国际上不同分析方法验证准则概述

Mintacm szerkesztse,Mintaszveg szerkesztse,Msodik szint,Harmadik szint,Negyedik szint,tdik szint,2009,*,Mintacm szerkesztse,Mintaszveg szerkesztse,Msodik szint,Harmadik szint,Negyedik szint,tdik szint,2009,*,Mintacm szerkesztse,Mintaszveg szerkesztse,Msodik szint,Harmadik szint,Negyedik szint,tdik szint,2009,*,国际上不同分析方法验证的准则概述,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,7/8/2010,2,Slide,3,Criteria for Method Validation,Limit of detection,Limit of quantitation,Precision (Intermediate precision),Accuracy,Linearity/Range,Selectivity/Specificity,Ruggedness,Robustness,Actual validation effort depends on the analysis problem,Proof suitability for intended use,3,Definition Method Scope,Define Validation Criteria,Test,Define Routine Tests,Validation of Analytical Methods,Sample matrix,Compounds,Equipment, Location,Optimize method parameters,Define performance characteristics,Acceptance criteria,Develop test cases,Preliminary tests,Final tests,SOPs,System Suitability tests,Analytical quality control,Validation Plan,Validation Report,4,Slide,5,Scope of the Method,Compounds, Sample matrix,Qualitative/quantitative information,Operating range,(concentration),Performance characteristics,Instrument,(specific brand, product e.g., Agilent 1200 Series),Location,(specific lab, specific site, global),Specific regulatory/standards requirements,(e.g., part 21 CFR Part 11, ISO17025),5,International regulatory bodies and their guidelines on different aspects of MV,Body,Full name,Guidance on,Eurachem,Focus for Analytical Chemistry in Europe,Method validation,CITAC,Cooperation of International Traceability in Analytical Chemistry,Proficiency testing,Quality Assurance,EA,European Cooperation for Accreditation,Accreditation,CEN,European Committee for Normalization,Standardization,IUPAC,International Union of Pure & Applied Chem.,Method validation,ISO,International Standardization Organisation,Standardisation,AOAC,ILAC,Association of Official Analytical Chemists,International Laboratory Accreditation Cooperat.,Internal qual. Control,Proficiency testing,Accreditation,FDA,US Food and Drug Administration,Method validation,USP,United States Pharmacopoeia,Method validation,ICH,International Conference on Harmonization,Method validation,6,Examples of Methods That Require Validation Documentation,Chromatographic Methods - HPLC, GC, TLC, GC/MS, etc.,Pharmaceutical Analysis - In support of CMC.,Bioanalytical Analysis - In support of PK/PD/Clinical Studies.,Spectrophotometric Methods,UV/VIS, IR, NIR, AA, NMR, XRD,MS,Capillary Electrophoresis Methods - Zone, Isoelectric Focusing,Particle Size Analysis Methods - Laser, Microscopic, Sieving, SEC, etc.,Automated Analytical Methods - Robots, Automated Analysis.,7/8/2010,7,Considerations Prior to Method Validation,Suitability of Instrument,Status of Qualification and Calibration,Suitability of Materials,Status of Reference Standards, Reagents, Placebo Lots,Suitability of Analyst,Status of Training and Qualification Records,Suitability of Documentation,Written analytical procedure and proper approved protocol with pre-established acceptance criteria,7/8/2010,8,Validation 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 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.,7/8/2010,9,Purpose of Method Validation,Identification of Sources and Quantitation of Potential errors,Determination if Method is Acceptable for Intended Use,Establish Proof that a Method Can be Used for Decision Making,Satisfy,R,egulatory Requirements,10,V,alidation,R,eport,type of compounds and matrix,detailed chemicals, reagents, reference standards and control,sample preparations,procedures for quality checks of standards and chemicals used,safety considerations,method parameters,critical parameters indicated from robustness testing,listing of equipment and its functional and performance,requirements, e.g. cell dimensions, baseline noise, column,temperature range,detailed conditions on how the experiments were conducted,including sample preparation,statistical procedures and representative calculations,procedures for quality control in the routine (e.g., system,suitability tests),representative plots, e.g. chromatograms, spectra and calibration,curves,method acceptance limit performance data,the expected uncertainty of measurement results,criteria for revalidation,person who developed and initially validated the method,summary and conclusions,11,US,FDA,Validation Guidelines,FDA,Guidance for Industry,:,Analytical Procedures and,Methods 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,(,Draft,),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 2007,12,US,FDA,Validation Guidelines,FDA,Guidance for Industry,:,Analytical Procedures and,Methods 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,(,Draft,),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 2007,13,ICH,Validation Guidelines,ICH - Guidance for Industry: Q2A - Text on Validation of Analytical Procedures,ICH - Guidance for Industry: Q2B - Validation of Analytical Procedures - Methodology,14,EU,Validation Guidelines,EURACHEM The Fitness for Purpose of Analytical Methods Probably the most detailed official document for method validation, 1998,EMEA Guide Residues: Guidance for generating and reporting methods of analysis in support of pre-registration data requirements for Annex II (part A, Section 4) and Annex III (part A, Section 5) of Directive 91/414, Nov. 2000,15,Australian,Validation Guidelines,TGA Guide (Australia)-Starting Material Analytical Procedure Validation for Complimentary Medicines,March 2006,NATA Technical Note #17 - Guidelines for the Validation and Verification of Chemical Test Methods, April 2009,16,US EPA,Validation Guidelines,US 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. 31,2003,40 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 Act (RCRA) Program, Washington, 1995,17,Validation Guidelines,IUPAC Technical Report: Harmonized Guidelines for Single Laboratory Validation of Methods of Analysis Pure Appl. Chem., Vol. 74, No. 5, pp. 835- 855, 2002,AOAC How to Meet ISO 17025 Requirements for Method Verification. Prepared by AOAC INTERNATIONAL 481 N. Frederick Ave, Suite 500, 2007,United States Pharmacopeia, Validation of Compendial Methods, e.g., XXVI, Rockville, MD, 2002 2149/2152 (Chapter 1225) ,1999,18,Regulatory and Compliance Requirements Review,FDA 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 FDA, other agencies and industry task forces have developed guidelines for method validation.,19,Validation Requirements & Parameters,20,ICH/USP Validation Requirements & Parameters,Specificity,Linearity,Range,Accuracy,Precision,Repeatability,Intermediate Precision,Reproducibility,Limit of Detection,Limit of Quantitation,ICH,Specificity,Linearity and Range,Accuracy,Precision,Limit of Detection,Limit of Quantitation,Ruggedness,Robustness,USP,21,USP Categories,Category 1: Quantitation of major components or,active ingredients,Category 2: Determination of impurities or,degradation products,Category 3: Determination of performance,characteristics,22,USP Data Elements Required For Assay Validation,Analytical,Performance,Parameter,Assay Category 1,Assay Category 2,Assay Category 3,Quantitative,Limit Tests,Accuracy,Yes,Yes,*,*,Precision,Yes,Yes,No,Yes,Specificity,Yes,Yes,Yes,*,LOD,No,No,Yes,*,LOQ,No,Yes,No,*,Linearity,Yes,Yes,No,*,Range,Yes,Yes,*,*,Ruggedness,Yes,Yes,Yes,Yes,* May be required, depending on the nature of the specific test.,23,ICH Validation Characteristics vs. Type of Analytical Procedure,24,AOAC,Categories,of Chemical Methods,Category 1:,Confirmation of Identity,Category 2:,Quantifying an analyte at a low concentration,Category 3:,Determining if an analyte is present above or below a specified, low concentration (often called a Limit,Test). The specified concentration is close to the LOQ.,Category,4,:,Quantifying an analyte at a high concentration,Category,5,:,Determining if an analyte is present above or below a specified, high concentration (often called a Limit,Test). The specified concentration is substantially above the,L,OQ.,Category,6,:,Qualitative test.,25,AOAC,Validation Characteristics vs. Type of Analytical Procedure,Type of Analytical,Procedure,Performance Characteristics Included in a Validation,Category 1,Category,2,Category,3,Category,4,Category,5,Category,6,Accuracy,No,Yes,No,Yes,Yes,No,Precision,No,Yes,No,Yes,Yes,No,Specificity,Yes,Yes,Yes,Yes,Yes,Yes,LOD,No,Yes,Yes,Yes,/,No,No,No,LOQ,No,Yes,No,Yes,/,No,No,No,Ruggedness,No,Yes,No,Yes,No,No,Linearity/Range,No,Yes,No,Yes,No,No,26,AOAC,Validation Characteristics,-,Analyte concentration versus precision within orbetween days,27,AOAC,Validation Characteristics,-,Analyte recovery at different concentrations,28,How do we Know the expectations of the FDA?,FDA Form 483,FDA Warning Letters,Personal Experiences,29,483 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, thermal degradation and photolysis,degradation schematic,for the active ingredient that identifies the major degradation products,was not included for each product.,FDA Waning Letter,On addition to the example of modifying both compendial methods and customer supplied methods, we also observed the use of,unvalidated in-house methods,as well as,unvalidated modifications,to in-house methods.,A statement indicating that the method has not been validated in the particular formulation was included in the certificate of analysis for,use of this statement does not absolve,from using valid, accurate, and,reproducible methods. (June 2000),FDA Systems Based Inspection:Laboratory System,Method,Validation,13%,Training/Qual.,4%,Stability Program,21%,Inadequate,Records,27%,Controls. General,35%,Feb,July 2002: 212 Inspections (US),* Reference: Albinus D,Sa, FDA, CDER Office of Compliance, from AAPS, Nov. 2002 presentation.,Related Site,33,