Quality & use of medicines

Reference standards

The EDQM ensures the supply of official European Pharmacopoeia reference standards to help safeguard the quality and availability of medicines in Europe and beyond. Official reference standards are essential for the application of the quality control tests described in Ph. Eur. texts. Quality and medicines control laboratories, among others, require these official standards to perform the analytical procedures described in the monographs.

Activities

The extensive Ph. Eur. reference standard portfolio consists of 3 220 reference standards that are used to ensure the quality of medicines. In 2024, the EPC adopted 236 reference standards based on establishment reports prepared by the EDQM Laboratory. The EDQM distributes its reference standards worldwide, with its portfolio continually evolving to meet the requirements of new or revised Ph. Eur. texts, and existing ones are replaced as necessary when stocks are depleted. Managing this portfolio requires a comprehensive approach, involving tasks that range from procuring candidate materials to characterising and establishing standards, followed by manufacturing, quality control, quality assurance and release. Distribution and ongoing monitoring of these standards are essential to ensuring their relevance and reliability. In 2024, Ph. Eur. reference standards were distributed directly to 127 countries, illustrating the global importance of the EDQM’s work and its impact on public health.

Joint programmes

Activities in the Biological Standardisation Programme (co-funded by the European Union) led to the adoption of one new reference standard (Golimumab BRP batch 1) and two replacement batches (Human anti-D immunoglobulin BRP batch 2, and Heparin LMM for calibration CRS batch 6) linked to studies BSP164, BSP176 and BSP121, respectively.

International co-operation

Collaboration with WHO

The EDQM is responsible for establishing, manufacturing, monitoring and distributing WHO International Chemical Reference Substances (ICRSs). Currently, the ICRS catalogue consists of 211 reference standards. ICRSs are used worldwide in conjunction with the texts of the International Pharmacopoeia, which is published and maintained by WHO.

In 2024, the WHO Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) adopted eight new ICRSs and four replacement ICRS batches based on establishment reports submitted by the EDQM Laboratory. In addition, it issued two reports on the verification of the suitability of reference standard candidates (and/or corresponding establishment strategies), three reports on feasibility studies of production by advanced manufacturing techniques, three reports on the extension of the use of existing ICRSs and finally one report on the determination of a specific absorptivity value in the context of the revision of a monograph.

The EDQM is also responsible for manufacturing, establishing, storing and distributing WHO International Standards for Antibiotics (ISAs), which are essential for the standardisation and quality control of antibiotic active substances and medicinal products. There are currently 23 reference standards in the ISA catalogue.

Collaboration with ISO

The EDQM continued its participation as liaison organisation in the activities of ISO TC 334, the ISO Technical Committee on Reference Materials

Collaboration with national laboratories

The EDQM Laboratory can count on a number of official laboratories for support when collaborative studies are required for the establishment of Ph. Eur. reference standards. In 2024, 28 OMCLs, representing 19 countries, enrolled in such establishment studies.

Publications, databases and website

Throughout 2024, the EDQM continued to run and maintain its Reference Standards Online Database (https://crs.edqm.eu), providing access to all standards officially valid for the uses prescribed in Ph. Eur. monographs. Reference standards can be searched by code, name, monograph number or CAS number. In addition, batch validity statements are available to users to document the validity of the particular reference standard batch supplied at the time of use. Downloadable Safety Data Sheets and Biological Safety Data Statements, as well as leaflets, are also available in the EDQM’s online database.

Guideline/document de recommandation	Statut	*Commentaire*
Annexe IV de « Qualification of Equipment » – « Qualification of IR Spectrophotometers »	achevé	passé en revue
« Management of Reagents »	achevé	passé en revue
Annexe VI de « Qualification of Equipment » – « Qualification of Piston Operated Volumetric Apparatus (POVA) »	en cours	révision
Annexe XI de « Qualification of Equipment » – « Qualification of Analytical Columns »	en cours	révision
Annexe VII de « Qualification of Equipment » – « Qualification of Mass Spectrometers »	en cours	révision
Annexe 3.4 de « Evaluation and Reporting of Results » – « Verification of Out-Of-Specification Results in Animal Testing »	en cours	révision
Annexe 4 de « Evaluation of Measurement Uncertainty » – « Estimation of the Measurement uncertainty for the Biological Methods »	en cours	nouveau texte

Guideline/Recommendation documents	Status	Comment
Annex IV to Qualification of Equipment – Qualification of IR Spectrophotometers	Finalised	Reviewed
Management of Reagents	Finalised	Reviewed
Annex VI to Qualification of Equipment – Qualification of Piston Operated Volumetric Apparatus (POVA)	In progress	Revision
Annex XI to Qualification of Equipment – Qualification of Analytical Columns	In progress	Revision
Annex VII to Qualification of Equipment – Qualification of Mass Spectrometers	In progress	Revision
Evaluation and Reporting of Results – Appendix 3.4 “Verification of Out-Of-Specification Results in Animal Testing”	In progress	Revision
Annex 4 to “Evaluation of Measurement Uncertainty” – “Estimation of the Measurement uncertainty for the Biological Methods”	In progress	New draft

European Directorate for the Quality of Medicines & HealthCare