EDQM Regulatory Update PA/PH/CEP (14) 06, 2R: Guidance on Using an Intermediate CEP in a Final Substance CEP Application
The revised EDQM Regulatory Update PA/PH/CEP (14) 06, 2R guideline clarifies how a valid Certificate of Suitability (CEP) for an intermediate (CEP X) can support a CEP application for a final substance (CEP Y). The guidance reflects CEP 2.0 principles and is applicable from September 2026.
Key Requirements for Using CEP X in CEP Y
CEP X must be valid and must cover exactly the Ph. Eur. grade intermediate used in the manufacturing process of CEP Y. A copy of CEP X should be included in section 3.2.S.2.4. For CEP 2.0 or hybrid CEPs, the relevant Letter of Access should also be provided.
The complete specification approved under CEP X should be applied to the intermediate in CEP Y. Any deviation or exception should be supported by an appropriate scientific justification and accepted by the relevant authority.
Avoiding Duplication of Manufacturing Information
Manufacturing information already adequately covered by CEP X generally does not need to be repeated in CEP Y sections 3.2.S.2.2, 3.2.S.2.3 and 3.2.S.2.4. This can help reduce regulatory duplication and streamline CEP submissions.
Impurity and Quality Risk Assessment
Although CEP X can reduce the need to repeat manufacturing details, CEP Y remains responsible for its own impurity carry-over and due diligence assessment. This is particularly important where impurity specifications or control strategies differ. Nitrosamine and elemental impurity risks associated with CEP X must also be considered as part of the CEP Y assessment.
Manufacturing Sites and Lifecycle Management
For supply-chain transparency, all manufacturing sites covered by CEP X should be identified in CEP Y. If CEP X is revised, suspended, withdrawn, or expires, the impact on CEP Y must be assessed and CEP Y should be appropriately revised where necessary.
Multiple CEPs for an Intermediate
The revised guidance also allows more than one CEP to be used for an intermediate, provided the relevant manufacturing processes are not substantially different.
Regulatory Impact
The revised guidance enables applicants to leverage an existing intermediate CEP while avoiding unnecessary duplication of manufacturing information. However, CEP Y remains responsible for appropriate impurity, nitrosamine, elemental impurity, due diligence, and lifecycle assessments.
Implementation: September 2026
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