Revisions & Renewals

Each time a revised or renewed CEP is granted, the Holder of the CEP shall give a copy of the CEP to all their customers to allow them to update MA for medicinal products referring to it. The list of valid CEPs is available on this site (see under Databases) and is updated daily.

New system for revision/renewal of CEPs

The system for revision/renewal of CEPs will change for all requests for revision received from 1st July 2008. The main change to the system is that minor revisions to the Certification dossier, which do not cover a change in the specification of the final substance and which do not affect the content of the CEP, will not lead to the revision of the CEP after approval. To allow this modification, the minor change coded R3 has been split into two separate variations.
The following documents have been revised accordingly, and several other clarifications have been introduced:

• Guideline on revision/renewal of certificates of suitability to the monographs of the European Pharmacopoeia (PA/PH/CEP (04) 2 3R)
• Procedures for management of revisions/renewals of certificates of suitability to the monographs of the European Pharmacopoeia (PA/PH/Exp. CEP/T (04) 18)
  
• Application form for revision/renewal.

Notice to holders of CEPs for heparin or enoxaparin

Following the adverse events observed recently in the United States of America and in Europe, and following the measures taken by European Authorities, the EDQM has published a notice to the attention of holders of CEPs for heparin or enoxaparin. More information...

Note for the Attention of Applicants regarding Declarations related to R4 and R6 changes

According to the Guideline on requirements for revision/renewal of Certificates, the condition to apply for a minor revision related to a change or addition of a manufacturer of a starting material or intermediate (R4) or to a change or addition of a manufacturing site (R6) is that the route of synthesis of the concerned materials should be exactly the same as that already approved – including all solvents, reagents, catalysts, raw materials, starting materials and intermediates (including the culture broth and precursors for fermented products). When the route of synthesis of the concerned materials is modified, a request for a major revision should be submitted. More information....

Guide on how to prepare a good revision/renewal dossier now available.

A guide on the preparation of dossiers for revision and renewal is now available. For more information, click HERE.

Electronic submissions

Applicants are encouraged to submit electronic versions of their applications, in addition to paper copies.  This will allow a better and more efficient management of the applications. For more information, please click HERE.

Revisions

Content of the Dossier

The holder of a CEP must inform the EDQM of any change(s) in the information provided in the certification dossier. Changes or revisions are classified into three categories: notifications, minor changes and major changes, depending on the potential impact of the change on the quality of the final substance. 
These three categories correspond to those described in the European regulation on variations 2003/1084/EC and 2003/1085/EC as amended.
Please refer to the 'Guideline on requirements for revision/renewal of certificates: PA/PH/CEP (04) 2 3R', which describes the classification of the changes, the conditions to be met and the documentation to be provided for each type of revision of certificate. The document 'Procedures for management of revisions/renewals of certificates: PA/PH/Exp CEP/T (04) 18 1R' describes the operating procedures for the handling of revisions, fee and timetables.

Submitting a Revision Application

Applicants are encouraged to submit electronic versions of their applications, in addition to paper copies.  This will allow a better and more efficient management of the applications. For more information, please click HERE.

The holder of a CEP must inform the EDQM of any change(s) by sending all the necessary documents demonstrating that the conditions laid down in the present guideline are met. An applicant should send the following documentation to the EDQM:

• a completed application form including the fee form, and
• a single copy of a dossier (preferably in English).
  

Applications to the EDQM consist of a justification of the change and documentation in support of the request as described in PA/PH/CEP (04) 2 3R. Several changes may be submitted at any one time, up to a limit of 3. For any particular scheme, please contact EDQM prior submitting an application.

The revision application is sent to the Certification Division of the EDQM.  It is validated or rejected and then listed for assessment.  After it is assessed, the EDQM may send queries to the applicant. When the queries have been resolved, the EDQM sends the applicant a CEP.

Renewals

Content of the Dossier

A CEP is valid for 5 years from the date of first issuing and is renewed only once. This is consistent with the requirements for a marketing authorisation (MA) stipulated in the revised Directives 2001/82/EC and 2001/83/EC. Once renewed, the CEP is valid for an unlimited period unless it is decided by the EDQM and upon justified grounds, to request one additional renewal (as forseen by Directives 2004/27/EC and 2004/28/EC).
This policy applies to all CEPs for which the date of renewal is from 1 January 2006. For those CEPs which have already been renewed, a new renewal is not necessary provided the dossier is in compliance with the current legislation.  The document 'Procedures for management of revisions/renewals of certificates: PA/PH/Exp CEP/T (04) 18 1R' describes the operating procedures for the handling of renewals.

Submitting a Renewal Application

Applicants are encouraged to submit electronic versions of their applications, in addition to paper copies.  This will allow a better and more efficient management of the applications. For more information, please click HERE.
The request for renewal should be submitted 6 months before the expiry date.  Any requests sent later may lead to a gap between the expiry date of the certificate and the approval of the request for renewal, during which no valid certificate would be available.  Holders have no longer the possibility to include major changes to the content of the dossier at the time of the renewal. Only minor updates of the dossier will therefore be accepted and assessed for renewal.
Provisional certificates are granted at expiry date if the request is not yet approved. They avoid a gap between expiry date and the granting of the renewed CEP. For more information, click HERE.

Compliance with the current regulation

The CEP holder should check that their dossier is in compliance with current legal requirements and update it if necessary, taking in account the following requirements:
- For a CEP referring to the chemical purity
The general chapter 5.10 'Control of impurities in substances for pharmaceutical use' should be used and the specification of the final substance should include appropriate limits for impurities in compliance with the general monograph 2034, 'Substances for pharmaceutical use'.
Should the dossier refer to a monograph, which includes a non-quantitative test for related substances (such as TLC), and which is therefore not in compliance with the requirements of the 'General monograph 2034', the dossier should be updated with another, suitable quantitative method for related substances. This method should be properly validated with regards to the impurity profile of the substance.
- For a CEP referring to TSE risk
Compliance with the current, revised general chapter 5.2.8 'Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary products' should be verified.