19-11-2012, 12:01 PM
Analytical considerations
Analytical considerations.ppt (Size: 990.5 KB / Downloads: 86)
Guidance
FDA Guidance for Industry
Bioanalytical method validation, May 2001
ICH Guidance for industry
Validation of analytical methods: definitions and terminology, June 1995
Validation of analytical procedures: methodology, November 1996
GCP/GLP
GCP/GLP compliance
Clinical studies have to be performed under conditions complying with the principles of Good Clinical Practice, and for analytical methods and sample data handling conditions complying with the principles of Good Laboratory Practice are required.
For older studies without statement of compliance with the above mentioned principles, the assessor should rely on the quality of the submitted report.
Discriminative
The method should be able to discriminate between the selected analyte and interfering compounds from the environment or from other compounds administered simultaneously
Precision
The analytical method should be precise enough to reveal identical results when the procedure is applied repeatedly to multiple aliquots of a single homogeneous volume of the biological matrix
Validation-specificity
Investigation of specificity should be conducted during the validation phase of the assay
The procedures used to demonstrate specificity should be clearly reported
Must be applied with structurally similar materials
Choices base on scientific judgements
Validation-LOD/LOQ
The LOD and LOQ and the method used for the LOQ should be presented
The limits should be validated by the analyses of a suitable number of samples prepared at the LOD and LOQ limits
Validation-linearity
Should be evaluated across the range of concentrations expected during the study
A minimum of five concentrations used in the range is recommended
The correlation coefficient, y-intercept slope of the regression and residual sum of squares should be submitted
Deviations from the regression line should be analysed for evaluating linearity
Validation-range
The specified range is derived from linearity studies and should cover the extremes of the concentrations probably reached during the study
The range should be justified in the report based on scientific information
Validation-accuracy
Accuracy should be assessed on samples spiked with known amounts of the analyte
Accuracy should be assessed using determinations over a minimum of 3 concentration levels (low, medium and high)
Accuracy should be reported as percent recovery from the added amount
Analysis clinical samples
The analytical method should be validated before the start of obtaining clinical samples.
Each analytical run should contain sufficient QC samples at the beginning, middle and end at at least 3 levels (LQC, MQC and HQC).