Analytical Methods: A Statistical Perspective on the ICH Q2A and Q2B Guidelines for Validation of Analytical Methods - - BioPharm International

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Analytical Methods: A Statistical Perspective on the ICH Q2A and Q2B Guidelines for Validation of Analytical Methods


BioPharm International
Volume 19, Issue 12


Table 4. Based on the results of the specificity analysis (Table 3), we conclude that the specificity of the assay is 0.2 mg/dL.
The use of standards, product, and spiked excipients for method validation depends on the purpose of the method under test. If National Institute of Standards and Technology (NIST) or World Health Organization (WHO) standards exist for the test method, or if a pharmacopeial method is under consideration, those standards should be used. Standards can be used if the test method requires a standard curve to calculate the response. Bulk drug product or final drug product are used when stability indicating assays are being tested. Stressed samples and time zero samples typically are used for method validation of these stability-indicating assays. When novel proteins or unique products are being tested, typically the only samples that are available are spiked samples. When using spiked samples, one must assume that the spiked value is known without error.

EXAMPLE


Table 5. In this example, the expected range for the assay was 50–150% of the nominal value. Results from using two analysts, each testing five samples three times per day for two days.
The following example shows how specificity analysis would be conducted using the above protocol. Using four samples each with six repeats, an equivocal zone of 0.375 to 0.465 would be used to determine if there are differences among the four levels of analyte. For each level, one would compute the 95% confidence interval and compare it to the equivocal zone. Table 3 shows the results. Based upon those results, we conclude that the specificity of the assay is 0.2 mg/dL (Table 4).


Table 6. A typical accuracy analysis
The validation of linearity, accuracy precision, and range was performed on a cell-based bioassay that did not require a level of quantification or level of detection. The expected range for the assay was 50–150% of the nominal value. Using two analysts, each testing five samples three times per day for two days yielded the results in Table 5.


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