EDQM updates Guidelines on the CEP Procedure

Recommendation

22/23 February 2024
Munich, Germany

API Regulatory Starting Materials
Definition, Manufacture, Assessment and handling post-approval Changes

At the end of last year, the EDQM updated the following four guidelines. Those guidelines contain provisions for new applications for a Certificate of Suitability (CEP) as well as for the revision or renewal of a CEP:

• Guideline on requirements for revision/renewal of Certificates of Suitability to the European Pharmacopeia Monographs (PA/PH/CEP (04) 2, 7R corr)
• Guideline on sister files (PA/PH/CEP (09) 141 2R) including application form
• Management of Applications for new Certificates of Suitability and Requests for Revision or Renewal of Certificates of Suitability (PA/PH/CEP (13) 110, 2 R) including application form
• Content of the dossier for chemical purity and microbiological quality (PA/PH/CEP (04) 1, 6R)

You can read here a brief summary of the contents and changes made to the documents:

Guideline on requirements for revision/renewal of Certificates of Suitability to the European Pharmacopeia Monographs

• Inclusion of the change: "Change of starting material manufacturer" with the following change categories
  - Immediate notification (IN): The new manufacturer belongs to the same group.
  - Minor (MIN): The new manufacturer doesn't belong to the same group or the new manufacturer uses a different synthesis route, which has an impact on the specifications of the starting material.
  - Major (MAJ): the new manufacturer uses a different synthesis route or conditions, which means that the specifications of the starting material or the change of manufacturer takes place within the framework of the manufacture of a biological substance.
• Reference to recent regulatory changes, e.g. regarding ICH M7 or the implementation of ICH Q3D in the CEP procedure (possibility to submit a Risk Management Summary).
• Inclusion of further cases in which the revision of an existing CEP is no longer possible but the application for a new separate CEP is necessary (e.g. addition of a further manufacturer for the API that does not belong to the same group or significant change in the synthesis route even if the contamination profile remains unchanged).

Guidance on applications for "sister files"

The "sister file" procedure facilitates the submission of another CEP application for an API for which a CEP has already been issued. The new CEP can, for example, be used for the same API but with an alternative specification. Such application procedures are usually less bureaucratic and can be processed more quickly.
The revised guidance takes into account various cases in which the "sister file" procedure is possible or not and also makes reference to the ICH guidelines Q11 Q&A, Q3D and M7.
There is a new application form for the "sister file" procedure.

Management of Applications for new Certificates of Suitability and Requests for Revision and Renewal of Certificates of Suitability

In this revised guidance, the processing period for a "sister file" procedure was shortened from 3 to 2 months and thus aligned with the processing period for a "major revision". This is the only change in this document. A new application form has also been assigned to it.

Content of the dossier for chemical purity and microbiological quality

This Guideline also takes into account - as does the first Guideline above - cases where a separate application must be submitted, for example when a significantly different synthesis route with otherwise the same impurity profile or different production sites do not belong to the same group. A separate application procedure is also required in the event that raw material is obtained from different sources with different TSE risks. The ICH Q11 Q&A, Q3D and M7 guidelines are also considered in this document.

These updated guidelines have a significant impact on the regulatory strategy of a marketing authorisation procedure. The EDQM therefore strongly recommends that applicants consider them in order to avoid unnecessary delays in the application process.

All four revised Guidelines have been in force since the beginning of 2019.