The pharmaceutical industry requires strict standards to ensure the quality and safety of medicines. As the main body for setting pharmaceutical standards in Europe, the EDQM (European Directorate for the Quality of Medicines & HealthCare) plays a key role in the qualification of analytical methods such as HPLC and GC. In this blog, we examine the EDQM processes and the impact of changes in the standardization of these methods.

The EDQM is part of the Council of Europe and has been working since 1964 to harmonise quality standards for medicines. It is responsible for publishing the European Pharmacopoeia, which contains over 3,000 binding standards for medicinal substances and test methods such as HPLC and GC.

European Pharmacopoeia Commission (EPC): Responsible for approving standards and updating them based on scientific advances.

CEP certificates: These certificates indicate that pharmaceutical substances comply with the standards of the European Pharmacopoeia, and to obtain them, manufacturers must comply with EDQM processes.

Classification of changes in standards

The EDQM divides changes in manufacturing and testing processes into three categories:
1. Notifications: changes that do not affect quality (e.g. administrative changes).
2. Minor Changes: changes that may affect quality (e.g. modification of test methods).
3. Major Changes: changes that are likely to have a major impact on quality (e.g. change in the synthesis route of materials).

EDQM standard method for monitoring changes in equipment qualification

1. Following the Q4 model for equipment qualification

EDQM uses the Q4 framework (Design, Installation, Operation, Performance) to ensure the quality of equipment. This model includes the following steps:

Design Qualification (DQ): Checking the conformity of the equipment design with the user requirements (URS) and functional requirements (FRS) before purchasing the device.

Installation Qualification (IQ): Verification of correct installation of equipment according to manufacturer’s instructions and EDQM standards, including checking connections, initial calibration, and documentation of installation details.

Operational Qualification (OQ): Testing the performance of the device within specified ranges (e.g. temperature, pressure, flow rate in HPLC/GC) and ensuring compliance with technical specifications.

Performance Qualification (PQ): Evaluating the performance of a device under actual production conditions and verifying its ability to produce repeatable and accurate results.

2. Change management based on EDQM classification

The EDQM divides changes in analytical methods or equipment into three categories:

Declarative changes: such as administrative reforms that do not require reassessment.

Minor changes: such as adjusting the column temperature in GC, which may affect the quality of results and require internal documentation and approval.

Major changes: such as replacing the HPLC detector or changing the separation method, which require submitting an application to the EDQM and obtaining a CEP certificate.

3. Use of high purity reference standards

EDQM Standards Reference: Reference materials used in HPLC and GC must comply with the European Pharmacopoeia (EP) and have a purity of at least 99.9% to reduce analytical errors.

Storage of standards: Prevent evaporation of solvents or chemical analysis by using controlled conditions (low temperature, limited range).

4. Updating documentation and coordinating with the European Pharmacopoeia

Regular review of EDQM publications: updating standards based on the latest version of the European Pharmacopoeia (e.g. version 11.0 in 2025) which includes changes in test methods or impurity limits.

Documenting changes: Record all amendments to the qualification protocols and submit a report to EDQM if required.

5. Conducting specialized validation tests

HPLC performance tests:

• Evaluate column resolution, retention time repeatability, and detector response linearity.

• Use of reference standards for accurate calibration.

GC performance tests:

• Check its temperature accuracy, carrier gas flow stability, and FID/MS detector sensitivity.

• Test to identify volatile impurities such as nitrosamines.

6. Cooperation with accredited laboratories and EDQM inspections

Periodic inspections: EDQM conducts inspections to verify the compliance of equipment with GMP standards. Preparation includes reviewing IQ/OQ/PQ documents and correcting possible deficiencies.

Use of partner laboratory services: for advanced calibration and validation of methods according to EP 11 standards.