The document discusses Quality by Design (QbD) in the pharmaceutical industry. It defines QbD and outlines its key benefits, including higher product quality assurance, cost savings, and regulatory flexibility. The main elements of QbD are described as identifying target quality profiles, critical quality attributes, risk assessment, linking attributes and parameters to quality, defining a design space and control strategy. QbD facilitates innovation and continuous improvement across a product's lifecycle.

1. Presented By :-
Chinmay H. Gramopadhye
1st M.Pharm QA
Guided By :
Prof. Ms.V.V. Kunjir
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2.  INTRODUCTION
 NEED OF QBD
 BENEFIT FOR INDUSTRY
 OBJECTIVES
 KEY ELEMENTS
 CONCLUSION
 REFERENCE
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3.  Quality by Design (QbD) has become a new concept for
development of quality pharmaceutical products, It is an essential
part of the modern approach to pharmaceutical quality, QbD is a
best solution to build a quality in all pharmaceutical products.
 “Quality by Design means designing and developing
manufacturing processes during the product development stage to
consistently ensure a predefined quality at the end of the
manufacturing process.”
 The FDA publication defined Quality by Design as:
Developing a product to meet predefined product quality, safety
and efficacy
Designing a manufacturing process to meet predefined product
quality, safety and efficacy
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4.  Definitions:
Quality :
“The suitability of a drug either substance or drug product for its
intended use. This term includes such attributes as the identity,
strength, and purity.”(ICH Q8)
Quality by Design:
“It is a systematic approach to development that begins with
predefined objectives and emphasizes product and process
understanding and process control, based on sound science and
quality risk management”
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5.  a. Development of new molecular entity
· Preclinical study.
· Nonclinical study.
· Clinical Study.
· Scale up.
· Submission for market Approval
 b. Manufacturing
· Design Space.
· Process Analytical Technology.
· Real time Quality Control.
 c. Control strategy
· Risk based decision.
· Continuous Improvement.
· Product performance
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6.  Higher level of assurance of product quality
 Cost saving and efficiency for industry and regulators
 Facilitate innovation to address unmet medical needs
 Increase efficiency of manufacturing process and reduce
manufacturing cost and product rejects
 Minimize/eliminate potential compliance actions, costly
penalties and recalls
 Enhance opportunities for first cycle approval
 Streamline post approval manufacturing changes and regulatory
processes
 More focused PAI and post approval cGMP inspections
 Opportunities for continual improvement
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7.  Eliminate batch failures
 Minimize deviations and costly investigations
 Avoid regulatory compliance problems
 Empowerment of technical staff
 Efficient, agile, flexible system
 Increase manufacturing efficiency, reduce costs and project
rejections and waste
 Build scientific knowledge base for all products
 Better interact with industry on science issues
 Ensure consistent information
 Incorporate risk management
 Reduce end-product testing
 Speed-up release decision
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8.  To facilitate innovation and continuous improvement
throughout the product lifecycle
 To provide regulatory flexibility for specification setting and
post-approval changes
 To streamline the submission and review processes
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9. 1. Identify the Target Product Profile
2. Critical Quality Attributes (CQAs)
3.Perform a Risk (Assessment) Analysis
4. Link the drug and excipient attributes and the process
parameters to the CQAs
5. Define the Design Space
6. Define the Control Strategy
7. Product lifecycle management & continual improvement
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10. 1. Define Target Product Quality Profile (TPQP):
 “Prospective and dynamic summary of the quality
characteristics of a drug product that ideally will be achieved to
ensure that the desired quality, and thus the safety and efficacy,
of a drug product is realized”.
 Considerations for the quality target product profile could
include:
 Intended use in clinical setting, route of administration,
dosage form, delivery systems;
 Dosage strength(s);
 Container closure system;
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11. Therapeutic moiety release or delivery and attributes affecting
pharmacokinetic characteristics (e.g., dissolution,
aerodynamic performance) appropriate to the drug product
dosage form being developed;
Drug product quality criteria (e.g., sterility, purity, stability
and drug release) appropriate for the intended marketed
product.
TPQP is related to identity, assay, dosage form, purity,
stability in the label .
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12. 2. Critical Quality Attributes (CQAs):
A CQA has been defined as “a physical, chemical, biological, or
microbiological property or characteristic that should be within
an appropriate limit, range, or distribution to ensure the desired
product quality”.
CQAs are generally associated with ;
raw materials (drug substance, excipients),
intermediates (in-process materials),
 drug product.
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13. For Drug Substance
(chemical)
For Drug product
(tablet)
Appearance
Particle size
Morphic forms
Water content
Residual solvents
Organic impurities
Inorganic impurities
Heavy metals
Residue on ignition
Assay
Appearance
Identification
Hardness
Uniformity of dosage
Physical form
Dissolution
Degradation products
Water content
Assay
Microbiological limits
Example;
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14. 3. Risk Assessment :
 The FDA defines a Risk Management as, a strategic safety
program designed to decrease product risk by using one or more
interventions or tools.
 It is systematic process for the assessment, control,
communication and review of risks to the quality of the drug
product across the product lifecycle.
 Quality Risk Management provides a structure to initiate and
follow a risk management process.
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17. Risk Assessment Tools:-
 Failure mode effects analysis (FMEA):
It is a systematic and proactive method to identify and
mitigate the possible failure in the process.
 Failure Mode, Effects and Criticality Analysis (FMECA):
In FMECA, each failure mode of the product is identified and
then evaluated for criticality. This criticality is then translated
into a risk, and if this level of risk is not acceptable, corrective
action must be taken.
 Fault tree analysis (FTA):
This tool assumes failure of the functionality of a product or
process.
 Hazard analysis and critical control points (HACCP):
HACCP provides detailed documentation to show process or
product understanding through identifying parameters to
control and monitor.
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18. 4. Critical Process Parameters(CPPs):
“A critical process parameter (CPP) is defined as parameter
whose variability has an impact on CQA and therefore should
be monitored and controlled to ensure process produces desired
quality.”
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19. Operation During Tableting Critical Process Parameter
Wet granulation 1.Mixing time, 4. Impeller speed
2.Binder fluid addition rate & time
3.Method of binder addition, 5.Temperature
Drying 1.Drying time
2.Inlet air flow
3.Exhaust air temperature & flow
Milling 1.Milling speed
2.Screen size
3.Feeding rate
Mixing 1.Mixer type
2.Mixing time
3.Order of addition
Compression 1.Pre compression force 5.Main compression force
2.Dwell time 6. Hopper design
3.Punch penetration depth 7.Roller type
4. Auger screw rate 8.Ejection force
Coating
1.Inlet air flow 3.Time
2.Temperature 4.Spray pattern & rate
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20. 5.Design Space : -
ICH Q8(R2) defines design space as “ the multidimensional
combination and interaction of input variables (e.g., material
attributes) and process parameters that have been demonstrated
to provide assurance of quality.
Working within the design space is not considered as a change.
Movement out of the design space is considered to be a change
and would normally initiate a regulatory post approval change
process. X
Example : TPQP % Dissolution
CPP Z Y CMA
Drying time Conc. Raw material
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21. 6.Control strategy :
 ICH Q10 defines a control strategy as “a planned set of controls
derived from current product and process understanding that
assures process performance and product quality.
 A control strategy can include, but is not limited to, the
following:
 Control of input material attributes (e.g., drug substance,
excipients, primary packaging materials) based on an
understanding of their impact on processability or product
quality;
Product specification(s);
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22. Controls for unit operations that have an impact on
downstream processing or product quality
(e.g., the impact of drying on degradation, particle size
distribution of the granulate on dissolution);
In-process or real-time release testing in lieu of end-product
testing
(e.g. measurement and control of CQAs during processing);
 A monitoring program
(e.g., full product testing at regular intervals) for verifying
multivariate prediction models.
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23.  Conclusion :
 Quality by design is an essential part of the modern approach
to pharmaceutical quality.
 The goal of QbD is to reduce product variability and defects,
thereby enhancing patient efficacy and safety
 Reduce product recalls and compliance actions, resulting in
cost savings for pharmaceutical companies.
 QbD methodology helps in identifying and justifying target
product profiles, product and process understanding.
 Helps in continuous improvement.
 There is a need for vigorous and well funded research
programs to develop new pharmaceutical manufacturing
platforms.
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24. 1. Juran JM. Juran on Quality by Design :The new step for planning
quality into goods and services. New York : The Free Press; 1992
pg.no 1-2
2. Woodcock J, The concept of pharmaceutical quality, American
Pharmaceutical Review, 7(6), 2004, 10-15.
3. ICH Q8 (R1) — Guidance for Industry Pharmaceutical Development
Revision 1 November 2007
4. ICH Q9- Quality risk management , 2006
5. ICH Q10: Pharmaceutical Quality System, 2007.
6. US FDA – Guidance for Industry - Nov 2009 ICH Revision 2
7. European Medicinal Agency -ICH guideline Q8 (R2) on
pharmaceutical development 2004
8. Blog On QbD in pharmaceutical industry by DR Anthony Melvin
Crasto, Worlddrugtracker , www.allfordrugs.com/ qbd-in-
pharmaceutical-industry/
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