In January 2024, the European Medicines Agency (EMA) published a Q&A document entitled "How to use a CEP in the context of a Marketing Authorisation Application (MAA) or a Marketing Authorisation Variation (MAV)", which contains detailed recommendations for the content of an authorisation dossier when a CEP represents the active substance documentation. Special cases (e.g. in the case of sterile active substances) and life cycle considerations are also addressed.

Link: https://www.ema.europa.eu/en/questions-answers-how-use-cep-context-marketing-authorisation-application-or-marketing-authorisation-variation

Stability data: A frequently observed deficiency concerns the lack of presentation of stability data in cases where no re-test period is indicated on the CEP. In this context, applicants are advised to submit their own stability data for the active substance in accordance with the relevant stability guidelines in the corresponding section of the dossier.

Impurities: Applicants are responsible for obtaining sufficient information on actual and potential impurities of the active substance from the CEP holder in order to establish an adequate active substance specification. Product-specific relevant information, in particular on elemental impurities and nitrosamine impurities, should be mapped in section 3.2.P.5.5/5.6 if necessary.

Furthermore, attention is drawn to the fact that the limit values and control strategy for impurities established by the EDQM within the framework of the CEP assessment are based on the maximum daily dose and the route of administration of the active substance in already authorised medicinal products. Therefore, applicants are required to assess the appropriateness of the limits and control strategy for their product and its specific indications, duration of therapy and maximum daily dose.

CEP subtitle: Any aspects of active substance quality that are not covered by the CEP and are also relevant to the finished product must be addressed by the applicant in the dossier. For example, if a CEP does not contain a subtitle for micronisation(micronised), then this aspect was not taken into account when the CEP was issued. Therefore, the applicant must generate their own relevant data (see EMA Q&A document above) and file it in the relevant sections of the dossier if the applicant intends to use the active substance in micronised form in the finished product.

Heparins: In the case of heparins and heparin derivatives, which are classified as biological products, complete active substance documentation is expected in the dossier for new authorisations and variation applications, as this cannot be replaced by a CEP. For products that use an old CEP that has not been revoked by the EDQM, complete documentation is expected to be submitted in Module 3 in the event of a dossier update. Confirmation that this documentation corresponds to the CEP dossier assessed by the EDQM must be enclosed.

The CEP 2.0 was created by the EDQM with the aim of ensuring improved user-friendliness and increased transparency of the relevant information without increasing the regulatory burden. In addition to a number of technical and regulatory adjustments, changes have also been made to the content, including the information presented on the CEP 2.0 regarding the control of the active substance. For example, the specification of the CEP holder (in accordance with section 3.2.S.4.1) or the quality of the water in the final steps of the synthesis are now also stated on the CEP.

The EDQM maintains a comprehensive FAQ page that contains further information on the CEP 2.0: faq.edqm.eu/display/FAQS/CERTIFICATION+OF+SUBSTANCES+FOR+PHARMACEUTICAL+USE