EDQM discloses top 10 CEP deficiencies
The European Directorate for the Quality of Medicines and Healthcare (EDQM) has published a document detailing the most common questions raised after initial evaluations of Certificates of suitability (CEP) for chemical purity.
The document "is intended to help applicants to improve the quality of their CEP dossiers, in order to facilitate and speed up the granting of their CEPs," according to the EDQM.
The top 10 deficiencies are as follows:
- TOP 1 (S.3.2) Absence or deficient discussion on the risk of having potential mutagenic impurities in the final substance.
- TOP 2 (S.2.3) Absence or insufficient discussion on fate and carryover of related substances of starting materials (included) to the final substance.
- TOP 3 (S.2.2, S.2.4) Lack of details and/or poor description of the manufacturing process of the substance from the introduction of starting materials (synthesis, narrative description, flow charts, recovery and reprocessing procedures). Incongruences noted between information given in section S.2.2 and section S.2.4.
- TOP 4 (S.2.3) Non-acceptable starting materials, necessity to redefine them earlier in the process.
- TOP 5 (S.2.3) Non-adequate or poorly justified specifications in place to control the quality of starting materials.
- TOP 6 (S.2.3) Non-adequate or missing specifications (and analytical methods) for reagents and solvents (recovered and recycled included) used to manufacture the substance from the introduction of starting materials.
- TOP 7 (S.3.2) Non-adequate or missing discussion on carryover of reagents and elemental impurities to the final substance.
- TOP 8 (S.2.4) Non-adequate or poorly justified specifications in place to control the quality of isolated intermediate.
- TOP 9 (S.3.2) Absence or insufficient discussion on fate and carryover of impurities from synthetic intermediates (included) to the final substance.
- TOP 10 (S.2.3) Non-adequate or missing information on the synthesis of starting materials and their manufacturers.
The document - which includes together with expectations and recommendations on how to address the specific deficiencies - should be taken into account in combination with the EDQM Guideline 'Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 04 1)', according to the EDQM.