Q&A ON VALIDATION OF ANALYTICAL PROCEDURES – ICH Q2 GUIDELINE PART -5

Q&A ON VALIDATION OF ANALYTICAL PROCEDURES – ICH Q2 GUIDELINE PART -5

Question 1:

How is the specified range determined in an analytical procedure?

Answer 1:

The specified range in an analytical procedure is typically derived from linearity studies and depends on the intended application of the procedure. It is established by confirming that the analytical procedure provides an acceptable degree of linearity, accuracy, and precision when applied to samples containing amounts of analyte within or at the extremes of the specified range.

Question 2:

What are the minimum specified ranges recommended for different types of analyses?

Answer 2:

The minimum specified ranges recommended for different types of analyses are as follows:

For the assay of a drug substance or a finished (drug) product: normally from 80 to 120 percent of the test concentration.

For content uniformity: covering a minimum of 70 to 130 percent of the test concentration, unless a wider, more appropriate range is justified based on the nature of the dosage form.

For dissolution testing: +/-20% over the specified range.

For the determination of an impurity: from the reporting level of an impurity to 120% of the specification.

Question 3:

How is the validated range determined for a controlled release product in dissolution testing?

Answer 3:

For a controlled release product in dissolution testing, the validated range would cover 0-110% of the label claim if the specifications cover a region from 20% after 1 hour up to 90% after 24 hours.

Question 4:

What considerations are mentioned for impurities known to produce toxic or unexpected pharmacological effects?

Answer 4:

For impurities known to produce toxic or unexpected pharmacological effects, the detection/quantitation limit should be commensurate with the level at which the impurities must be controlled.

Question 5:

What is the recommendation for linearity if assay and purity are performed together as one test using only a 100% standard?

Answer 5:

If assay and purity are performed together as one test using only a 100% standard, linearity should cover the range from the reporting level of the impurities to 120% of the assay specification.

Question 6:

How should accuracy be established in an analytical procedure?

Answer 6:

Accuracy should be established across the specified range of the analytical procedure.

Question 7:

What are the methods available for determining accuracy in the assay of the drug substance?

Answer 7:

Several methods are available for determining accuracy in the assay of the drug substance:

1. a) Applying the analytical procedure to an analyte of known purity (e.g., reference material).
2. b) Comparing the results of the proposed analytical procedure with those of a second well-characterized procedure with stated accuracy (independent procedure).
3. c) Inferring accuracy once precision, linearity, and specificity have been established.

Question 8:

How can accuracy be determined in the assay of the drug product?

Answer 8:

Several methods are available for determining accuracy in the assay of the drug product:

1. a) Applying the analytical procedure to synthetic mixtures of the drug product components with known quantities of the drug substance.
2. b) Adding known quantities of the analyte to the drug product if obtaining samples of all components is impossible, or comparing results with a well-characterized procedure (independent procedure).
3. c) Inferring accuracy once precision, linearity, and specificity have been established.

Question 9:

What approach can be taken if it’s impossible to obtain samples of all drug product components for determining accuracy?

Answer 9:

If obtaining samples of all drug product components is impossible, it may be acceptable to either add known quantities of the analyte to the drug product or compare results with a second, well-characterized procedure with stated accuracy (independent procedure).

Question 10:

When can accuracy be inferred in an analytical procedure?

Answer 10:

Accuracy may be inferred once precision, linearity, and specificity have been established in the analytical procedure.