Role of quality by design (qb d) in quality assurance of pharmaceutical product
Powerpoint TemplatesPage 1Powerpoint TemplatesROLE OF QUALITY BY DESIGN (QbD)IN QUALITY ASSURANCE OFPHARMACEUTICAL PRODUCTPresented by:Dimple lodhaM. Pharm, sgsits
Powerpoint TemplatesPage 2CONTENTS Introduction Definition Traditional Pharmaceutical Quality Assessment System The Current And The Future State Of Quality Management Comparision Of QbD Program With Current Status In QA An Overview Of QbD Process Steps Of QbD Program In Assuring Quality Of P’ceutical Product Quality By Design (QbD) Tools Important Computer Software For Optimization Potential Benefits From QbD Ten Key Challenges For QbD Adoption Conclusion
Powerpoint TemplatesPage 3INTRODUCTION a systematic method relating mechanistic understandingof input material attributes and process parameters todrug product critical quality attributes. accomplished through the use of multivariateexperiments involving modern process controls enablingprocess understanding. QbD-based pharmaceutical manufacturing process willbe adjustable within a design space, providing a robustprocess that is managed with a control strategydeveloped using modern statistical process controlmethods.
Powerpoint TemplatesPage 4DEFINITION The International Conference on Harmonization (ICH)has defined QbD in ICH Q8R as “a systematic approach to pharmaceutical developmentthat begins with predefined objectives and emphasizesproduct and process understanding based on soundscience and quality risk management.”
Powerpoint TemplatesPage 5TRADITIONAL PHARMACEUTICALQUALITY ASSESSMENT SYSTEMConventional Simplified Quality Control Diagram using QbT
Powerpoint TemplatesPage 6CURRENT AND THE FUTURESTATE OF QUALITY MANAGEMENT
Powerpoint TemplatesPage 7COMPARISION OF QbD PROGRAMWITH CURRENT STATUS IN QAAspect Current state Desired QbD statePharmaceuticaldevelopmentEmpirical; univariate Systematic;multivariateManufacturingprocessvalidation on threebatches; focus onreproducibilityAdjustable withindesign space; focuson control strategyProcess control In-process testing PAT utilizationProduct specification based on batch data based on productperformanceControl strategy intermediate and endproduct testingRisk-based; real-timerelease
Powerpoint TemplatesPage 8AN OVERVIEW OF QbD PROCESS
Powerpoint TemplatesPage 9STEPS OF QbD PROGRAM IN ASSURINGQUALITY OF PHARMACEUTICALSControl manufacturing processes to produce consistent quality over timeControl strategy Process capability Maintain consistentquality over timeIdentify Critical Quality Attributes, Process Parameters and Sources ofVariabilityDesign space Source of variabilityDesign Product and Manufacturing ProcessProduct design and development Process design and developmentDefine Target Product Quality Profile
Powerpoint TemplatesPage 10Identifying Target Product QualityProfile (TPQP)The target product profile (TPP) has beendefined as a “prospective and dynamic summaryof the quality characteristics of a drug productthat ideally will be achieved to ensure that thedesired quality, and thus the safety and efficacy,of a drug product is realized”.
Powerpoint TemplatesPage 11CONTD…Quality target product profile for a lyo vial for sterile injectableRequirementIndication Chronic disease (treatment of nervousbreakdown)Dosage form Lyophilisate for solution for injectionDosage strength Nominal dose 20mg/vialAdministration route Subcutaneous (0.8ml)Reconstitution time Not more than 2 minSolution for reconstitution 1ml 0.9% saline (provided by the pharmacy)Shelf life Two yr 2–8 ◦CDrug product requirement Meets pharmacopoeial requirement forparenteral dosage form as well as product specific requirementsStability during administration Reconstituted solution is stable for 24 h atTemperature ≤30 ◦C
Powerpoint TemplatesPage 13Process Design and Development• Defined as outline of the commercialmanufacturing process. It includes:FacilityEquipmentmaterial transfermanufacturing variablescomputer-aided process design (CAPD)process simulation
Powerpoint TemplatesPage 14Identifying CQA and CPP• Critical Quality Attributes (CQA):A CQA has been defined as “a physical, chemical,biological, or microbiological property or characteristicthat should be within an appropriate limit, range, ordistribution to ensure the desired product quality”.• Critical Process Parameters (CPP):• Critical process parameters (CPP) are process inputsthat have a direct and significant influence on criticalquality attributes when they are varied within regularoperation range.•
Powerpoint TemplatesPage 15CONTD.Example of identification of Process Parameters and Material AttributesPrior to Pharmaceutical Development
Powerpoint TemplatesPage 16Design Space Design Space defines the relationship between CriticalQuality Attributes (CQAs) and Critical ProcessParameters (CPPs), and identifies acceptable operatingranges for CPPs. It is the region where acceptableproduct can be produced. Design Space can be considered to be a snap-shot intime representative of the current process knowledge. The Design Space also contains the proven acceptableranges (PAR) for CPPs and acceptable values for theirassociated CQAs.
Powerpoint TemplatesPage 17CONTD.• Methods for presenting design space includes:Graphs (surface-response curves and contourplots)Linear combination of parameter rangesEquationsModels.
Powerpoint TemplatesPage 18CONTD.FIGURE 1 FIGURE 2Response graphs for dissolution are depicted as a surface plot (Figure 1)and a contour plot (Figure 2).
Powerpoint TemplatesPage 19CONTD.FIGURE 3 FIGURE 4Design space for granulation parameterslinear combination of their ranges, (Figure 3)nonlinear combination of their ranges, (Figure 4)
Powerpoint TemplatesPage 20Control strategy• ICH Q10 defines a control strategy as “a planned set ofcontrols derived from current product and processunderstanding that assures process performance andproduct quality. The controls can include parameters andattributes related to drug substance and drug productmaterials and components, facility and equipmentoperating conditions, in process controls, finishedproduct specifications and the associated methods andfrequency of monitoring and control.”
Powerpoint TemplatesPage 21CONTD.• Different levels of control strategies:Level 1: Extensive end product testing + FixedCritical Process ParametersLevel 2: Reduced end product testing + Flexiblemanufacturing process within fixed design spaceLevel 3: PAT, Real-time automatic“engineeringcontrol” + Flexible manufacturing process
Powerpoint TemplatesPage 22QUALITY BY DESIGN (QbB) TOOLSDesign of Experiment:Defining objectives of study and planning theexperimentScreening of factors and factor influence studyResponse surface methodologyFormulation and evaluation of DDSComputer aided modelling and search for an optimumValidation of DOE methodologyScale up and implementation
Powerpoint TemplatesPage 23CONTD. The input variables, which are directly under the controlof the product development scientist, are known asindependent variables e.g., drug content, polymercomposition, compression force, percentage ofpenetration enhancer, hydration volume, agitation speed.Quantitative variablesQualitative variables The characteristics of the finished drug product or the in-process material are known as dependent variablese.g., drug release profile, percent drug entrapment, pelletsize distribution, moisture uptake.
Powerpoint TemplatesPage 24Experimental designs for RSM,screening, and factor influence studies• Factorial designs• Fractional factorialdesigns• Plackett–Burman designs• Star designs• Central compositedesigns• Box–Behnken designs• Equiradial designs• Mixture designs• Taguchi designs• Optimal designs• Rechtschaffner designs• Cotter designs• Center of gravity designs
Powerpoint TemplatesPage 25Product Analytical Technology (PAT)• A desired goal of the PAT framework is to design anddevelop well understood processes that will consistentlyensure a predefined quality at the end of themanufacturing process.• Various tools of PAT are as follows:Multivariate tools for design, data acquisition andanalysisProcess analyzersProcess control toolsContinuous improvement and knowledgemanagement tools
Powerpoint TemplatesPage 26Risk Assessment Risk is defined as the combination of the probability ofoccurrence of harm and the severity of that harm. Risk Assessment is a “systematic process of organizinginformation to support a risk decision to be made within ariskmanagement process”. It consists of the identification of hazards and theanalysis and evaluation of risks associated withexposure to those hazards.
Powerpoint TemplatesPage 28POTENTIAL BENEFITS FROM QbDQuantifiable benefits• Reduction of COGS andcapital expense.• Technical developmentproductivity.• Improved quality andlower risk.• Increased salesNon Quantifiable Benefits• Improved public image• Standardized definitions• Sharing best practices• High quality of reviewsand delivery of regulatorybenefits
Powerpoint TemplatesPage 29TEN KEY CHALLENGES FOR QbDADOPTIONChallenges occur withincompanies• Internal misalignment• Lack of belief in business case• Lack of technology to execute• Alignment with third partiesChallenges are directlyrelated to the FDA• Inconsistency of QbD acrossFDA• Lack of tangible guidance• Regulators not prepared tohandle• Does not inspire confidence• Misalignment of internationalregulatory bodies• Current interaction withcompanies is not conducive toQbD
Powerpoint TemplatesPage 30CONCLUSION“Quality can not be testedintoproducts; it has to be builtIn by design”Joseph M Juran
Powerpoint TemplatesPage 31REFERENCES Sandipan Roy in “Quality by design: A holistic concept of buildingquality in pharmaceuticals”, June 2012, Int J Pharm Biomed Res,100-108 Bhupinder singh, Rahul Batova, Chandra Bhushan Tripathi, RishiKapil in Developing micro/ nano particulate drug delivery systemusing “Design of Experiments” Volume I, Issue 2, April 2011,International Journal of Pharmaceutical Science, 75-87 Bhat,S.“Quality by design approach to cGMP” 2010. Drakulich, A. “Critical challenges to implementing QbD: A Q&A withFDA”, Pharm. Technol, 2009, 90–94. Q8(R1) Pharmaceutical Development Revision 1, 1 -14 Q8(R2) Pharmaceutical ,August 2009 Q9 Quality Risk Management, 4 version, November 2005 Q10 Pharmaceutical Quality System, June 2008