impurities and LOQ

[vijayassi]

Dear all,

please any one clarify regarding LOQ limit of impurity

one of the impurity having LOQ more than reporting threshold and 50% below of its specification level,
is it acceptable ?

pls clarify and provide guideline evidence.

thanks and regards
Kumar

[tom jupille]

No guidance required. The LOQ must be below the reporting level (otherwise, how will you know whether or not to report the impurity).

[gtma]

I agree with Tom. I had a unique situation where the known impuritiy-L elute in a noisy region (early part) of the chromatogram where its LOQ was higher (e.g. 0.20%) than the "overall" method's LOQ (e.g. 0.1%).....gradient method. No unknown impurities (in stressed and stability samples) elute in this region where the Impurity-L elutes. I believe it's okay to provide a rationale for accepting a method with this unique situation. If the impurities are all known and have specifications, would it be acceptable to have a higher LOQ (e.g. 0.20%) than the ICH reporting limit (e.g. 0.10%)......spec (e.g. 0.4%)? We should strive to develop better methods .

[vijayassi]

Thank you TOM and GTMA .

gtma, please provide guideline evidence for known impurity LOQ more than reporting threshold is acceptable
(below 50% of its specification limit)

regards
kumar

[gtma]

Sorry, I don't have any guideline evidence. It's seem logical that for known impurities with a specification, it makes sense to validate from 50% to 150% of specification in some cases. For example, if the known impurity specification is 1.0% and the ICH reporting limit is 0.10%, should I validate from LOQ to 150% of spec or 50% to 150%? I think it's acceptable to validate from 50% to 150% of spec if that known impurity is not part of the total impurities. However, if the known impurity is included in the total impurities or used as a surrogate for unknown impurities, then I would recommend validating from the LOQ/ICH reporting to 150% of spec. Any thoughts?