Analytical method validation
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This document discusses guidelines for analytical method validation. It outlines the types of analytical methods that require validation including chromatographic, spectroscopic, and dissolution methods. It describes key performance characteristics that are evaluated in validation studies such as specificity, accuracy, precision, linearity, range, detection and quantitation limits, and robustness. The document provides details on how these characteristics are tested and the acceptance criteria used to ensure the method is suitable for its intended purpose. It also discusses circumstances under which revalidation may be necessary.
![The United State Pharmacopoeia 24; The National
Formulary 19; 2000: [1225] VALIDATION OF
COMPENDIAL METHODS.
www.labcompliance.com/methods/meth_va
htm#introduction
http://www.fda.gov/cder/guidance/2396dft.htm
www.fda.gov/ohrms/dockets/
ac/02/slides/3841s1_07_lachman.PPT
http://www.fda.gov/cder/guidance/ameth.htm](https://image.slidesharecdn.com/analyticalmethodvalidation-190216100200/85/Analytical-method-validation-24-320.jpg)
Analytical method validation
- 1. Prepared By Shivanee Vyas M Pharmacy Lakshmi Narain College of Pharmacy, Indore (MP)
- 2. OBJECTIVE PUBLISHED GUIDANCES TYPES OF ANALYTICAL METHOD TO BE VALIDATED CONSIDERATIONS PRIOR TO METHOD VALIDATION TYPICAL ANALYTICAL PERFORMANCE CHARACTERISTICS USED IN METHOD VALIDATION REVALIDATION POSSIBLE QUESTIONS REFERENCES
- 3. PUBLISHED GUIDANCES ICH-Q2A “Text on Validation of Analytical Procedure: (1994) ICH-Q2B “Validation of Analytical Procedures: Methodology: (1995) CDER “Reviewer Guidance: Validation of Chromatographic Method” (1994) CDER “Submitting Samples and Analytical Data for Method Validations” (1987) CDER Draft “Analytical Procedures and Method Validation” (2000) CDER “Bioanalytical Method Validation for Human Studies” (1999) USP<1225> “Validation of Compendial Methods” (current revision)
- 4. SUBMISSION TO THE COMPENDIA RATIONALE PROPOSED ANALYTICAL PROCEDURE DATA ELEMENTS
- 5. TYPES OF ANALYTICAL PROCEDURES TO BE VALIDATED Identification tests. Quantitative tests for impurities' content. Limit tests for the control of impurities. Quantitative tests of the active moiety in samples of drug. substance or drug product or other selected components in the drug product.
- 6. CONSIDERATIONS PRIOR TO METHOD VALIDATION Suitability of Instrument Status of Qualification and Calibration Suitability of Materials Status of Reference Standards, Reagents, etc. Suitability of Analyst Status of Training and Qualification Records Suitability of Documentation Written analytical procedure and proper approved protocol with pre-established acceptance criteria.
- 7. EXAMPLES OF METHODS THAT REQUIRE VALIDATION DOCUMENTATION CHROMATOGRAPHIC METHODS SPECTROPHOTOMETRIC METHODS CAPILLARY ELECTROPHORESIS METHODS PARTICLE SIZE ANALYSIS METHODS DISSOLUTION METHODS TITRATION METHODS AUTOMATED ANALYTICAL METHODS CHROMATOGRAPHIC METHODS SPECTROPHOTOMETRIC METHODS CAPILLARY ELECTROPHORESIS METHODS PARTICLE SIZE ANALYSIS METHODS DISSOLUTION METHODS TITRATION METHODS AUTOMATED ANALYTICAL METHODS
- 8. ANALYTICAL METHOD VALIDATION Validation of an analytical method is the process by which it is established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical applications.
- 9. TYPICAL ANALYTICAL PERFORMANCE CHARACTERISTICS USED IN METHOD VALIDATION Specificity (Selectivity) Linearity Range Accuracy Precision Detection Limit Quantitation Limit Robustness System Suitability Testing
- 10. SPECIFICITY SPECIFICITY is the ability to assess unequivocally the analyte in presence of components which may be expected to be present. DETERMINATION IDENTIFICATION TESTS ASSAY AND IMPURITY TEST Impurities are available Impurities are not available
- 11. LINEARITY LINEARITY of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. DETERMINATION- Linearity should be evaluated by visual inspection of a plot of signals as a function of analyte concentration or content. .
- 13. RANGE RANGE of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. DETERMINATION-The specified range is normally derived from linearity studies and depends on the intended application of the procedure.
- 14. ACCURACY ACCURACY of an analytical method is the closeness of test results obtained by that method to the true value. DETERMINATION-Accuracy should be established across the specified range of the analytical procedure. ASSAY Drug Substance Drug Product IMPURITIES (QUANTITATION) NOTE Accuracy should be assessed using a minimum of 9 determinations over a minimum of 3 concentration levels covering the specified range (i.e., three concentrations and three replicates of each).
- 15. PRECISION PRECISION of an analytical method is the degree of agreement among individual test results when the method is applied repeatedly to multiple samplings of a homogenous sample. DETERMINATION- A sufficient number of aliquots of a homogeneous sample are assayed to be able to calculate statistically valid estimates of standard deviation or relative standard deviation. Repeatability Intermediate precision Reproducibilty
- 16. DETECTION LIMIT DETECTION LIMIT of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated, under the stated experimental conditions. DETERMINATION- Several approaches for determining the detection limit are possible, depending on whether the procedure is a non-instrumental or instrumental. BASED ON VISUAL EXAMINATION BASED ON SIGNAL TO NOISE RATIO
- 17. QUANTITATION LIMIT QUANTITATION LIMIT of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. DETERMINATION- Several approaches for determining the detection limit are possible, depending on whether the procedure is a non-instrumental or instrumental. BASED ON VISUAL EXAMINATION BASED ON SIGNAL TO NOISE RATIO
- 18. LOQ, LOD and SNR Limit of Quantitation Limit of Detection Signal to Noise Ratio noise Peak A LOD Peak B LOQ Baseline
- 19. RUGGEDNESS NOTE Included in but not in RUGGEDNESS of an analytical method is the degree of reproducibility of test results obtained by the analysis of the same samples under a variety of conditions, such as different laboratories different analyst, different instruments, different lots of reagent, different elapsed assay times, different assay temperatures, different days, etc.
- 20. ROBUSTNESS ROBUSTNESS of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. DETERMINATION- The evaluation of robustness should be considered during the development phase and depends on the type of procedure under study.
- 21. SYSTEM SUITABILITY TESTING SYSTEM SUITABILITY TESTING is an integral part of many analytical procedures. The tests are based on the concept that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral system that can be evaluated as such.
- 22. Recommended Validation Characteristics of the Various Types of Tests
- 23. REVALIDATION MAY BE NECESSARY IN THE FOLLOWING CIRCUMSTANCES: changes in the synthesis of the drug substance; changes in the composition of the finished product; changes in the analytical procedure; The degree of revalidation required depends on the nature of the changes. Certain other changes may require validation as well.
- 24. The United State Pharmacopoeia 24; The National Formulary 19; 2000: [1225] VALIDATION OF COMPENDIAL METHODS. www.labcompliance.com/methods/meth_va htm#introduction http://www.fda.gov/cder/guidance/2396dft.htm www.fda.gov/ohrms/dockets/ ac/02/slides/3841s1_07_lachman.PPT http://www.fda.gov/cder/guidance/ameth.htm