Pharmaceutical Quality by Design (QbD)

The pharmaceutical Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based sound science and quality risk management.

1. QUALITY BY DESIGN
Department of Pharmaceutical Quality Assurance
Anupriya N. R

2. CONTENTS
Introduction
Definition
QbD for Drug products, Drug substances & Excipients
Analytical QbD
Quality by Design Tools
Conclusion
References
2

3. Introduction
TheconceptofQbDwasmentionedintheICHQ8
guideline,whichstatesthat“qualitycannotbetested
intoproducts,i.e.,qualityshouldbebuiltinby
design”.
QbDencompassesdesigninganddeveloping
formulationsandmanufacturingprocesseswhich
ensurespredefinedproductspecifications.
3

4. Quality by Design
ThepharmaceuticalQualitybyDesign(QbD)is
asystematicapproachtodevelopmentthat
beginswithpredefinedobjectivesand
emphasizesproductandprocessunderstanding
andprocesscontrol,basedsoundscienceand
qualityriskmanagement.
4

5. 5

6. Why QbD?
Higherlevelofassuranceofproductquality.
Costsavingandefficiencyforindustry&regulators.
Enhanceopportunitiesforfirstcycleapproval.
Streamlinepostapprovalchanges&regulatory
processes.
Morefocusedinspections.
Opportunitiesforcontinualimprovement.
6

7. ICHGuidelinesOverview
7

8. QbD for Drug products, Drug substances &
Excipients
8

9. Elements of Quality by Design
9

10. Target Product Profile
Summaryofthequalitycharacteristicsofadrug
producttoensuresafetyandefficacy.
Includes,butnotlimitedto:
Dosageform
Routeofadministration
Pharmacokineticcharacteristics
„e.g.,dissolution,aerodynamicperformance
Qualitycharacteristicsforintendeduse
e.g.,sterility,purity
10

11. TPP VS QTPP
Target Product Profile Quality Target Product Profile
--Description
–Clinical Pharmacology
–Indications and Usage
–Contraindications
–Warnings
–Precautions
–Adverse Reactions
–Drug Abuse and Dependence
–Over dosage
–Dosage and Administration
–How Supplied
–Animal Pharmacology and/or
Animal Toxicology
–Clinical Studies
–Dosage Form
–Appearance
Shape, size etc.
–Identity
–Strength
–Assay
–Uniformity
–Purity/Impurity
–Stability, and
–Dissolution/Disintegration
Pharmacokinetics and
bioequivalence
11

12. Critical Quality Attributes (CQAs)
Physical,chemical,biologicalormicrobiological
propertyorcharacteristic.
„Drugproduct,drugsubstance,intermediates,and
excipientscanpossessCQAs.
oDirectlyaffectproductquality.
oAffectdownstreamprocessability.
DrugproductCQAsaffectproductquality,safety,
and/orefficacy.
oAttributesdescribingproductpurity,potency,stability
andrelease.
oAdditionalproductspecificaspects(e.g.,adhesive
forcefortransdermalpatches).
12

13. Risk Assessment
Toolsforparameterscreening
Examples:Ishikawadiagrams,What-ifanalysis,
HAZOPanalysis
Toolsforriskranking„
Examples:FMEA/FMECA,Paretoanalysis,Relative
ranking
Experimentaltoolsforprocessunderstanding
Examples:Statisticallydesignedexperiments(DOE),
mechanisticmodels
13

14. Design Space
Themultidimensionalcombinationandinteractionof
inputvariables(e.g.,materialattributes)andprocess
parametersthathavebeendemonstratedtoprovide
assuranceofquality.
Adesignspacemaybeconstructedforallunit
operations,orforthespecificunitoperations.
14

15. Design Space Determination
First-principles approach
Non-mechanistic/empirical approach
Scale-up correlations
„Risk Analysis
„Any combination of the above
15

16. Describing Design Spaces
Linear Ranges of Parameters
„Mathematical Relationships
Time-dependent functions
Combinations of variables
e.g., Principle components of multivariate
model
Scaling Factors
Single or multiple unit operations
16

17. Control Strategy
Controlstrategyisdefinedas“aplannedcontrol
operations,derivedfromcurrentproductandprocess
understandingthatassuresprocessperformanceand
productquality”.
Thecontrolstrategycanincludethefollowing
elements:
proceduralcontrolsprocessinprocessqualitycontrols,lot
releasetesting,processmonitoring,physicalcharacterization,
comparabilitytestingandageingstudies.
Inputmaterialcontrols,processparameters,process
operationsandmonitoring,designspacesaroundindividual
ormultipleunitoperations,andorfinalproductspecifications
usedtoensureconsistentquality.
17

18. Life Cycle Management
Amonitoringprogramforverifyingthevalidityof
processmodelsshouldbeestablishedandbebasedon
ariskanalysisofthemodelitselfandincludes
possiblewaystoverifythemodelbyanothermeans.
Continuousimprovementisanessentialelementina
modernqualitysystemthataimsatimproving
efficiencybyoptimizingaprocessandeliminating
wastedeffortsinproduction.
18

19. Analytical QbD
19

20. QbD Approach for Analytical
methods
ICHQ8doesn’texplicitlydiscussanalyticalmethod
development.
However,conceptsapply:
ApplicationofscienceandRiskbasedmethodology
Systematicapproachthatincludes:Riskassessment,
definingaDesignspace,ControlStrategyand
continualimprovementtoincreasesmethod
robustnessandunderstanding.
20

21. Variation of Analytical Method
Many Factors can affect analytical results.
21

22. Elements of analytical QbD
Target Measurement
Select Technique
Risk assessment
Method Develop/ Validation
Control strategy
Continual Improvement
22

23. Benefits of Analytical QbD
Development of a robust method
Applicable throughout the life cycle of the product
Regulatory flexibility
23

24. Quality by Design Tools
Design of experiments (DoE)
Risk assessment
Process analytical technology (PAT)
24

25. Design of Experiment (DoE)
Asystematic,plannedapproachtosolvingproblems
bygaininginformationthroughcarefullyplanned
experimentsorstudies.
Thesestudieshaveadequatestatisticalpropertiesto
beableto:
accuratelymeasuretheeffectsofformulation&
processfactorsonthekeyresponsevariable(s)(i.e.,
dissolution,contentuniformity,etc.)
tellifthesefactoreffectsarereal(abovethenoise
level)andifsotoaccuratelyquantifytheseeffects.
25

26. Process Analytical Technology (PAT)
Asystemfordesigning,analyzing,andcontrolling
manufacturingthroughtimelymeasurements(i.e.,
duringprocessing)ofcriticalqualityandperformance
attributesofrawandin-processmaterialsand
processeswiththegoalofensuringfinalproduct
quality.
ThetermanalyticalinPATisviewedbroadlyto
includechemical,physical,microbiological,
mathematical,andriskanalysisconductedinan
integratedmanner.
26

27. Risk Assessment
Asystematicprocessoforganizinginformationto
supportariskdecisiontobemadewithinarisk
managementprocess.Itconsistsoftheidentification
ofhazardsandtheanalysisandevaluationofrisks
associatedwithexposuretothosehazards.
27

28. COMPARISION B/W TRADITIONAL APPROCHES AND QBD
Aspects Traditional QbD
Pharmaceutical
development
Empirical; univariate
Experiments
Systematic; multivariate
experiments
Manufacturing
process
Fixed; validation on 3 initial
full-scale batches; focus on
reproducibility
Adjustable within design
space; continuous verification;
focus on control strategy &
robustness
Process control In-process testing for
go/no-go; offline analysis
w/slow response
PAT utilized for feedback &
feed forward, real time
Product
specification
Primary means of quality
control; based on batch
data
Part of the overall quality
control strategy; based on
desired product performance
Control
strategy
Mainly by intermediate and
end product testing
Risk-based; controls shifted
upstream; real-time release
Lifecycle
management
Reactive to problems &
OOS; post-approval
changes needed
Continuous improvement
enabled within design space

29. Conclusion
Qualitybydesignisanessentialpartofthemodern
reliableconceptandisaninnovativeapproach
towardsthepharmaceuticalquality.
QualitybyDesign
Definetargetproductqualityprofile
Designanddevelopformulationandprocesstomeet
targetproductqualityprofile
Identifycriticalrawmaterialattributes,processparameters,
andsourcesofvariability
Controlrawmaterialsandprocesstoproduce
consistentqualityovertime
29

30. References
KhatriS,SainiS,gangawatK,GurubalajiS.Pharmaceutical
QbD:ConceptsforDrugProductDevelopment.IntJPharm
Sci.2014;26(1):84-91.
S.PatilA,M.PetheA.QualitybyDesign(QbD):Anew
conceptfordevelopmentofqualitypharmaceuticals.IJPQA.
2013;4(2):14-9.
https://www.ich.org/fileadmin/Public_Web_Site/Training/G
CG_Endorsed_Training_Events/APEC_LSIF_JCCT_workshop
_Beijing__China_Dec_08/Day_1/Regulatory_perspective.pd
f(Accessedon23march2019)
https://www.fda.gov/downloads/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDER/UCM 301056.pdf
(Accessedon23march2019)
JosephMJuran,JosephADeFeo.Juran’squalityhandbook.
6thed.McgrawHigherEd.2010:439-466.
30

31. THANK YOU