What Are The Common Mistakes With CEP’s?

The  Certificate of Suitability or CEP is a certificate issued by the European Directorate for the Quality of Medicines (EDQM) that certifies the compliance of a pharmaceutical substance or active pharmaceutical ingredient (API) with the requirements of the relevant monograph of the European Pharmacopeia and therefore the EU directives for medicines. A list of all CEPs granted is available on the EDQM website.

11 Most Common Mistakes

Many companies encounter a range of issues when applying for a Certificate of Suitability (CEP).  The EDQM have identified a number of areas that arise frequently in CEP applications.  They are:

  1. Carryover of Materials: The carryover of impurities from starting materials into the finished product should be clearly discussed and where applicable a justification of its absence should be provided or appropriate limits should be defined if present.
  2. Starting Materials: The proposed starting material must be justified, if this is not clearly justified the assessor may request a redefinition of the starting material.
  3. Genotoxic Impurities: The presence of genotoxic impurities should be discussed and limits must be set if applicable as per ICH guideline M7.
  4. Comparison of Quality: Where applicable a comparison of the quality of the final substance obtained with starting materials from different suppliers must be provided.
  5. Starting Material Specification: All specifications provided for starting materials must be complete and show mass balance with regards to purity.
  6. Class 1 Solvents: The potential for contamination by class 1 solvents should be addressed were appropriate as per ICH Q3C/Ph. Eur. General chapter 5.4.
  7. Impurities: A discussion must be included on the potential impurities likely to arise from the process and their limits.
  8. Cross Validation: It is expected that cross validation is carried out between the Ph Eur and any in-house methods for the control of related substances. The methodology from ICH Q2B should be used.
  9. Maximum batch size: The batch analysis results presented should reflect the maximum batch size proposed.
  10. Method Suitability: Suitability of the methods of the monograph must be demonstrated for all additional impurities that are present in the material. If all impurities are not suitably controlled a validated method must be supplemented.
  11. Stability: Sufficient Stability data must be presented to justify the proposed re-test period, where applicable as per ICH Q1.

These commonly deficient issues can hold up the issuing of a Certificate of Suitability (CEP) and lead to requests for further clarification.

We look at these issues and others related to CEP’s in our article ‘How To Obtain A Certificate of Suitability (CEP)‘.  You can read it by clicking the link.

Contact Us About Your CEP Needs

Acorn Regulatory can assist you in obtaining a CEP.  Our expert team works on this issue on behalf of a large number of companies on an annual basis.  Contact us today on 00353 52 61 76706 or complete your details below and we will get in touch with you.

About the Author
Christine McGrath
Senior Regulatory Affairs Advisor
Christine McGrath is an experienced Senior Regulatory Affairs Advisor at Acorn Regulatory. She works with companies around the world on issues relating to pharmaceutical regulatory affairs. At present, she is also working with our Clinical team on a groundbreaking veterinary clinical trial. You can read more articles by Christine by clicking the link below.
Other articles by Christine