Supplement 11.3 of the European Pharmacopoeia (Ph. Eur.) is now available. Holders of Certificates of suitability to the monographs of the Ph. Eur. (CEPs) are invited to update their applications according to the revised monographs that will be implemented on 1 January 2024, and to follow the instructions given below.

The table at the end of this announcement provides a list of substances covered by a CEP and for which a revised monograph will be implemented on 1 January 2024 in Supplement 11.3 of the Ph. Eur.

According to Directives 2001/83/EC and 2001/82/EC, as amended, it is the responsibility of the manufacturer to comply with the current version of a Ph. Eur. monograph, and therefore to update the specification when a revised monograph is issued. In addition, the European Directorate for the Quality of Medicines and HealthCare (EDQM) ensures that CEPs refer to the most recent version of a Ph. Eur. monograph at any time.

The need to submit information to the EDQM following a revised monograph depends on the changes made to the monograph. Updates to the monographs are classified by the EDQM into two categories, labelled “Case A” and “Case B”, and this influences the information required. In the list of revised monographs below, it is indicated which classification (“Case A” or “Case B”) is applicable. In addition to this web announcement, the EDQM, as a courtesy, will contact CEP holders with details of how to proceed for the dossiers impacted by the revised monograph(s). However, it remains the responsibility of the CEP holder to comply with the requirements of the monograph and if necessary to update their respective applications by the implementation date of the revised monograph at the latest, regardless of whether they have been contacted by the EDQM.

• Case A

The specification of the substance should be updated according to the revised monograph. Unless the CEP holder has made reference to the “current version of the monograph” (without providing details on the Ph. Eur. tests and methods in the CEP application), the updated specification should be included in the next request for revision that is submitted to the EDQM (minor, major or renewal of the certificate) and identified as such at that time (such an update will be free of charge). Where the CEP holder has made reference to the “current version of the monograph”, the revised monograph should be implemented without the need to update the specification of the substance at the next request for revision.

• Case B

This case concerns amendments to the monograph which require the submission of data to the EDQM.

An updated dossier demonstrating that the substance complies with the requirements of the revised monograph should be provided within three months of the EDQM contacting the CEP holder. The company is asked to provide a Module 1 briefly discussing the changes made to the application. This module should also include a clarification on whether all related substances are controlled using only the method described in the revised monograph and whether the substance contains any impurities which are not described in the revised monograph (and which are found above the reporting threshold of the Ph. Eur. general monograph 2034).

Module 3 should be updated to include, as necessary:

• a comparison of the impurity profile of the substance with the updated transparency list of the monograph (3.2.S.3.2 “Impurities”, 3.2.S.4.5 “Justification of Specifications”);
• a discussion on the suitability of the revised monograph to control any impurities which are not described in it;
• an updated substance specification/test methods description (3.2.S.4.1 “Specifications”, 3.2.S.4.2 “Analytical Procedures”);
• certificates of analysis of two batches with reference to the revised monograph (3.2.S.4.4 “Batch Analysis”);
• validation and cross-validation data when an in-house method is used as an alternative to a new test method in the monograph (3.2.S.4.3 “Validation of Analytical Procedures”).

In the “Case B” scenario, CEP applications require an update and therefore any holder of a CEP for a substance in the “Case B” list below is expected to provide the requested information to the EDQM, even if no specific request for information was received (this may happen namely when information regarding a change of contact person has not been submitted to the EDQM in a timely manner).

If the requested information has already been presented in the approved dossier, a simple letter stating this is deemed sufficient.

Failure to update the CEP application and to provide data to the EDQM may challenge the validity of the concerned granted CEP, or delay the ongoing evaluation process of the concerned application.

Upon receipt, data will be reviewed within three months and the CEP holder will be informed of the outcome of the evaluation. The assessment may also result in a revised CEP being granted.

This procedure is free of charge, unless the holder submits, at the same time, a request for other changes.

Note:

The Ph. Eur. monograph for Donepezil hydrochloride monohydrate (3067) is suppressed in Ph. Eur. Suppl. 11.3, as the revised monograph for Donepezil hydrochloride (2582) will cover the anhydrous and monohydrate forms of donepezil hydrochloride. EDQM will provide specific guidance to CEP holders on how this change will be managed by EDQM shortly. No action is required by CEP holders at this time.

NB For monographs classified as “Case B” where the main change concerns the implementation of ICH Q3D, if the CEP is already compliant, it is deemed sufficient to send a simple letter declaring this.

See also:

• CEPs: Background & legal framework
• Certification database
• Certification policy documents & guidelines