1) The document presents an overview of Quality by Design (QbD) in pharmaceutical development. It defines QbD, compares the current and QbD approaches, and outlines the benefits, objectives, and elements of QbD. 2) The key elements of QbD discussed are defining objectives, determining critical quality attributes, risk assessment, experimental design, control strategy, and continuous improvement. Ishikawa and risk assessment methods are also summarized. 3) Implementing QbD provides quality medicines to patients, production improvements for manufacturers, and greater confidence for drug regulators by ensuring predefined product quality objectives.

1. Presented By: Ashish Rajendra Chaudhari
M-pharm Ist year

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c
• Definition of Qbd
• Current vs Good approach to
pharmaceutical development
• Benefits of Qbd
• Objectives of Qbd
• Element of Qbd
• Ishikawa diagram
• Conclusion
• Reference
Content...

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The Quality Mantra....
“Quality can not be tested into products;
It has to be built in by design”
Dr. Joseph M. Juran.

4. Definition of QbD:
ICH Q8,QbD has been defined as
“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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• PART I:
PHARMACEUTICAL DEVELOPMENT
• PART II:
ANNEX TO PHARMACEUTICAL
DEVELOPMENT

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2.1 Components of the Drug Product
2.1.1 Drug Substance
2.1.2 Excipients
2.2 Drug Product
2.2.1 Formulation Development
2.2.2 Overages
2.2.3 Physicochemical and Biological Properties
2.3 Manufacturing Process Development
2.4 Container Closure System
2.5 Microbiological Attributes
2.6 Compatibility

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2.1 Quality Target Product Profile
2.2 Critical Quality Attributes
2.3 Risk Assessment: Linking Material Attributes and
Process Parameters to Drug Product CQAs
2.4 Design Space
2.4.1 Selection of Variables
2.4.2 Describing a Design Space in a Submission
2.4.3 Unit Operation Design Space(s)
2.4.4 Relationship of Design Space to Scale and Equipment
2.4.5 Design Space Versus Proven Acceptable Ranges
2.4.6 Design Space and Edge of Failure
2.5 Control Strategy

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ICH
Q8
ICH
Q9
ICH
Q10
ICH
Q11
QbD
QbD and ICH Guidelines
Pharmaceutical
development
Quality Risk
Management
Pharmaceutical
Quality System
Development &
mfg of drug
substance

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The Important terms related with QbD that are defined in ICH
Q8
Design space : The multidimensional combination and
interaction of input variable (e.g. Material attribute) and process
parameter that have been demonstrated to provide assurance of
quality.
PAT( Process Analytical Technique) : A system for
designing, analyzing, and controlling manufacturing through timely
measurements (i.e. during processing ) of critical quality and
performance attribute of raw and in-process with goal of ensuring
final product quality.

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Current Approach QbD Approach
Quality assured by testing and
inspection.
Quality built into product & process by
design based on scientific
understanding
Control strategy by testing and
inspection
Risk based control strategy
Use of statistical process control unit
method is limited
Use of statistical process control unit
method is predominant
Empirical development Systematic development
Product specification are primary
means of control
Product specification are of the overall
quality summary
Validation of manufacturing process is
primarily based on initial full-scale
batches
Life cycle approach to validation of
manufacturing process and continuous
verification
Frozen process Flexible process within design space
allowing continuous improvement
Current Vs. QbD Approach to Pharmaceutical
Development
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11. Benefits of QbD:
• Less validation burden.
• Better design of product.
• Fewer problems in manufacturing.
• Understanding and mitigation of risk.
• A reduction in overall cost of manufacturing.
• More efficient technology transfer to manufacturing.
• Enabling continuous improvement.
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12. Objectives of QbD :
• To encourages pharmaceutical companies to develop
sufficient understanding of their products and manufacture
processes.
• To ensure that their processes are robust.
• To demonstrate this enhanced understanding to the
pharmaceutical regulatory agencies.
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13. Advantages of QbD:
• Patient safety and product efficacy are focused.
• Scientific understanding of pharmaceutical process and
methods is done.
• It involve product design and process devlopement.
• Science based risk assessment is carried.
• Critical quality attributes are identified and their effect on final
quality of product is analysed.
• It offers robust method or process ..
• Method design concept helps to avoid cost involved with post
approval changes.
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14. Elements of QbD
Define an Objective
Determination of Critical Quality Attributes
(CQA)
Risk Assessment
Development of Experimental Design
Designing and Implementing Control
Strategy
Continuous Improvements
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15. Define an objective:
As per ICH guideline Q8 R2 Quality Target Product Profile can be
defined as “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 realised”.
The Quality target product profile forms the basis for design and the
development of the product .
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16. Intended use in clinical setting, route of administration, dosage
forms, delivery system.
Dosage strength (s), container closure system.
Therapeutic moiety release &
pharmacokineticcharacteristics (e.g., dissolution, aerodynamic
performance).
Drug product quality criteria like sterility, purity, stability
& drug release as appropriate for dosage from the intended
for marketing.
Consideration for the Quality Target Product
Profile (QTPP):
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17. Determination of Critical Quality Attributes
(CQA)
According to ICH Q8 R2 “A CQA is a physical, chemical,
biological, or, microbiological property or characteristics that
should be within an appropriate limit, range, or distribution to
ensure the desired product quality.
CQAs are generally linked with the drug substance, excipients
intermediates and drug products.
It is stated in ICH Q9 that in case of potential drug substance
CQAs are used to guide process development.
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18. Risk Assessment:
Risk assessment consist of the identification of hazards and analysis
an evaluation of risk associated with exposure to those hazards.
Principle of management are:
• Scientific knowledge based evaluation of the risk to quality which
eventually link to the protection of the patient.
• Adequate effort should be taken; formality and documentation of
the quality risk management process should be done with the level
of risk involved
• It is joint responsibility of quality unit, business development,
engineering, regulatory affairs production operations, sales and
marketing, legal, statistics and clinical department.
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19. Methods of Risk Assessment
Methods of risk assessments are mentioned in ICH guideline Q9as
follows:
• Failure mode effects analysis (FMEA)
• Failure mode, effects and critically analysis (FMCEA)
• Fault tree analysis (FTA)
• Hazard analysis and critical control points (HACCP)
• Hazard operability analysis (HAZOP)
• Preliminary hazard analysis (PHA)
• Risk ranking and filtering
• Supporting statistical tools.
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21. Development of Experimental Design
• Experimental design is the multidimensional
combination and interaction of input variables and
process parameters that have demonstrated to provide
assurance of quality.
• Pharmaceutical development scientist have just began to
making use of computer-aided process design (CAPD)
and process simulation to support process development
and optimization of manufacturing.
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22. Designing and implementing control strategy
Control strategy is required to ensure that material and process is
within the expected lower and upper limits. parameter and material
are routinely controlled during production in order to assurer
reproducibility.
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23. Continuous Improvements
• Product quality can be improved throughout the product
lifecycle; companies have opportunities to inventive approaches to
improve quality.
• Process performance can be monoitored to make sure
consistency in quality.
• The QbD approach avails the continuous improvement
throughout product life cycle this is distinguish point from the
conventionl method which must frozen process.
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25. CONCLUSION
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• Quality by Design (QbD) is increasingly becoming an important
and widely used technique in pharmaceutical development.
• It means designing and developing formulations and
manufacturing processes to ensure predefined product quality
objectives.
• Implementing QbD concept in product development provide
quality medicines to patients, production improvements to
Manufacturers with significantly reduced batch failures and drug
regulatory bodies will have greater confidence in the robust
quality of products they are being asked to approve. As such QbD
ng a promising scientific tool in quality assurance in pharma
industry.

26. References
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• Sangshetti, J.N., Zaheer, Z., Mahaparale P.R., Chitlange S.S.,
August 2015, Quality By Design In Pharmaceuticals, Published
By Unique Publication, First Edition, Pp. 12-20,30-44,113-114.
• Jaiprakash N. Sangshetti A, Mrinmayee Deshpande A, Zahid
Zaheer A, Devanand B. Shinde B, Rohidas Arote C, Feb 2014
Review Article Quality By Design Approach: Regulatory Need,
Arabian Journal Of Chemistry
• ICH Q8 (R1) Pharmaceutical Development: Quality By
Design, May 2006.
• Ich Harmonised Tripartite Guideline, November 2005. Quality
Risk Management Q9.

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