EDQM Amends CEP Submission and Revision Process; Starting Materials Remain at Issue; Risk-Based CEP Inspection Approach is Finding Problems

A revised process for amending or renewing certificates of suitability (CEPs) put in place by the European Directorate for the Quality of Medicines and Healthcare (EDQM) mandates that some major changes previously filed as revisions will now require applying for a new CEP.  The revised process went into effect on September 1.

The changes to the procedure and related forms brings EDQM’s CEP revision processes into line with recent changes to the EU variations regulations, including the use of “notification,” “minor” and “major” change categories.  EDQM also follows suit in requiring the submission of comparative tables showing the current practice side-by-side with the proposed change.

As in the past, EDQM recommends that requests for renewal should be submitted six months before a certificate’s expiry date.  It notes that “requests sent later may lead to a gap between the expiry date and the approval of the renewal request,” adding that provisional certificates can be granted if a request has not yet been approved.

A high-level view of the revised requirements and change category definitions are included in a five-page procedure on “management of revisions/renewals of CEPs.”

A companion 22-page guideline on “requirements for revision/renewal of CEPs” lists the types of changes, their associated categorization, and the required documentation for administrative and quality sections of chemical and herbal product CEPS and those for products that may contain TSEs (links to the procedure and guideline are provided below).

CEPs Are Not GMP Certificates

Although the CEP procedure has been in effect for nearly 20 years, what it certifies and how it is used is still subject to misinterpretation – particularly in non-EU countries.

At a conference on the “Current and Emerging EU Regulations and Inspection Trends” co-sponsored by PDA and the Irish Medicines Board (IMB) in Dublin, Ireland in July, EDQM Director Susanne Keitel discussed what the CEP certifies and what it does not.

The CEP “certifies that the quality of a given substance can indeed be suitably controlled by the European Pharmacopeia monograph, and, if necessary, the additional tests which are stated on the CEP,” she explained.  “It does not replace the certificate of analysis. It is a paper-based evaluation, and it does not replace a GMP certificate. It is not a GMP certificate.”

Keitel noted that “if you go to India or China, you might find manufacturers or suppliers who will praise their substance because they are in possession of a CEP, and they will try to sell this as having been approved by EDQM.”  She stressed that this interpretation “is entirely wrong – it has never been the fact.”

[CLICK HERE for the complete story.  Included is an update from EDQM on the starting material issue and CEP inspection results.  Nonsubscribers can purchase the story for $195 by contacting Jonathan Trethowan (jonathan@ipq.org).]

See related IPQ stories:

EDQM’s Efforts to Clarify Starting Material Expectations Include Internal Policy Guide; SM Dialogue Continues

Look Forward, Not Backward, in API Process for Impurity Risks, Industry Experts Urge EU Regulators

IPQ Nov./Dec. 2007 Special Report