Pharmaceutical Quality by Design (QBD)

Pharmaceutical Quality by Design (QBD) is a concept introduced by the International Conference on Harmonization (ICH) Q8 guideline, as a systematic approach to development that begins with predetermined objectives and emphasizes the understanding of production and processes and process control, based on sound science and quality risk management.
The basic concept of QBD is “The Quality cannot be tested into the product, but it should be built into it.”

1. Kushal Saha
MPH/10008/19
Pharmaceutics
Birla Institute Of Technology
Quality by Design

2. Introduction
PharmaceuticalQualitybyDesign(QBD)isaconceptintroduced
bytheInternationalConferenceonHarmonization(ICH)Q8
guideline,asasystematicapproachtodevelopmentthatbegins
withpredeterminedobjectivesandemphasizesthe
understandingofproductionandprocessesandprocesscontrol,
basedonsoundscienceandqualityriskmanagement.
ThebasicconceptofQBDis“TheQualitycannotbetestedintothe
product,butitshouldbebuiltintoit.”
QBD,alsoknownasqualitypurchasingdesignisemergingto
increasethepromiseofprovidingsafeandeffectivemedicinesto
customersandpromisestoimprovetheefficiencyofproduct
quality.

3. QBD DEVELOPMENT PROCESS INCLUDE
•Beginwithatargetproductprofilethatdescribestheuse,
safetyandefficacyoftheproduct
•Defineatargetproductqualityprofilethatwillbeusedby
formulatorsandprocessengineersasaquantitativesurrogate
foraspectsofclinicalsafetyandefficacyduringproduct
development
•Gatherrelevantpriorknowledgeaboutthedrugsubstance,
potentialexcipientsandprocessoperationsintoaknowledge
space.
•Designaformulationandidentifythecriticalmaterial(quality)
attributesofthefinalproductthatmustbecontrolledtomeet
thetargetproductqualityprofile.
•Designamanufacturingprocesstoproduceafinalproduct
havingthesecriticalmaterialsattributes.

4. Cont..
•Identifythecriticalprocessparametersandinput(raw)material
attributesthatmustbecontrolledtoachievethesecritical
materialattributesofthefinalproduct.Useriskassessmentto
prioritizeprocessparametersandmaterialattributesfor
experimentalverification.Combinepriorknowledgewith
experimentstoestablishadesignspaceorotherrepresentation
ofprocessunderstanding.
•Establishacontrolstrategyfortheentireprocessthatmay
includeinputmaterialcontrols,processcontrolsandmonitors,
designspacesaroundindividualormultipleunitoperations,
and/orfinalproducttests.Thecontrolstrategyshouldencompass
expectedchangesinscaleandcanbeguidedbyarisk
assessment.
•Continuallymonitorandupdatetheprocesstoassureconsistent
quality.

5. LAY OUT OF QUALITY BY DESIGN

6. Opportunities
•Efficient,agile,flexiblesystem
•Increasemanufacturingefficiency,reducecostsandproject
rejectionsandwaste
•Buildscientificknowledgebaseforallproducts
•Betterinteractwithindustryonscienceissues
•Ensureconsistentinformation
•Incorporateriskmanagement
FDAreport“PharmaceuticalcGMPsforthe21stCentury:ARisk-
BasedApproach”hasmadeitimperativetouseQBDapproach
inpharmaceuticals.TounderstandQBDwell,wehaveto
understandmainguidelinesprescribedbyICH-
ICH-Q8:(PharmaceuticalDevelopment)and
ICH-Q9:(QualityRiskManagement)
ICH-Q10:(PharmaceuticalQualitySystem)

7. ICH Q8
Thisguidelinedescribesthesuggestedcontentsforthe3.2.P.2
(PharmaceuticalDevelopment)sectionofaregulatory
submissionintheCommonTechnicalDocument(CTD)format.
Objectives:
•Todesignaqualityproductanditsmanufacturingprocessto
consistentlydelivertheintendedperformanceofthe
product.
•Providescientificunderstandingtosupportthe
establishmentofthedesignspace,specifications,and
manufacturingcontrols.
Quality
by
testing

8. QBD approach, combining design space development and risk management tools

9. Comparison between
the traditional and QBD
Approach
(ICH Q8 guideline)

10. Elements of Pharmaceutical development
QBDcomprisesallelementsofpharmaceuticaldevelopment
mentionedintheICHguidelineQ8.Todesignaqualityproductand
itsmanufacturingprocesstoconsistentlydelivertheintended
performanceofproductistheaimofpharmaceutical
development.
Differentelementsofpharmaceuticaldevelopmentinclude-
Defininganobjective
Determinationofcriticalqualityattributes(CQA)
Riskassessmentanddesignspace
Developmentofexperimentaldesign
Designingandimplementingcontrolstrategy
Continuousimprovement.

11. Advantages of QBD
Betterunderstandingoftheprocess.
Lessbatchfailure.
Moreefficientandeffectivecontrolofchange.
Returnoninvestment/costsavings.
Reductionofpost-approvalsubmissions.
Lessintenseregulatoryoversightandlesspost-approval
submissions.
Moredrugavailabilityandlessrecallandimprovedyields,
lowercost,lessinvestigations,reducedtesting,etc.
Continuousimprovementoverthetotalproductlifecycle.
Contributessubstantiallytorealizethebetter,cheaperand
safermandate.

12. Disadvantages of QBD
Internalunwillingnessincompany
Lackofbeliefinabusinesscase.ItisassumedthatQBD
wouldrequiremoretimetofilegenericproductsorthatthe
amountofclinicaltrialsnecessarytoimplementQBDfor
drugsubstanceproduction
Lackoftechnologytoimplement.
Alignmentwiththirdparties.
InconsistenttreatmentofQBDacrossFDA.Itisbelieved
thatFDAmaynotreviewfilingsinaconsistentmanner.
Lackofconcreteguidanceforindustry.

13. Conclusion
QBDhasgainimportanceintheareaofpharmaceutical
processeslikedrugdevelopment,formulations,analytical
methodandbiopharmaceuticals.Themainreasonbehind
adoptionofQBDistheregulatoryrequirements.
Pharmaceuticalindustryneedsaregulatorycompliancesoas
togettheirproductapprovedformarketing.NeverthelessQBD
approachgivesqualityproductwithcosteffectiveprocedures
andthatisthebasicneed.Movingwithindesignspacewould
notrequirepostapprovalchangestherebyreducingthecost
involved.

14. References
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15. Thank You