Analytical Test Method Validation - Precision and Accuracy

demonstrated by performing 3 replicates each of three separate sample concentrations (9
determinations) covering the specified range of these procedures.
- Recommended Repeatability Data:
Calculate the result for each replicate. The % RSD for each level should meet the recommended
criteria.
- uggested Repeatability Criteria:
Several factors should be considered when selecting criteria: The intended purpose of the test and
the expected specification range are important parameters. It is recommended that acceptance
criteria be established as recommended in Table 1 and Table 2.
Intermediate Precision:
Intermediate precision expresses 􀂳within laboratories􀂴 variations (e.g., different days, different
analysts and different equipment).
The extent to which intermediate precision may be established depends on the circumstances
under which the procedure is intended to be used. It is suggested that sites establish the effects of
critical random events on the precision of the analytical test procedure.
Typical variations to be studied include days, analysts, equipment, etc. ICH does not consider it
necessary to study these effects individually and this is endorsed by this guideline.
The use of an experimental design (matrix) is considered useful. Certain markets (i.e. Japan)
have more specific requirements for intermediate precision. To meet intermediate precision
requirements for Japan for assay and quantitative impurity procedures, it is recommended that
the analyses be carried out as prescribed by the method over a minimum of six occasions with at
least three analyses per occasion.
An example of such a matrix for Japanese markets is provided in the following table:
Occurrence
#1 Occur #2 Occur#3 Occur #4 Occur.#5 Occur
#6
Day 1 1 2 2 3 3
Analyst 1 2 2 1 1 2
Instrument 1 2 1 2 1 2
Column 1 2 1 2 2 1
Analyses can be carried out using either samples spiked at a suitable level(s) and/or representative
lots containing a representative amount of impurities. If the representative lots do not contain
specified impurities/degradation products, spike studies should be performed. In cases where
specified impurities/degradation products are not available a surrogate material such as a
compound with similar structure or API may be used to demonstrate precision. In these cases, a
rationale for the use of a surrogate should be given.
Recommended Intermediate Precision Data:
Intermediate Precision: Calculate overall % RSD of the multiple occasions. The overall SD or
RSD of the multiple occasions should meet the recommended criteria.