PeterBoogaard

IndustrialLabAutomation
Consultancy&Training
www.IndustrialLabAutomation.com
peterboogaard@industriallabautomation.com
+31(654)263516(cell)
+31(182)379103(land)
industriallabautomation
QbD&PAT
TheScientistIsNoLongerInTheLaboratory,
ButIntegratedInTheOverallQualityProcess
1
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
TheScientistIsNoLongerInTheLaboratory,
butIntegratedInTheOverallQualityProcess
2
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
StopthinkingTechnology &products
QbD&PAT TheScientistIsNoLongerInThe
Laboratory,ButIntegratedInTheOverallQuality
Process
3
QbD&PAT TheScientistIsNoLongerIn
TheLaboratory,ButIntegratedInThe
OverallQualityProcess
4
TheQbDpromise
Adoption,Successes,andChallenges June2010status
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
5
6
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
Ifyoucantdescribe
whatyouredoingas
aprocess,youdont
knowwhatyouare
doing.
W.EdwardDeming
7
QbD&PAT TheScientistIsNoLongerInThe
Laboratory,ButIntegratedInTheOverallQuality
Process
QualitybyDesign(QbD)
Who?
JosephM.Juran(19042008) oneoftwointernationallyacclaimedquality
guru'softhe20thCentury
BuiltontheworkofEdwardsDeming
When?
Firstdevelopedandpublishedin1985
BasedonJuransexperiencewithJapanesemanufacturingorganizationswhere
thedriveforqualityisverystrong
What?
Itconsidersallthefactorsthatinfluenceproductquality
Itseekstoensureproductqualityisconsideredfromtheearlieststagesof
development
Itprovidestoolstohelpensurethatcomponentqualitydeliversproductquality
Qualityisplannedintotheproduct ordesignedintotheproduct
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
8
HowJurandescribedQbD
Thinking
About
Quality
Planning
Strategic
Quality
Planning
Multi
Functional
Quality
Planning
Departmental
Quality
Planning
Establish
Quality
Goals
Planninghow
wecanensure
thatwedeliver
thehighest
qualityproduct
consistently
Provide
Measurement
Develop
Process
Features
Develop
Process
Controls
Developing
systematic
manufacturing
processesthat
deliverproduct
whichisrightfirst
time,everytime
Determine
Customer
Needs
Identify
Customers
Develop
Product
Features
Understanding
whatour
customerwants,
andhowwecan
deliverit
HowthePharma
implementation
ofQbD
compareswith
Juransapproach
today.
PHARMA
Quality
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
9
Courtesy:GawayneM.Jones PhilipMorrisInternational
Poll QbDisheretostay?
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
10
EvolutionoftheGuidelines
SourceISPE
ICHQ8
(R2)
21CFR
P11
GAM
v5
RiskM
GAMP
v4
(GxP)
ICHQ11toapplyforchemicalandbiotechnological&Biologicalentities(smallandlargemolecules).Workinprogress.Concept
paperwasapprovedbytheICHsteeringcommitteein2008.InitialreleaseupdateinMunichNovember2011.May1
st
2012,
GuidelineisrecommendedforadoptiontothethreeregulatorypartiestoICH
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
11
Product
Quality
Life
Cycle
PQLI
RelevantAgencies&Societies
ISPE,theInternationalSocietyforPharmaceuticalEngineering,isthe
world'slargestnotforprofitassociationdedicatedtoeducatingand
advancingpharmaceuticalmanufacturingprofessionalsandtheirindustry.
TheInternationalConferenceonHarmonization.ICHisajointinitiative
involvingbothregulatorsandresearchbasedindustryrepresentativesof
theEuropeanUnion,JapanandtheUSAinscientificandtechnical
discussionsofthetestingproceduresrequiredtoassessandensurethe
safety,qualityandefficacyofmedicines.
TheUSFoodandDrugAdministration(FDA)isresponsibleforprotecting
thepublichealthbyassuringthesafety,efficacy,andsecurityofhuman
andveterinarydrugs,biologicalproducts,medicaldevices,foodsupply,
cosmetics,andproductsthatemitradiation.
AmericanSocietyforTestingandMaterials
TheInternationalSocietyofAutomationisaleading,global,nonprofit
organizationthatissettingthestandardforautomation
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
12
ICHGuidelinesOverview
Background
ICHQ8(R2)PharmaceuticalDevelopment
Providesinformationonhowtopresentknowledgegainedwhenapplying
scientificapproachesandqualityriskmanagementfordevelopingand
manufacturingaproduct.
ICHQ9QualityRiskManagement
Providesinformationregardingsystematicapproachestoqualityrisk
management.
ICHQ10PharmaceuticalQualitySystem
EstablishesanewICHtripartitemodelforaneffectivequalitymanagement
systemforthepharmaceuticalindustry.Themodelisreferredtoasthe
pharmaceuticalqualitysystem(PQS).
ICHQ11toapplyforsmallandlargemolecules.Workinprogress
ConceptpaperwasapprovedbytheICHsteeringcommitteein2008.Initial
releaseupdateinMunichNovember2011
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
13
KnowledgeManagement
ICHQ10PharmaceuticalQualitySystemmodel
Technology
Transfer
Commercial
Manufacturing
Discontinuation
P
r
i
o
r

K
n
o
w
l
e
d
g
e
ManagementResponsibilities
ProcessPerformance&productQualityMonitoringSystem
PreventiveAction/CorrectiveAction(PACA/CAPA)system
ChangeManagementSystem
ManagementReview
QualityRiskManagement
GMP
4PQS
elements
Enablers
Pharmaceutical
Development
Research
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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ICHQ10 Scope
ICHQ10isamodel forapharmaceuticalqualitysystemthat
canbeimplementedthroughoutthedifferentstagesofa
productlifecycle.
ICHQ10describesonecomprehensivemodelforaneffective
pharmaceuticalqualitysystemthatisbasedonISO standard
qualityconcepts,includesapplicableGMPregulations,and
complementsICHQ8PharmaceuticalDevelopmentand
ICHQ9QualityRiskManagement.
MuchofthecontentofICHQ10applicabletomanufacturing
sitesiscurrentlyspecifiedbyregionalGMPrequirements.
ICHQ10isnotintendedtocreateanynewexpectations
beyondcurrentregulatoryrequirements.
15
Source:ICHQ10guideline
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
AnillustrationofaDesignSpace
Themultidimensional combinationand
interactionofinputvariables(e.g.
materialattributes)andprocess
parametersthathavebeen
demonstratedtoprovideassuranceof
quality.
Workingwithinthedesignspaceisnot
consideredasachange.
Movementoutofthedesignspaceis
consideredtobeachangeandwould
normallyinitiatearegulatorypost
approvalchangeprocess.
Designspaceisproposedbythe
applicantandissubjecttoregulatory
assessmentandapproval.
16
CourtesyGSK
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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AnillustrationofRiskbasedprocedure
KnowledgeDesignControlSpace
CourtesyIDBS
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
QbD,aniterativeprocess,enabledbyknowledge
ICHQ8,Q9,&Q10
Developmentofacontrol
strategyforaproductisan
iterativeactivityas
knowledgeaboutthe
productandmanufacturing
processevolves
Knowledgeisalsoshared
betweendevelopmentand
supplyovertheproduct
lifecycletoenable
continualimprovement
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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TargetproductProfile
CQAs
RiskAssessment
DesignSpace
ControlStrategy
LifeCyclemanagement
Howdotheycompare?
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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Source:ISPE
KnowledgeManagement
ICHQ10PharmaceuticalQualitySystemmodel
Technology
Transfer
Commercial
Manufacturing
Discontinuation
P
r
i
o
r

K
n
o
w
l
e
d
g
e
ManagementResponsibilities
ProcessPerformance&productQualityMonitoringSystem
PreventiveAction/CorrectiveAction(PACA/CAPA)system
ChangeManagementSystem
ManagementReview
QualityRiskManagement
GMP
4PQS
elements
Enablers
Pharmaceutical
Development
Research
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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1.ProcessPerformanceand
ProductQualityMonitoringSystem
4PQS
elements
2.CAPAbecomesPACA
Data&ContextisKing
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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Pharma
IndustryToday
Deviations
Rejects
Datagaps
Reactive
ThePromiseof
Q10/QbD
Few
surprises
Datadriven
Competitive
advantage
Predictive
4PQS
elements
3.ChangeManagementModel
Propose
AgreetoDevelop
Evaluate
ApprovaltoImplement
Stopifproposalisrejected
Implement
ImplementandExecute
Review
EvaluateEffectivenessof
Change
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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4PQS
elements
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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4.ManagementreviewstoimproveQuality
Management Review of Process Performance and Product Quality throughout the Product Lifecycle
Q10providesignificantbetterguidance
Clearcommunication andescalation process
Productcomplaints
Identifyingearlywarningsignalsofproductqualityissuesinthefield
ProductAssessment&Trending
Proactiveassessmentofproductqualityattributesacrossthemanufacturing
process
ProductQualityStewards
SinglepointofContactforQualitytokeystakeholders
Formalcommunicationandescalationprocess?
Whoneedstobeinformed?
Whentobeinformed?
Howmusttheybeinformed?
QAperformanceindicatorsnottobeusedasblametool
Reviewmustbesystematic partoftheroutine
4PQS
elements
ProcessAnalyticalTechniques(PAT)
Introduction
Industrycases
HotMeltExtrusionProcess(NIR)
InsulinIPMReleaseProcess(UPLC)
JUNAVIARTRTControlStrategy(NIR)
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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WhyPAT?
Increaseprocessunderstanding
Reducedevelopmentandscaleuptime
Reduceproductioncycletimes
Enableuseofalternative(lessexpensive)rawmaterials
Reducewastageduringproduction
Preventrejectionofbatches
improvementinqualityandconsistencyofquality
Enablerealtimereleaseofproduct
Improveenergyandmaterialuse
Facilitatecontinuousprocessing
Releasethecapabilityofautomationtoimprovethe
productionprocess
Source:pharmmanufacturing
26
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
Poll ThefutureofPATrelieson
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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QbD&PATConcepts
QualityCulture
ObstaclesQbD
Rootcause
PAT
Lifecycle
Preventivevs.Proactive
ManagementResponsibility
BusinessCaseforPharmaceuticalQuality
Processperformance/processcapability
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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ProcessAnalyticalTechniques(PAT)
Whereapplying?
Indevelopment:
PATwillleadtomoreprocessknowledge.More
knowledgeresultsinbetterunderstanding,less
productvariations,higherqualityprediction,more
robustprocessesandbecausewehavemore
knowledge,identifyingproductswhowillnotmake
finalinvestigationwillbeearlierinthelifecycle.
Majorsavings.
Inproduction:
PATwillleadtofasterreleaseofbatches,because
nooffline(laboratory)testingwillbeneeded.QbD
scientificriskbasedapproachwillresultinless
testing,becausewegainmoreknowledgeinthe
differentmanufacturingstages.Batchreleasecan
changefromdaystohours.
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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Courtesy:G.K.Raju,MITPHARMI,
AdvantagesQbD&PAT
Workingwithinthedesignspaceisnot
generallyconsideredasachangeofthe
approvedrangesforprocessparametersand
productattributes.
Deemphasizesendproducttestingandmay
eliminatecertainreleasetests.(RTRT)
Diminishtheburdenforvalidating systems
Designspaceconceptcanapplytocurrently
approvedproducts
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
30
ManyToolsinthePATToolbox
Probes(Temp,pH)
DissolvedGas(0
2
,CO
2
)
Headspace/Environmental(MassSpec)
TotalOrganicCarbon(TOC)
NearInfrared(NIR)
Infrared(IR)
Raman
UVvisible
GasChromatography(GC)
FourierTransformInfrared(FTIR)
XRayPowderDiffraction(XRPD)
TerahertzPulseSpectroscopy(TPS)
AcousticResonanceSpectrometry(ARS)
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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ExamplesofwhatPATcanmeasure.
APIprocessstependpoints
ResidualSolventlevels
ParticleSize
Identity
GranulationProgressandCompletion
DryingEndpoint
ContentUniformity
BlendUniformity
Assay
Weight
Hardness
Thickness
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
32
ExampleHotMeltExtrusion
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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Existingsituation OralSoliddosage
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
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PATBasics HolisticApproach.
NIRspectrometer
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
35
36
Example:JANUVIARTRT
ControlStrategy
APIBlend
LubricantBlend
Compress
Filmcoat
PAT Testing
Approach
Manufacturing Floor
Disintegration
NIR ID
Appearance
Manufacturing Floor
NIR Composite Assay
On-line Dosage Uniformity by
Weight
Traditional Release
Approach
Laboratory
Lab Tests
HPLC
Content Uniformity
Composite Assay
Degradates
ID
Dissolution
Appearance
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
PATROLUPLCenablesLCtoberealtime
Disruptivetechnology,notadisruptivetechnique
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
37
3350
Analytical
Reports
(Dec08 Mar09)
BeforeImplementation AfterImplementation
67 folders 4folders
Thewaytomoresuccessispaperless?
38
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
Theprincipleofapaperlessprocesswill
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
39
Eng
Maint
HIST LIMS ERP
CAPA
MES
Paper Records
Raw
Materials
Process
Step 1
Process
Step 2
Process
Step 3
Process
Steps
Final
Product
Courtesy
AegisCorp
40
InvestigationofaPharmaProcess
Connectingtheinformationsilos
Explicitvs.Tacit
contextisKing
R
a
n
k
i
n
g
K
n
o
w
l
e
d
g
e

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c
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W
h
e
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e

i
t

i
s
I
m
p
a
c
t
1 Tacit Scientists
Explicit ELN
2 Discovery CRO Projectteam Explicit SecuredELN
3 Summaryoflabdevelopment Ananlytical Registrationteam Explicit Localteamworkspace
4 Performanceofsimilarproduct Development Scaleupteam Tacit Localsites
5 TechTransfer Development Manufacturing Explicit Manufacturingdatabases
6 CAPA Development Quality Explicit CAPAdatabase
7 Backup IT Organisation Explicit ITInfrastructure
8 Security IT&Quality Legal Explicit SecuredELN
9
Discovery R&D Scientists
41
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
42
WheretostartinthemovetowardsaPaperlesslaboratory?
43
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
Whatsinitformesyndrome
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Regulatorysupport
CustomerComplaint
Financialimpact
IPProtection
IT
Easeofupgrade
ProcessUnderstanding
(QbD)
R&DCollaboration
IntegratedProcesses
ROI/TCO
Development
Management
Manufacturing
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
44
PaperlessLabProcess
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
45
Howdowespendourtime?
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
46
NonprocessorientedworkinaQAorganization
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
18.0%
20.0%
Search Meetings Requests Audits Management Training
QbD&PAT TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
47
Weexpect
toomuchin
1yearand
notenough
in10.
QbD&PAT TheScientistIsNoLongerIn
TheLaboratory,ButIntegratedInThe
OverallQualityProcess
48
PeterBoogaard
IndustrialLabAutomation
Consultancy&Training
www.IndustrialLabAutomation.com/Publications.php
peterboogaard@industriallabautomation.com
+31(654)263516(cell)
+31(182)379103(land)
PaperlessLabForum
Q&A
QbD&PAT
TheScientistIsNoLongerInTheLaboratory,ButIntegratedInTheOverallQualityProcess
Relevantwhitepapersdownload