Q&A ON VALIDATION OF ANALYTICAL PROCEDURES – ICH Q2 GUIDELINE PART -6
Question 1:
How should accuracy be assessed in the quantitation of impurities?
Answer 1:
Accuracy should be assessed on samples (drug substance/drug product) spiked with known amounts of impurities.
Question 2:
What is considered acceptable when it is impossible to obtain samples of certain impurities and/or degradation products for assessing accuracy?
Answer 2:
When it is impossible to obtain samples of certain impurities and/or degradation products, it is considered acceptable to compare results obtained by an independent procedure. The response factor of the drug substance can be used.
Question 3:
How should individual or total impurities be determined, and what parameters should be considered?
Answer 3:
It should be clear how the individual or total impurities are to be determined, such as weight/weight or area percent, in all cases with respect to the major analyte.
Question 4:
What is the recommended approach for assessing accuracy, and what are the minimum requirements?
Answer 4:
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).
Question 5:
How should accuracy be reported in the quantitation of impurities?
Answer 5:
Accuracy should be reported as percent recovery by the assay of known added amount of analyte in the sample or as the difference between the mean and the accepted true value together with the confidence intervals.
Question 6:
What is included in the investigation of precision for tests concerning assay and quantitative determination of impurities?
Answer 6:
The investigation of precision for tests concerning assay and quantitative determination of impurities includes an assessment of repeatability, intermediate precision, and reproducibility.
Question 7:
How should repeatability be assessed?
Answer 7:
Repeatability should be assessed using either a minimum of 9 determinations covering the specified range for the procedure (e.g., 3 concentrations/3 replicates each) or a minimum of 6 determinations at 100% of the test concentration.
Question 8:
What factors should be considered when establishing intermediate precision?
Answer 8:
The extent to which intermediate precision should be established depends on the circumstances under which the procedure is intended to be used. The effects of random events on the precision of the analytical procedure should be established, including variations such as days, analysts, equipment, etc. It is encouraged to use an experimental design (matrix) to study these effects.
Question 9:
How is reproducibility assessed?
Answer 9:
Reproducibility is assessed by means of an inter-laboratory trial, particularly in cases of standardization of an analytical procedure, such as for inclusion in pharmacopoeias. However, these data are not part of the marketing authorization dossier.
Question 10:
What data should be reported for each type of precision investigated?
Answer 10:
The standard deviation, relative standard deviation (coefficient of variation), and confidence interval should be reported for each type of precision investigated.