The CEP of the Future

CEP 2.0: Introduction and Background

The European Directorate for the Quality of Medicines & HealthCare (EDQM) is at the starting point of implementing various changes regarding the procedure and documentation for Certification of suitability to the monographs of the European Pharmacopoeia (CEP). This results in a “new-look” CEP called the “CEP 2.0” and impacts CEP applicants, CEP holders, and CEP users. Therefore, meetings were held on the 11^th and 16^th of May by the EDQM to address more information concerning these changes.

In the EU, the required information on chemistry, manufacturing and control of an active pharmaceutical substance can be submitted in three ways[1]:

• The Applicant can submit full details as part of the marketing authorization application (MAA).
• The active substance manufacturer (or designated ASMF holder) may submit full details via the Active Substance Master File procedure at which the Applicant’s Part needs to be included in the MAA.
• The active substance manufacturer (or designated CEP holder) can submit documentation to the EDQM to evaluate the suitability of the pharmacopeial monograph concerning the manufacturing method used. Additional information and documentation should be included in the MAA, for example, a copy of the current CEP, batch analysis results of the active substance recorded by the Applicant, and stability data to support a retest period if no retest period is mentioned on the CEP.

The latter only applies to existing active substances described in the European Pharmacopeia (Ph. Eur.). In general, a CEP has the advantage of avoiding subsequent reassessment.

The main changes in CEP 2.0

After 30 years of service and in consultation with stakeholders, the EDQM has now redesigned the CEP to increase the user-friendliness and transparency of information. This resulted in a “new-look” CEP called “CEP 2.0”, formerly known as “the CEP of the future”. We want to draw your attention to the following main changes.[2]^,[3]

Specification

The additional controls, such as impurities and solvents previously mentioned on the CEP, will be replaced by an Annex to the CEP showing the specification. The specification should be aligned with what has been assessed. It should therefore contain only information corresponding to the quality claimed. If no specific grade is requested, a corresponding test, such as microbiological controls, particle size, and polymorphism, should not be included.

The CEP dossier should be adapted similarly: it should only contain information corresponding to the quality claimed, and information not assessed and not approved should be deleted.

Analytical procedures

The analytical procedures described in the CEP dossier should be divided into two subsections:

1. In-house analytical procedures that are an alternative and equivalent to Ph. Eur. procedures, and
2. Additional in-house analytical procedures for control of additional impurities or parameters (e.g. particle size distribution) are not included in the individual monograph.

Only the procedures in the second subsection will be enclosed as an Annex to the CEP.

General properties

The CEP dossier should be updated with the maximum daily dose, route of administration and treatment duration on which the control strategy and the specification are based.

Quality of water

The water quality during the last manufacturing steps will be mentioned on the CEP.

Holder’s commitment

To raise awareness, the CEP holder should commit themselves via the updated application form to share pertinent information with their customers.

Company details

The company details (name and address) mentioned on the CEP should be complemented with the EMA SPOR/OMS Organisation (Org) and Location (Loc) ID. These are unique identifiers for organizations and their locations requested and registered via the EMA SPOR/OMS database. Therefore, the relevant CEP Modules should be adapted accordingly.

Declaration of access box

The declaration of access box mentioned on the CEP will be replaced by a separate letter of access.

Numbering system

A revised CEP will no longer be issued for approved changes that do not impact the CEP content, even if it concerns major changes.

Accordingly, a renewed CEP will no longer be issued at the end of the renewal procedure, and the part of the numbering system related to the renewal (i.e. R0 or R1) will be deleted. If changes are introduced at renewal that impact the CEP content, a revised CEP will be issued.

Implementing CEP 2.0 impacts CEP applicants, CEP holders, and CEP users. All changes should be fully implemented for new CEPs and during upcoming renewal procedures. Initially, the changes should be implemented only partly for revisions and notifications. However, at a later stage, all existing CEPs are expected to switch to CEP 2.0.

Implementations start from June 1^st, whether the first CEPs 2.0 are expected to be issued in Q3.

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[1] https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-summary-requirements-active-substances-quality-part-dossier-revision-1_en.pdf, (assessed May 2023).

[2] https://www.edqm.eu/en/what-is-the-cep-2.0, (assessed May 2023).

[3] https://www.edqm.eu/en/-/093-news-requirements-for-the-content-of-the-cep-dossier-according-to-the-cep-2.0-and-updated-application-forms, (assessed May 2023).