Commonly Deficient Issues When Applying For A Certificate of Suitability (CEP)

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.

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 EMA/CHMP/SWP/251344/2006.
  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.

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.