EMA-Guideline+on+bioanalytical+method+validation(1

7WestferryCircus●CanaryWharf●LondonE144HB●UnitedKingdomTelephone+44(0)2074188400Facsimile+44(0)[e-mail]©EuropeanMedicinesAgency,2011.Reproductionisauthorisedprovidedthesourceisacknowledged.21July2011EMEA/CHMP/EWP/192217/2009CommitteeforMedicinalProductsforHumanUse(CHMP)GuidelineonbioanalyticalmethodvalidationDraftagreedbytheEfficacyWorkingPartySeptember2009AdoptionbyCHMPforreleaseforconsultation19November2009Endofconsultation(deadlineforcomments)31May2010AgreedbyPharmacokineticsWorkingParty(PKWP)June2011AdoptionbyCHMP21July2011Dateforcomingintoeffect1February2012Commentsshouldbeprovidedusingth[e-mail],EMEA,Guideline,validation,bioanalyticalmethod,analysesGuidelineonbioanalyticalmethodvalidationTableofcontents1.Introduction(background)......................................................................32.Scope.......................................................................................................33.Legalbasis..............................................................................................34.Methodvalidation....................................................................................44.1.Fullvalidationofananalyticalmethod...................................................................44.1.1.Selectivity................................................................................................54.1.2.Carry-over...............................................................................................54.1.3.Lowerlimitofquantification........................................................................64.1.4.Calibrationcurve.......................................................................................64.1.5.Accuracy..................................................................................................74.1.6.Precision..................................................................................................74.1.7.Dilutionintegrity.......................................................................................84.1.8.Matrixeffect.............................................................................................84.1.9.Stability...................................................................................................94.2.Partialvalidation..............................................................................................104.3.Crossvalidation...............................................................................................105.Analysisofstudysamples.....................................................................105.1.Analyticalrun..................................................................................................115.2.Acceptancecriteriaofananalyticalrun...............................................................115.3.Calibrationrange.............................................................................................125.4.Reanalysisofstudysamples..............................................................................125.5.Integration......................................................................................................136.Incurredsamplesreanalysis..................................................................137.Ligandbindingassays...........................................................................147.1.1.Fullvalidation.........................................................................................147.2.Partialvalidationandcross-validation.................................................................177.3.Analysisofstudysamples..................................................................................177.3.1.Analyticalrun.........................................................................................177.3.2..Acceptancecriteriaforstudysampleanalysis.............................................177.3.3.Incurredsamplesreanalysis......................................................................188.Reports..................................................................................................188.1.Validationreport..............................................................................................188.2.Analyticalreport..............................................................................................19Definitions.................................................................................................20Page2/22ExecutivesummaryThisguidelinedefineskeyelementsnecessaryforthevalidationofbioanalyticalmethods.Theguidelinefocusesonthevalidationofthebioanalyticalmethodsgeneratingquantitativeconcentrationdatausedforpharmacokineticandtoxicokineticparameterdeterminations.Guidanceandcriteriaaregivenontheapplicationofthesevalidatedmethodsintheroutineanalysisofstudysamplesfromanimalandhumanstudies.1.Introduction(background)Measurem