Limit of Detection and Limit of Quantitation

[kalidassa]

Dear all, if we performing Residual solvent content validation what will be the accepted Limit of Quantitaion for any specified solvents we can give by the validation. generally we are following not more than 50% of specified concentration, is there any ICH Guideline for this, can any one help me.

[krickos]

Hi

Not really, ICH Q2 generaly states:
for the determination of an impurity: from the reporting level of an impurity to 120% of the specification; with a reference to ICH Q3A and B for normal impurities (not PGIs etc) and their expected minimum LOQ/reporting limit.

ICH Q3C do not add to this, however Eu (EMA) has defined what is required to call a residual solvent (mainly class 2 solvents) "not likely to be present" and conseqently be left out of specification. This may have impact on your validation strategy, if you have class 2 solvents earlier in the process and want to omit them from specification you need to go for 10% of the respective ICH Q3C limit i.e 89µg/g for toluene.
If not of interest, 50% of ICH Q3C specification is usually good enough.

Link to EMA annex to ICH Q3C with data requirements:
http://www.ema.europa.eu/docs/en_GB/doc ... 002979.pdf

I like this guidelines because you build your case on the manufacturing process (what goes in where), science (where is redues removed/evaporated) and actual data (confirming the theoretical stuff).

[kalidassa]

Thank you Mr.Krickos