Analytical method validation for FDA complianc.PPT

* * Linearity Ability of an assay to elicit a direct and proportional response to changes in analyte concentration. * 2009 Linearity Should be Evaluated By Visual Inspection of plot of signals vs. analyte concentration By Appropriate statistical methods Linear Regression (y = mx + b) Correlation Coefficient, y-intercept (b), slope (m) Acceptance criteria: Linear regression r2 0.95 Requires a minimum of 5 concentration levels * 2009 Range Acceptable range having linearity, accuracy, precision. For Drug Substance Drug product Assay 80 to 120% of test Concentration For Content Uniformity Assay 70 to 130% of test Concentration For Dissolution Test Method +/- 20% over entire Specification Range For Impurity Assays From Reporting Level to 120% of Impurity Specification for Impurity Assays From Reporting Level to 120% of Assay Specification for Impurity/Assay Methods * 2009 Accuracy Closeness of the test results obtained by the method to the true value. * Accuracy Should be established across specified range of analytical procedure. Should be assessed using a minimum of 3 concentration levels, each in triplicate (total of 9 determinations) Should be reported as: Percent recovery of known amount added or The difference between the mean assay result and the accepted value * 2009 Accuracy Data Set (1 of 3) * Amount Added (mg) Amount Found (mg) Percent Recovery 0.0 0.0 --- 50.2 50.4 100.5 79.6 80.1 100.6 99.9 100.7 100.8 120.2 119.8 99.7 150.4 149.7 99.5 2009 Precision The closeness of agreement (degree of scatter) between a series of measurements obtained from multiple samplings of the same homogeneous sample. Should be investigated using homogeneous, authentic samples. * 2009 Precision… Considered at 3 Levels Repeatability Intermediate Precision Reproducibility * 2009 Repeatability Express the precision under the same operating conditions over a short interval of time. Also referred to as Intra-assay precision * Should be assessed using minimum of 9 determinati