EDQM FAQs
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For any in-house analytical procedure, if the associated method is suitably described by an appropriate general chapter in the “Methods of analysis” section of the Ph. Eur., the reference of the chapter can be given.
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It is possible to quote general chapters such as chapter 2.4.24. Identification and control of residual solvents indicating the system and sample preparation applied or 2.9.34. Bulk density of powders indicating which method (e.g. method 1) since this chapter describes several.
General chapters such as 2.2.29. Liquid chromatography should not be quoted since they only give general information on the analytical technique.
In the event that impurities which are not listed in the Ph. Eur. monograph are controlled in the substance, an officially accepted chemical name of the compound should be used (in-house code may be added if relevant).
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Example of presentation of specification in a CEP dossier in section 3.2.S.4.1:
Quality attributes | Acceptance criteria | Reference of analytical procedures |
Characters | White or almost white, crystalline powder | Substance monograph from Ph. Eur. current Ed. |
Solubility | Practically insoluble in water, slightly soluble in anhydrous ethanol and in methylene chloride. | Substance monograph from Ph. Eur. current Ed. |
Identification Test A (IR) | Complies with reference spectrum | Substance monograph from Ph. Eur. current Ed. |
Specific optical rotation | +158° to + 167° | Substance monograph from Ph. Eur. current Ed. |
Sulfated ash | Not more than 0.1% | Substance monograph from Ph. Eur. current Ed. |
Loss on drying | Not more than 0.5% | Substance monograph from Ph. Eur. current Ed. |
Related substances (by HPLC) | Substance monograph from Ph. Eur. current Ed. | |
Impurity A | Not more than 0.5% | |
Impurity B | Not more than 0.3% | |
Impurity C | Not more than 0.15% | |
Impurity D | Not more than 0.15% | |
Unspecified impurities | Not more than 0.10% | |
Total | Not more than 1.5% | |
Assay (by titration) | From not less than 99.0% to not more than 101.0% | Substance monograph from Ph. Eur. current Ed. |
Residual solvents (by GC) | Ph. Eur. 2.4.24, system B, sample preparation 2 | |
Ethanol | Not more than 5000 ppm | |
N,N-dimethylformamide | Not more than 880 ppm | |
N-Nitrosodimethylamine (NDMA) (by GC-MS)* | Not more than 3.0 ppm | In-house |
Particle size distribution (by laser light diffraction) | D(0.9) not more than 15 μm D(0.5) between 2 μm and 8 μm D(0.1) not more than 2 μm | In-house |
* tested in one batch out of ten
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Despite this, if a CEP applicant/holder decides to include quality attributes that are intended to satisfy a regulatory requirement in another region (i.e. non-European regional requirement) in their specification, they should present them separately (e.g. in an additional table) and identify them accordingly as shown below:
Specification parameters not necessary to satisfy European regional requirements | ||
Assay (by titration) | 99.0% to 101.0% | USP |
Heavy metals | ≤ 10 ppm | Ph. Eur. 2.4.8 |
Water content (by KF) | ≤ 0.5% | JP |
This approach helps maintain clarity and avoids unnecessary burden during evaluation of the CEP application and eases lifecycle management and the use of the CEP.
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