EDQM has published the document 《Top ten deficiencies – New Applications for Certificates of Suitability for chemical purity (2015-2016)》 in December, 2016.

This document is a summary of the ten most frequent questions raised after the initial evaluation of new applications for Certificates of Suitability (CEP) for chemical purity. It is based on the content of a sample of 20 deficiency letters sent selected randomly during the second half of 2015 and beginning of 2016.

This document is intended to help applicants to improve the quality of their CEP dossiers and the following top ten deficiencies are to be taken into account while building up the dossier.

Top 1(S.3.2)          Absence or deficient discussion on the risk of having potential mutagenic impurities in the final substance.

Top2(S.2.3)         Absence or insufficient discussion on fate and carryover of related substances of starting materials (included) to the final substance.

Top3(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.

Top4(S.2.3)           Non-acceptable starting materials, necessity to redefine them earlier in the process.

Top5(S.2.3)           Non-adequate or poorly justified specifications in place to control the quality of starting materials.

Top6(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.

Top7(S.3.2)          Non-adequate or missing discussion on carryover of reagents and elemental impurities to the final substance.

Top8(S.2.4)           Non-adequate or poorly justified specifications in place to control the quality of isolated intermediate.

Top9(S.3.2)           Absence or insufficient discussion on fate and carryover of impurities from synthesis intermediates (included) to the final substance.

Top10(S.2.3)         Non-adequate or missing information on the synthesis of starting materials and their manufacturers.

For more details, please refer to the original documents on the EDQM website: https://www.edqm.eu/en/news/top-ten-deficiencies-2015-2016-ceps-chemical-purity .