Dear Forum,
Cleaning Method (HPLC) validation completed for one of our product by considering specification limit as 0.4ppm unfortunately actual spec limit 4ppm). Now we want prepare specification with limit 4ppm, MOA same as done in method validation.
for this, whether we have to perform again method validation by considering specification limit 4ppm ??? Or not required.
the same method validation can support the 4ppm specification limit???
Thanks in advance…
regards
svr
Dear SVR,
As part of linearity studies, you might study up to 0.48 ppm (120% of your assumed value). But, you have to prove the linearity from LOQ to 120% of 4 ppm (minimum five concentrations). Regulators may not accept you practice. Better you should go for revalidation. If it is not possible to conduct the complete validation, at least prove the linearity and range of your test method (from LoQ level to 120%.)
Regards
Veerraju
Dear raju,
Linearity varies more at lower concentrations than high concentrations, then what is the need for go upto 120% of specification / 4ppm during linearity study???
Why the range is required during the method validations? we didnot perform the same… if required then kindly elaborate the same…
Regards
svr
[QUOTE=ramyaraj725]Dear SVR,
As part of linearity studies, you might study up to 0.48 ppm (120% of your assumed value). But, you have to prove the linearity from LOQ to 120% of 4 ppm (minimum five concentrations). Regulators may not accept you practice. Better you should go for revalidation. If it is not possible to conduct the complete validation, at least prove the linearity and range of your test method (from LoQ level to 120%.)
Regards
Veerraju[/quote]
According to ICH Q2…
A linear relationship should be evaluated across the range of the analytical procedure
The specified range for the determination of an impurity is from the reporting level u to 120%[/u] of the specification;
Accuracy should be assessed using a minimum of 9 determinations over a minimum of 3 concentration levels covering the specified range (e.g., 3 concentrations / 3 replicates each of the total analytical procedure).
By consolidating the above three statements, for determination on an impurity (say contaminant in our cleaning validation), linearity should be proved from at least LOQ to 120%
Actually, in my previous reply, I suppose to say “at least prove the linearity and accuracy”
And, why range not required? As per ICH Q2, for impurity quantification test, you should prove the range of an analytical procedure. Though no need to conduct any specific study as part range study, you have to define the range of your analytical procedure based on you linearity, accuracy and precision studies.
Regards
Veerraju