国际上不同分析方法验证准则概述课件

1、国际上不同分析方法验证的准则概述7/8/2010蔡磊明分析方法验证是论证某一分析方法适用于其用途的过程。 Analytical method validation is the process to confirm that the analytical procedure employed for a specific test is suitable for its intended use. 分析方法验证Method Validation 7/8/2010Slide 3Criteria for Method ValidationLimit of detectionLimit of qua

2、ntitation Precision (Intermediate precision)Accuracy Linearity/RangeSelectivity/SpecificityRuggednessRobustnessActual validation effort depends on the analysis problemProof suitability for intended useDefinition Method ScopeDefine Validation CriteriaTestDefine Routine TestsValidation of Analytical M

3、ethodsSample matrixCompoundsEquipment, LocationOptimize method parametersDefine performance characteristicsAcceptance criteriaDevelop test casesPreliminary testsFinal testsSOPsSystem Suitability testsAnalytical quality controlValidation PlanValidation ReportInternational regulatory bodies and their

4、guidelines on different aspects of MVBodyFull nameGuidance onEurachemFocus for Analytical Chemistry in EuropeMethod validationCITACCooperation of International Traceability in Analytical ChemistryProficiency testingQuality AssuranceEAEuropean Cooperation for AccreditationAccreditationCENEuropean Com

5、mittee for NormalizationStandardizationIUPACInternational Union of Pure & Applied Chem. Method validationISOInternational Standardization OrganisationStandardisationAOACILACAssociation of Official Analytical ChemistsInternational Laboratory Accreditation Cooperat.Internal qual. ControlProficiency te

6、stingAccreditation FDAUS Food and Drug AdministrationMethod validationUSPUnited States PharmacopoeiaMethod validationICHInternational Conference on HarmonizationMethod validationExamples of Methods That Require Validation DocumentationChromatographic Methods - HPLC, GC, TLC, GC/MS, etc. Pharmaceutic

7、al Analysis - In support of CMC. Bioanalytical Analysis - In support of PK/PD/Clinical Studies. Spectrophotometric Methods UV/VIS, IR, NIR, AA, NMR, XRD,MSCapillary Electrophoresis Methods - Zone, Isoelectric Focusing Particle Size Analysis Methods - Laser, Microscopic, Sieving, SEC, etc. Automated

8、Analytical Methods - Robots, Automated Analysis.77/8/2010Validation Step Define the application, purpose and scope of the method. Analytes? Concentration? Sample matrices? Develop a analytical method. Develop a validation protocol. Qualification of instrument. Qualify/train operator Qualification of

9、 material. Perform pre-validation experiments. Adjust method parameters and/or acceptance criteria if necessary. Perform full validation experiments. Develop SOP for executing the method in routine analysis. Document validation experiments and results in the validation report.97/8/2010Purpose of Met

10、hod ValidationIdentification of Sources and Quantitation of Potential errorsDetermination if Method is Acceptable for Intended UseEstablish Proof that a Method Can be Used for Decision MakingSatisfy Regulatory RequirementsValidation Reporttype of compounds and matrixdetailed chemicals, reagents, ref

11、erence standards and control sample preparationsprocedures for quality checks of standards and chemicals usedsafety considerationsmethod parameterscritical parameters indicated from robustness testinglisting of equipment and its functional and performance requirements, e.g. cell dimensions, baseline

12、 noise, column temperature rangedetailed conditions on how the experiments were conducted, including sample preparationstatistical procedures and representative calculationsprocedures for quality control in the routine (e.g., system suitability tests)representative plots, e.g. chromatograms, spectra

13、 and calibration curvesmethod acceptance limit performance datathe expected uncertainty of measurement resultscriteria for revalidationperson who developed and initially validated the methodsummary and conclusionsUS FDA Validation GuidelinesFDA Guidance for Industry: Analytical Procedures and Method

14、s Validation (DRAFT), August 2000 FDA Policy guide: Requesting Methods Validation for Abbreviated New Drug Applications (ANDAs), May 1998 FDA Guidance for Industry: Bioanalytical Method Validation, May 2001 FDA Guidance: Mass, Spectrometry for Confirmation of the Identity of Animal Drug Residues (Dr

15、aft), FDA Guidance: Guideline for Submitting Samples and Analytical Data for Methods Validation FDA Guidance: Protocol for the Conduct of Method Transfer for Type C Medicated Feed Assay Methods, May 2007US FDA Validation GuidelinesFDA Guidance for Industry: Analytical Procedures and Methods Validati

16、on (DRAFT), August 2000 FDA Policy guide: Requesting Methods Validation for Abbreviated New Drug Applications (ANDAs), May 1998 FDA Guidance for Industry: Bioanalytical Method Validation, May 2001 FDA Guidance: Mass, Spectrometry for Confirmation of the Identity of Animal Drug Residues (Draft), FDA

17、Guidance: Guideline for Submitting Samples and Analytical Data for Methods Validation FDA Guidance: Protocol for the Conduct of Method Transfer for Type C Medicated Feed Assay Methods, May 2007ICH Validation GuidelinesICH - Guidance for Industry: Q2A - Text on Validation of Analytical Procedures ICH

18、 - Guidance for Industry: Q2B - Validation of Analytical Procedures - MethodologyAustralian Validation GuidelinesTGA Guide (Australia)-Starting Material Analytical Procedure Validation for Complimentary Medicines,March 2006NATA Technical Note #17 - Guidelines for the Validation and Verification of C

19、hemical Test Methods, April 2009US EPA Validation GuidelinesUS EPA Guide to Method Flexibility and Approval of EPA Water Methods 40 CFR Part 136 Guidelines Establishing Test Procedures for the Analysis of Pollutants; Analytical Methods for Biological Pollutants in Ambient Water; Final Rule, Jan. 31,

20、200340 CFR Parts 136 and 503 Guidelines Establishing Test Procedures for the Analysis of Pollutants; Analytical Methods for Biological Pollutants in Wastewater and Sewage Sludge:March 26, 2007 US EPA, Guidance for methods development and methods validation for the Resource Conservation and Recovery

21、Act (RCRA) Program, Washington, 1995Regulatory and Compliance Requirements ReviewFDA regulations such as GMP, GLP and GCP and quality standards such as ISO17025 require analytical methods to be validated before and during routine use. There are no specific regulations on method validations but the F

22、DA, other agencies and industry task forces have developed guidelines for method validation. Validation Requirements & Parameters ICH/USP Validation Requirements & Parameters SpecificityLinearityRangeAccuracyPrecision RepeatabilityIntermediate PrecisionReproducibilityLimit of DetectionLimit of Quant

23、itationICHSpecificityLinearity and RangeAccuracyPrecision Limit of DetectionLimit of QuantitationRuggednessRobustnessUSPUSP CategoriesCategory 1: Quantitation of major components or active ingredientsCategory 2: Determination of impurities or degradation productsCategory 3: Determination of performa

24、nce characteristicsUSP Data Elements Required For Assay ValidationAnalytical PerformanceParameterAssay Category 1Assay Category 2Assay Category 3QuantitativeLimit TestsAccuracyYesYes*PrecisionYesYesNoYesSpecificityYesYesYes*LODNoNoYes*LOQNoYesNo*LinearityYesYesNo*RangeYesYes*RuggednessYesYesYesYes*

25、May be required, depending on the nature of the specific test.ICH Validation Characteristics vs. Type of Analytical ProcedureType of Analytical ProcedureIdentificationImpurity testingAssayQuantitativeLimit TestsAccuracyNoYesNoYesPrecision RepeatabilityNoYesNoYes Interm. Prec.NoYesNoYesSpecificityYes

26、YesYesYesLODNoNoYesNoLOQNoYesNoNoLinearityNoYesNoYesRangeNoYesNoYesAOAC Validation Characteristics vs. Type of Analytical ProcedureType of Analytical ProcedurePerformance Characteristics Included in a ValidationCategory 1Category 2Category 3Category 4Category 5Category 6AccuracyNoYesNoYesYesNoPrecis

27、ionNoYesNoYesYesNoSpecificityYesYesYesYesYesYesLODNoYesYesYes/NoNoNoLOQNoYesNoYes/NoNoNoRuggednessNoYesNoYesNoNoLinearity/RangeNoYesNoYesNoNoAOAC Validation Characteristics - Analyte concentration versus precision within orbetween daysHow do we Know the expectations of the FDA?FDA Form 483FDA Warnin

28、g LettersPersonal Experiences483 Observations There was inadequate method validation specificity data to demonstrate that each method was capable of distinguishing the active ingredient from its impurities and degradation products.Specificity studies did not include the minimum stress conditions of acid and base hydrolysis, oxidation, the