When can a CEP be withdrawn?

Recommendation

23-25 April 2024
Barcelona, Spain

Global Registration and Life Cycle Management for APIs

The temporary suspension of a CEP, its definitive withdrawal, or the closure of an ongoing application procedure for a CEP follow strict rules defined by the EDQM and recently published in a document entitled "Suspension or withdrawal of a Certificate of Suitability, closure of an application". In addition to the definitions of the key notions, the document contains a precise description of the scenarios which lead to the suspension or the withdrawal of a CEP, and/ or to the closure of an application procedure. Moreover, the document presents the specifications for decision-making, the communication channels and the committees involved.

The terms "Suspension" and "Withdrawal" tend to be frequently confused. The definitions contained in the document should clarify ambiguities. According to the definitions:

• The "Suspension" of a CEP is limited to a period of 2 years. It may be requested by the holder of a CEP or be the result of a decision taken by the EDQM. A suspended CEP may be restored if the holder of the CEP actively applies for it and submits the corresponding information. If not, or if he/ she doesn't submit the documents required, the CEP will be automatically withdrawn.
• A "Withdrawal" is a definitive cancellation of a CEP. A CEP that has been withdrawn cannot be restored.

The reasons for temporary suspension, definitive withdrawal, or the closure of an ongoing application procedure for a CEP are similar; yet, in case of a "Withdrawal" they are more serious - as described below:

Suspension

• An inspection carried out by the EDQM or by a supervisory authority (GMP inspection) reveals major GMP deficiencies. There may be a potential risk for public health.
• An inspection by the EDQM shows that the manufacturing process doesn't comply with the provisions laid down in the CEP dossier.
• The CEP dossier isn't in compliance anymore with the requirements of the certification procedure. The holder hasn't submitted any information to maintain it.
• The CEP holder requests a suspension; for example because of temporary cessation of production or renovations at the production site. Another reason is: the CEP holder needs time for the manufacture of an API to meet the requirements of a revised Ph.Eur. monograph.

Withdrawal

• An inspection by the EDQM shows urgent action needed because of risk for public health or extensive and systemic falsifications were found in documents and data.
• The company refuses the inspection, requests the discontinuation, or delays, i.e. restricts the access to certain areas or documents.
• The CEP holder doesn't actively lift the suspension of the CEP.
• The CEP dossier isn't in compliance anymore with the requirements of the certification procedure, and the holder hasn't submitted any information to maintain it.
• The CEP holder doesn't exist any longer, or the production of the API has ceased without informing the EDQM.
• The CEP holder requests the withdrawal of a CEP, e.g. because of cessation of production, or closure of the site.

Closure of a CEP application

• An inspection carried out by the EDQM or by a supervisory authority (GMP inspection) reveals major GMP deficiencies. There may be a potential risk for public health.
• The company refuses to be inspected.
• The reply to the EDQM's deficiency letter by the CEP holder is insufficient or not provided in time.
• The CEP holder requests the closure of the application procedure.

EDQM's so-called Ad hoc Committee takes the final decision over the procedures described. It renders its decision two weeks after an inspection or receipt of the withdrawal request by the CEP holder. The committee then communicates its decision to the CEP holder and/ or to the relevant licensing or supervisory authorities. The Ad hoc Committee is supported by an internal decision board. This Internal Decision Board reviews all the documents and opinions and submits proposals to the Ad hoc Committee on the decision to be taken.

A regularly updated list of   "CEP Suspensions, Withdrawals & Restorations" can be found on the EDQM website.

In connection with the new document, the lecture of the following papers is recommended:

• Resolution AP-CSP (07) 1 "Certification of suitability to the monographs of the European Pharmacopoeia". This policy paper from 2007 (bilingual, english-chinese) describes the main features of the certification process. 
• PA/PH/CEP (01) 1, 10R "Terms of Reference".This document gives information about the committees involved in the certification process, their composition and method of working.