Validation and Qualification in Analytical Laboratories

314 Pages·2007·4.18 MB·English

by  Huber Ludwig

Validation and
Qualification in
Analytical
Laboratories
HUBER_978-0849382673_TP.indd 1 6/22/07 12:59:33 PM

Validation and
Qualification in
Analytical
Laboratories
Second Edition
Ludwig Huber
Agilent Technologies
Waldbronn, Germany
HUBER_978-0849382673_TP.indd 2 6/22/07 12:59:34 PM
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Huber,Ludwig,1948-
Validationandqualificationinanalyticallaboratories/LudwigHuber.–2nded.
p. ; cm.
Includesbibliographicalreferencesandindex.
ISBN-13:978-0-8493-8267-3(hardcover:alk.paper)
ISBN-10:0-8493-8267-X(hardcover:alk.paper)1.Chemistry,Analytic–Qualitycontrol.
2.Chemicallaboratories–Standards. I.Title.
[DNLM:1.Chemistry,Pharmaceutical–standards. 2.Chemistry,Analytical–standards.
3.DrugIndustry–standards. 4.Laboratories–standards. 5.QualityControl.
QV744H877v2007]
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2007020360
Preface
Validation and qualification of analytical methods and equipment are
requiredbymanyregulations,regulatoryguidancedocuments,qualitystan-
dards,andcompanypolicies.Ifexecutedcorrectly,theyalsohelptoimprove
the reliability, consistency, and accuracy of analytical data. This book,
Validation and Qualification in Analytical Laboratories, guides analysts,
laboratory managers, quality assurance managers, and validation profes-
sionals through the validation and qualification processes in analytical
laboratories.
Thevalidationandqualificationprocedurespresentedinthisbookhelp
toensurecomplianceandquality,butwithminimalextracostandadminis-
trative complexity. Its purpose is to answer the key question regarding val-
idation: How much validation is needed and how much is sufficient? The
recommendationsarecomplementaryratherthancontradictorytoanyregu-
lations,standards,orofficialguidelines.Theyarebasedmainlyoncommon
senseandcanbeusedincaseswhereinformationfromofficialguidelinesand
standardsisinsufficientforday-to-daywork.
This book addresses both international and national regulations and
qualitystandards.Itsconcept,examples,templates,andoperatingprocedures
are based on my more than twenty years of multinational experience, and
incorporateallaspectsofvalidationandqualificationinuseatthetopcom-
panies in these fields. Input has also been taken from personal discussions
with regulatory agencies, managers, and chemists at laboratories, and from
corporatequalityassurancemanagers,qualitycontrolmanagers,andvendors
ofequipmentandchemicals.Readersofthisbookwilllearnhowtospeedup
theirvalidationandqualificationprocesses,therebyavoidingtroublesome—
andcostly—reworking,andgainingconfidenceforauditsandinspections.
Readers of the best-selling first edition of this title told me that they
especiallylikedthepracticalcommon-senseapproachsupportedwithbulleted
lists, checklists, templates, and standard operating procedures with step-by-
step instructions. In this new edition, I have incorporated and further elab-
oratedonthisconcept.Forexample,Ihaveaddedtemplateswithexamples
iii
iv ValidationandQualificationinAnalyticalLaboratories
foranequipmentmasterlist,foravalidationmasterplan,andfortestingof
computersystems.Suchtoolswillhelpreaderstobetterunderstandandeasily
implementqualificationandvalidationprojects.
Asidefromupdatingthecorecontentofthefirstedition,creatingthis
revisionalsoprovidedmewiththeopportunitytoaddresstopicsthatarenew
andburgeoninginthefield.Examplesincluderiskmanagementandvalidation
offunctionalityasrequiredbytheFDA’s21CFRPart11.Riskmanagement
hasbeenrecommendedbyregulatoryagenciesandwillhelptofocusresources
onprocessesthathaveahighimpactonproductqualityanddataintegrity.If
implementedproperly,thiswillimprovethequalityofhigh-impactproducts
andreducecosts.Savingscomefromspendinglittleornotimeonprocesses
thathavealowimpactonproductquality.
In the chapter on validation of computerized systems, we have added
recommendationsforvalidationoffunctionalityasrequiredbytheFDA’sreg-
ulationforelectronicrecordsandsignatures,21CFRPart11.Thistakesinto
accountthatmoreandmorerecordsaregenerated,maintained,andarchived
oncomputersystems.
Ihavealsoaddedanewchapteronmanagingout-of-specificationtest
results and failure investigations. Proper handling of deviations from prod-
uctspecificationswithcorrectiveandpreventiveactionplansisanincreasing
concernofhealthcareagencies.Itavoidsthepossibilityofproductsentering
themarketthatareunsafeduetohighamountsofharmfulimpurities.This
chapterisalsoimportantduetothefactthatprobablymorethan30%ofall
FDAinspectionreportsshowinadequatehandlingofout-of-specificationtest
results.
This book is intended to help clarify certain current issues in the area
ofvalidationandqualificationinanalyticallaboratories.Readersareencour-
agedtosubmittheircommentsandsuggestions,especiallyiftheirexperiences
havebeendifferentindailylaboratorywork.Commentsshouldbesubmitted
totheLabComplianceWebsiteatwww.labcompliance.com.
LudwigHuber
Contents
Preface....iii
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. Regulations,Standards,andGuidelines . . . . . . . . . . . . . . . . . . . 9
3. TerminologyandValidationOverview . . . . . . . . . . . . . . . . . . . . 25
4. Risk-BasedValidationandQualification . . . . . . . . . . . . . . . . . . 37
5. MasterandProjectPlanningforEquipmentand
ComputerSystems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
6. DesignQualification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
7. InstallationQualification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
8. OperationalQualification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
9. PerformanceQualificationandMaintenance. . . . . . . . . . . . . . . . 93
10. SpecialConsiderationsforSoftwareandComputerSystems . . . . . 109
11. ValidationofAnalyticalMethods . . . . . . . . . . . . . . . . . . . . . . . 125
12. DataReviewandValidationandEvaluationofUncertainty. . . . . . 155
13. HandlingOut-of-SpecificationSituations . . . . . . . . . . . . . . . . . . 165
14. (Certified)ReferenceStandards. . . . . . . . . . . . . . . . . . . . . . . . . 179
15. People . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
16. ProficiencyTestingforExternalLaboratoryQualification . . . . . . 209
17. Audits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
AppendixA. Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
AppendixB. OQTestsforSelectedEquipment . . . . . . . . . . . . . . . 243
AppendixC. Selected(Standard)OperatingProcedures . . . . . . . . . 259
AppendixD. BooksintheAreaofQualification
andValidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
AppendixE. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Index....299
v

1
Introduction
The purpose of any chemical analytical measurement is to get consistent,
reliable, and accurate data. There is no doubt that incorrect measurement
resultscanleadtotremendouscosts,forexample:
(cid:1) Ifaproductwithincorrectlymeasuredspecificationsismarketed,it
mayhavetoberecalled.
(cid:1) Ifdrugswithundetectedimpuritiesaredistributed,theycanhavea
negativeimpactonpeoples’health.
(cid:1) If harmful contaminants in environmental or food samples are not
detected,theycanbedangeroustotheenvironmentortoconsumers.
Inaddition,reportingincorrectanalyticalresultsatanyparticulartime
leadstolossofalaboratory’sconfidenceinthevalidityoffutureresults.There-
fore,anylaboratoryshoulddoitsutmosttoensuremeasuringandreporting
reliableandaccuratedatawithinaknownlevelofconfidence.Validationand
qualificationofprocessesandequipmentwillhelptomeetthisgoal.
Thereisasecondaspecttotheimportanceofvalidationandqualifica-
tion,whichisequallyimportantforthoseworkinginaregulatedoraccred-
ited environment. Even though validation and qualification are frequently
not directly spelled out in regulations and official guidelines, such as Good
LaboratoryPractice(GLP)andGoodManufacturingPractice(GMP),orin
accreditationstandards,suchastheInternationalOrganizationforStandard-
ization(ISO)standard17025,theyareusuallyrequired.Thisisconfirmedby
typical statements such as this one that appears in the U.S. cGMP (current
GoodManufacturingPractice)regulations(1):“Equipmentshallberoutinely
calibrated,inspectedandcheckedaccordingtoawrittenprogramtoensure
properperformance.”Becauseoftheirdirectimpactonproductqualityand
consumersafety,analyticaltestresultsinpharmaceuticalqualitycontrolare
consideredhigh-riskrecordsandarefrequentlytargetsofinspectionsbythe
1