分析方法验证指导原则-FDA

GuidanceforIndustryBioanalyticalMethodValidationU.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforVeterinaryMedicine(CVM)May2001BPGuidanceforIndustryBioanalyticalMethodValidationAdditionalcopiesareavailablefrom:DrugInformationBranch(HFD-210)CenterforDrugEvaluationandResearch(CDER)5600FishersLane,Rockville,MD20857(Tel)301-827-4573Internetat(HFV-12)CenterforVeterinaryMedicine(CVM)7500StandishPlace,Rockville,MD20855(Tel)301–594-1755Internetat(CDER)CenterforVeterinaryMedicine(CVM)May2001BPTableofContentsI.INTRODUCTION..................................................................................................................................................................1II.BACKGROUND....................................................................................................................................................................1A.FULLVALIDATION..............................................................................................................................................................2B.PARTIALVALIDATION........................................................................................................................................................2C.CROSS-VALIDATION...........................................................................................................................................................3III.REFERENCESTANDARD.............................................................................................................................................4IV.METHODDEVELOPMENT:CHEMICALASSAY........................................................................................................4A.SELECTIVITY.......................................................................................................................................................................4B.ACCURACY,PRECISION,ANDRECOVERY.........................................................................................................................5C.CALIBRATION/STANDARDCURVE......................................................................................................................................5D.STABILITY...........................................................................................................................................................................6E.PRINCIPLESOFBIOANALYTICALMETHODVALIDATIONANDESTABLISHMENT............................................................8F.SPECIFICRECOMMENDATIONSFORMETHODVALIDATION...........................................................................................10V.METHODDEVELOPMENT:MICROBIOLOGICALANDLIGAND-BINDINGASSAYS..................................11A.SELECTIVITYISSUES........................................................................................................................................................11B.QUANTIFICATIONISSUES.................................................................................................................................................12VI.APPLICATIONOFVALIDATEDMETHODTOROUTINEDRUGANALYSIS....................................................13ACCEPTANCECRITERIAFORTHERUN......................................................................................................................................15VII.DOCUMENTATION......................................................................................................................................................16A.SUMMARYINFORMATION.................................................................................................................................................16B.DOCUMENTATIONFORMETHODESTABLISHMENT.......................................................................................................17C.APPLICATIONTOROUTINEDRUGANALYSIS.................................................................................................................17D.OTHERINFORMATION......................................................................................................................................................19GLOSSARY....................................................................................................................................................................................20GUIDANCEFORINDUSTRY1BioanalyticalMethodValidationI.INTRODUCTIONThisguidanceprovidesassistancetosponsorsofinvestigationalnewdrugapplications(INDs),newdrugapplications(NDAs),abbreviatednewdrugapplications(ANDAs),andsupplementsindevelopingbioanalyticalmethodvalidationinformationusedinhumanclinicalpharmacology,bioavailability(BA),andbioequivalence(BE)studiesrequiringpharmacokinetic(PK)evaluation.Thisguidancealsoappliestobioanalyticalmethodsused