Chemical purity regulatory findings

New Applications for Certificates of Suitability (CEP) for chemical purity (Top 10 deficiencies)

The EDQM has issued a document that summarises the ten most frequent questions raised after the initial evaluation of new applications for Certificates of suitability (CEP) for chemical purity.

In the document, the top ten most frequent questions are listed together with expectations and recommendations on how to address the specific deficiencies, with reference to applicable guidelines.

This document is intended to help applicants to improve the quality of their dossiers, in order to facilitate and speed up the granting of their CEPs. The information should be taken into account while building up a dossier, in combination with the EDQM Guideline “Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 04 1)” available on the EDQM website.

The top 10 deficiencies are:

1. Absence or deficient discussion on the risk of having potential mutagenic impurities in the final substance.
2. Absence or insufficient discussion on fate and carryover of related substances of starting materials (included) to the final substance.
3. Lack of details and/or poor description of the manufacturing process of the substance from the introduction of starting materials
4. Non-acceptable starting materials, necessity to redefine them earlier in the process.
5. Non-adequate or poorly justified specifications in place to control the quality of starting materials
6. 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.
7. Non-adequate or missing discussion on carryover of reagents and elemental impurities to the final substance.
8. Non-adequate or poorly justified specifications in place to control the quality of isolated intermediate.
9. Absence or insufficient discussion on fate and carryover of impurities from synthetic intermediates (included) to the final substance.
10. Non-adequate or missing information on the synthesis of starting materials and their manufacturers

For further details see EDQM: https://www.edqm.eu/sites/default/files/cep_to_monographs_of_pheur_march2017.pdf

Posted by Dr. Tim Sandle