EDQM Updates Guidance on CEP Sister File Applications

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has published a revised version of its guidance on applications for "sister files": PA PH CEP (09) 141. The original guidance document provided the initial framework for the sister file procedure. It set out the basic principles for submitting and assessing related CEP applications and helped applicants and assessors determine when the procedure could be used.

The update reflects the EDQM's experience with the sister file procedure over many years. Its purpose is to improve the consistent interpretation and application of the procedure, while providing applicants with greater clarity on eligibility, documentation and assessment expectations.

The revised guidance is intended to support:

• a consistent understanding of the sister file procedure;
• the correct classification and evaluation of Certificate of Suitability (CEP) applications;
• greater transparency in the assessment process; and
• equal treatment of applicants.

Clarification of eligibility criteria

One of the most important changes concerns the conditions under which a sister file application may be accepted. In principle, an application may not qualify as a sister file if the proposed manufacturing process involves:

• different intermediates;
• different starting materials;
• different reagents.

However, such an application may still be considered if the applicant can demonstrate that the fundamental chemical principles and reaction mechanisms remain the same as those described in the CEP dossier used as the reference.
This clarification is intended to help applicants assess at an early stage whether the sister file route is appropriate and to ensure that applications are classified consistently.

Extension to sterile substances

The scope of the sister file procedure has also been broadened. Under the revised guidance, CEP applications for sterile substances may now fall within the scope of the procedure. Applications for TSE CEPs, however, remain excluded.

Additional examples and documentation requirements

The revised document includes a wider range of examples describing situations that may be considered acceptable under the sister file procedure. These examples are intended to illustrate how the eligibility criteria should be applied in practice.
In addition, the EDQM has provided further clarification regarding the documentation that applicants are expected to submit in support of a sister file application. This should help applicants prepare more complete submissions and reduce uncertainty during the classification and assessment process.

The revised guidance, PA PH CEP (09) 141, entered into force on 1 September 2026. Applicants planning to use the sister file procedure should review the updated guidance carefully, particularly the revised eligibility criteria and the clarified documentation expectations.