Quality & use of medicines

Reference standards

The EDQM ensures the supply of Ph. Eur. reference standards (RSs) to help safeguard the availability of quality medicines in Europe and beyond. Official RSs are an integral part of the Ph. Eur. since they are used in conjunction with Ph. Eur. documentary standards to perform the analytical procedures described in monographs.

Activities

The Ph. Eur. reference standard portfolio consists of 3 171 RSs. In 2023, the European Pharmacopoeia Commission (EPC) adopted 235 RSs based on establishment reports submitted by the EDQM Laboratory.

The EDQM distributes its RSs worldwide and its portfolio is constantly evolving: new standards are regularly introduced to be used with new or revised Ph. Eur. texts, or to replace existing RSs when corresponding stocks run out. The overall life cycle management of the RS portfolio involves a wide variety of tasks, ranging from the procurement of candidate materials, characterisation and establishment, to manufacturing, quality control, quality assurance, release, distribution and monitoring.

The EDQM distributed Ph. Eur. RSs directly to 135 countries in 2023 (131 in 2022).

Joint programmes

The international collaborative studies (co-funded by the European Union) performed in 2023 as part of the Biological Standardisation Programme (BSP) led to the adoption of four reference standard replacement batches:

Establishment of Immunoglobulin BRP replacement batches (BSP150)
Establishment of Erythropoietin for physicochemical tests CRS replacement batch (BSP159)
Establishment of Hepatitis A virus coating reagent for ELISA BRR replacement batch (BSP165)
Establishment of Prekallikrein activator in albumin BRP replacement batch (BSP167).

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 212 RSs. ICRSs are used worldwide in conjunction with the texts of the International Pharmacopoeia, which is published and maintained by the WHO Expert Committee on Specifications for Pharmaceutical Preparations.

In 2023, the WHO ECSPP adopted two new ICRSs based on establishment reports submitted by the EDQM Laboratory. In addition, nine reports were issued on the verification of the suitability of RS candidates (and/or corresponding establishment strategies) and another two on feasibility studies of production by advanced manufacturing techniques.

The EDQM is also responsible for establishing, manufacturing, storing and distributing WHO International Standards for Antibiotics (ISAs), which are essential for the standardisation and quality control of antibiotic drug substances and medicinal products. There are currently 24 RSs 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 2023, 27 official medicines control laboratories, representing 22 countries, enrolled in such RS establishment studies.

Publications, databases and website

Throughout 2023, the EDQM continued to run and maintain its Reference Standards Online Database (https://crs.edqm.eu), providing access to all reference standards officially valid for the uses prescribed in Ph. Eur. monographs. RSs can be searched by code, name, monograph number or CAS number. In addition, RS batch validity statements are available to users to document the validity of the particular RS 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	GUIDELINE
Préface et avis aux lecteurs et lectrices des documents MQ	Adopté	Notes explicatives
« Interpretation of Screening Results for Unknown Peptides and Proteins by Mass Spectrometry based Methods »	Adopté	Document de recommandation
« Qualification of Equipment » – document de base	Adopté	Guideline
Annexe I de « Qualification of Equipment » – « Qualification of LC Equipment »	Adopté	Guideline
Annexe VII de « Qualification of Equipment » – « Qualification of Mass Spectrometers »	Adopté	Guideline
Annexe VIII de « Qualification of Equipment » – « Qualification of Balances »	Adopté	Guideline
« Management of OMCL Network Documents and Records by the EDQM »	Publié	Procédure
Annexe VI de « Qualification of Equipment » – « Qualification of Piston Pipettes »	En cours de révision	Guideline
Annexe 3.4 de « Evaluation and Reporting of Results » – « Special Considerations for Animal Testing in Connection with Verification of Out-Of-Specification Results »	En cours de révision	Guideline

Guideline/Recommendation document	Status	Guideline
Preface and Notes for Use of QM Documents	Adopted	Explanatory notes
Interpretation of Screening Results for Peptides and Proteins by Mass Spectrometry-based Methods	Adopted	Recommendation document
Qualification of Equipment – Core Document	Adopted	Guideline
Annex I to Qualification of Equipment – Qualification of PC Equipment	Adopted	Guideline
Annex VII to Qualification of Equipment – Qualification of Mass Spectrometers	Adopted	Guideline
Annex VIII to Qualification of Equipment – Qualification of Balances	Adopted	Guideline
Management of OMCL Network Documents and Records by the EDQM	Published	Procedure
Annex VI to Qualification of Equipment – Qualification of Piston Pipettes	Under revision	Guideline
Annex 3.4 to Evaluation and Reporting of Results: Special Considerations for Animal Testing in Connection with Verification of Out-Of-Specification Results	Under revision	Guideline