Good day everybody.
I have query about different between “quantitative tests for impurities’ content and limit tests for the control of impurities”. If I’m not mistaken the validation parameters used for both are different. How we differentiate between quantitative and qualitative test for impurities. Hope somebody can help me. Regards
Dear Yatt,
Words “Quantitative”- provides the exact figure of the amount of impurities present in the sample
Qualitative -provides whether the impurity is above or below the predetermined arbitary figure
Qualitative type of tests comes under Limit tests of Category II as per
Q2(R1) ICH guideline. Recomendations are Specificity & LOD.
[quote=yatt]Good day everybody.
I have query about different between “quantitative tests for impurities’ content and limit tests for the control of impurities”. If I’m not mistaken the validation parameters used for both are different. How we differentiate between quantitative and qualitative test for impurities. Hope somebody can help me. Regards[/quote]
Dear Yatt,
If the impurity is known, so it must be quantatively analyze and if impurity is unknown so you may qualitatively analyze.
Regards,
[quote=Shahnawaz]Dear Yatt,
If the impurity is known, so it must be quantatively analyze and if impurity is unknown so you may qualitatively analyze.
Regards,[/quote]
Dear Shahnawaz,
I don’t think it is always the case that known impurity should be quantified. If a potential impurity is confirmed by a chromatographic method to be far less than the official limit in lots of batches, why should the method have quantitation capability? In this case limit capability is enough I think.
‘In the chromatogram obtained from Sample Preparation, the area of any peak corresponding to “related subs” is not greater than the area of the peak in the chromatogram obtained from Standard Preparation.’
Above clause is consider quantitative or qualitative? If quantitative the parameter need to be test just Specificty and LOD. It is true?
[quote=crystalover]Dear Shahnawaz,
I don’t think it is always the case that known impurity should be quantified. If a potential impurity is confirmed by a chromatographic method to be far less than the official limit in lots of batches, why should the method have quantitation capability? In this case limit capability is enough I think.[/quote]
It is a better practices that company should have known impurities standard and may quanitified time to time, may have skip test policy on impurities quantification.
Regards,
Dear All,
I would like to know what is the procedure/guideline to be followed to establish “Below Disregard Limit” for related substances by HPLC method.
Your inputs are very appreciated.
Thanks in advance.
T.Nageshwar
Bruce Neagle
While the validation requirements for impurities must comply with ICH QR1 they must also meet the requirements of ICH QR2. The stability guidelines also state that the quantitation limits must be not less than 0.05% wgt/wgt of the target potency of the API in the dosage form. Not an easy act to follow since the impurity profile is dependent on the manufacturing process. Your eventual
Always remember that the Quntitation limit(QL or LOQ) should be less than the reporting threshold.
Try to optimise your analytical method to get the LOQ below 0.05% by treating 0.05% is the reporting threshold for many instances as a worst case.
Regards,
Bujji Kanchi.
Dear Sir,
Am in the process of designing validation protocol and in reference I couldnot able to find the acceptance criteria’s for all the validation prarameters.
I request that can some one give me the information regarding the acceptance criteria and limits for analytical method validation parameters.
Also please send the link of reference, where these limits are mentioned?? whether it is from ICH, FDA or from WHO like that.
I hope my question is clear.
[attach]537[/attach]
Please see the attachment of the section precision and accuracy.
you can find the limits.
Component measured in sample Precision
10.0% ≤ 2%
1.0 up to 10.0% ≤ 5%
0.1 up to 1.0% ≤ 10%
< 0.1% ≤ 20%
Its an australian guideline for analytical method validation
Best Regards,
Bujji Reddy Kanchi.
+91-9676749937
gl_69_analytical_methods.pdf (169.3 KB)
[quote=bujjikanchi][attach]537[/attach]
Please see the attachment of the section precision and accuracy.
you can find the limits.
Component measured in sample Precision
10.0% ≤ 2%
1.0 up to 10.0% ≤ 5%
0.1 up to 1.0% ≤ 10%
< 0.1% ≤ 20%
Its an australian guideline for analytical method validation
Best Regards,
Bujji Reddy Kanchi.
+91-9676749937[/quote]
Yes, I’ve seen those guidelines before (and none from USP or FDA except ORA.LAB.5.4.5 which states 97-103% accuracy for APIs, and 95 to 105% for finished dosage forms) on stuff less than 0.1%. And my supervisor says that source is from Australian Veterinary Pharma, so it’s “Who they?”
ORA.LAB.5.4.5 states “If acceptance criteria are not met, due to situations described in this paragraph, the occurrence should be evaluated in the form of a discussion between analyst(s), lab managers, and QA managers, with the purpose of the analysis and the requirements of the customer being taken into account. The specified acceptance criteria can then be modified, if sufficiently justified.”
So again, no real clear guidance from official documents.
Bujji Reddy Kanchi: can you supply a published source that details that USP or FDA accepts the limits that are listed in the Australian Pharma? We’ve been basically “sitting” on vastly improved technology for an impurity in products because supervisor will not agree to limits wider than we use for finished OTC pharmaceuticals (95-105% recovery, RSD = 2%).