting and evaluating information on misuse and abuse of these products, adverse reactions and side effects. It is expected that the holder of each MA implements a similar system where the MAH has a Qualified Person responsible for PV (QPPV) at his disposal at all times. The MAH and QPPV need to maintain and make available on request a pharmacovigilance system master file, implement a risk management system for each medicinal product, monitor the results of risk reduction measures, take measures to ensure the safe use of the medicinal product, comply with obligations on the recording or reporting of suspected adverse reactions, conduct post-authorization safety studies and submit periodic safety update reports.

by Rachel (Gatt Rutter) Percival, GMP/ GDP Compliance Principal Consultant & Qualified Person @PQE Group