This document discusses key concepts of Quality by Design (QbD) including: - QbD was first outlined by quality expert Joseph Juran and emphasizes removing failures to create customer satisfaction and designing in quality. - The ICH definition of QbD is a systematic approach to development beginning with predefined objectives and emphasizing product and process understanding. - ICH Q8, Q9, and Q10 provide guidance on applying science and risk-based approaches to pharmaceutical development and quality systems. - QbD represents a paradigm shift from "quality by testing" to designing quality in based on an understanding of materials, processes, and how they impact critical quality attributes.

1. ARUN KUMAR JAIN
Quality by Design

2. Overview
 Interpretations of Quality
 QbD-Juran
 QbD-Definition
 ICH Q8-10
 Paradigm Shift
 QbD Attributes
 Challenges
 Tools
 Design Space
 QbD –Pharmaceutical Development

3. Interpretations of Quality
Time
Cost
Fitness for use
Performance
Features
Look & Feel

4. Joseph M Juran- QbD
 Quality by Design (QbD) is a concept first
outlined by quality expert Joseph M. Juran
 Joseph Moses Juran (December 24, 1904 – February
28, 2008) was a Romanian-born American engineer and
management consultant
 The word "quality" as having two meanings:
 Features that create customer satisfaction
 The reliability of those features.
 Failures in features create dissatisfactions, so removing
failures is the purpose of quality improvement, while
creating features is the purpose of quality by design

5. Definition of 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 on sound science
and
quality risk management

6. 6
Q10Q8
Q8, Q9 & Q10
Process
Materials
Design
Manufacturing
Distribution
Patient
Facilities
Opportunities to impact
risk using quality risk
management
Q9

7. Pharmaceutical Development - Q8(R2)
 Describes science and risk-based approaches for
pharmaceutical product and manufacturing
process development
 Introduced concepts of design space and flexible
regulatory approaches
 Introduced concepts of Quality by Design (QbD)
and provided examples of QbD development
approaches and design space

8. © ICH, November 2010
Quality Risk Management Process - Q9
Process
Development
Control Strategy
Development
Continual
Improvement
of the product

9. Q10-Pharmaceutical Quality System
The product lifecycle includes the following
Technical activities for new and existing products:
Pharmaceutical Development:
Drug substance development;
Formulation development (including container/closure system);
Manufacture of investigational products;
Delivery system development (where relevant);
Manufacturing process development and scale-up;
Analytical method development.
Technology Transfer:
New product transfers during Development through Manufacturing;
Transfers within or between manufacturing and testing sites for
marketed products.

10. Paradigm Shift

11. Quality by Testing

12. Quality by Design

13. “Quality can not be tested into
products;
it has to be built in
by design”

14. From
‘blind compliance’ to
‘science and risk based
compliance’
Ajaz Hussain, FDA
The Paradigm Change

15. ICH Q8, Q9 and Q10 Working Together
Formulation Activities:
• QTPP Definition
• Pre-Formulation Studies
• Formulation Screening
• Optimization & Selection
Process Development Activities:
• Process Screening
• Lab Scale Development
• Scale-Up Studies
Manufacturing Activities:
• Commercial Scale
Manufacturing
• Batch Release
• Continual Verification &
Improvement
Q8
PharmaceuticalDevelopment
Q9
QualityRiskManagement
Q10
PharmaceuticalQualitySystems

16. • End User
Requirements
QTPP
• Output
Specifications
CQA • Input
Specifications
CMA
• Process
parameters
CPP
QbD Terminologies

17. QTPP-Quality Target Product Profile
 Indented Use in Clinical
Setting
 Route of Administration
 Dosage Form
 Delivery Systems
 Dosage Strength
 Container closure system
 Drug Product Quality Criteria:
Sterility, Purity, Stability etc.

18. Target Quality Profiling-
A Perspective
Customer
Market
Regulations
Research
Engineering
Business insights
Manufacturability
Installation &
Service
Purchasing
Suppliers
Competitor(s)
Corporate
Social
Responsibility
HRM)

19. Critical Quality Attributes (CQAs)

20. Critical Material Attributes (CMAs)
 Input Material Quality Attributes
 Raw material Quality
 Examples: Water Content/LOD, Assay, Impurities,
Colour Value

21. Relation between CMA, CPP and CQA

22. Process
(or Process Step)
Design
Space
Monitoring of
Parameters
or Attributes
Process Controls/PAT
Input
Process
Parameters
Input
Materials
Product
(or Intermediate)
Product
Variability
Reduced
Product
Variability
Process
Variability
Reducing product Variability

23. What We Need?

24. Key
in the Future of
Manufacturing
Process Understanding

25. A Process is well understood when…
 all critical sources of variability are identified and
explained;
 variability is managed by the process; and,
 product quality attributes can be accurately and
reliably predicted over the design space …
http://www.fda.gov/cder/guidance/6419fnl.ht
m

26. Challenges to ‘Understanding’
 Understanding involves Measurements

27. Challenges to Analytical Science
The need for increased
Process understanding is
a massive Boost for
Analytical Science

28. Fritz Erni
Challenges to Analytical Science
adequate Tools?

29. Product Development Tools
 Computer-aided drafting software
 Solid modeling software
 Finite element analysis software
 Parametric analysis software
 Rapid prototyping techniques
 Design for manufacture and assembly techniques
 Failure mode and effect analysis

30. Production Tools
 Computer-aided Manufacturing
 Computer numerical controlled tools
 Continuous process improvement
 Just-in-time production
 Virtual manufacturing software
 Agile manufacturing

31. Statistical Tools
 Design of Experiments
 Statistical Process Control

32. Other Considerations
 Training is a must
 Requires money and time
 Using the tools increases employee retention and
satisfaction

33. PAT: Process Understanding
 Improved Process Knowledge to Identify and Remove
Sources of Variability
 Identify Critical to Quality parameters
 Process understanding as input to Risk Management
 Control what is critical

34. 34
Design space
Independent
Factor
Space
Dependent
Response
Space
f(x)=?
“Linkage”

35. DOE and Design Space
 DOE is a tool to develop the design space.
 The outcome of the DOE
 Identifies the model correlations between CPPs/CMAs and CQAs
 Helps in establishing the boundaries of the design space.
 DOE can be used for Scale-up activities.
 DOE can be used as tool for confirming the design space at
manufacturing scale.

36. Plackett Burman Design-Screening
Run A B C D E F G H I J K
1 - - - - - - - - - - -
2 + - - - + - + + - + +
3 + + - - - + - + + - +
4 + + + - - - + - + + -
5 - + + + - - - + - + +
6 + - + + + - - - + - +
7 + + - + + + - - - + -
8 - + + - + + + - - - +
9 + - + + - + + + - - -
10 - + - + + - + + + - -
11 - - + - + + - + + + -
12 - - - + - + + - + + +
- means low, + means high level

37. 37
Design Space
 FACTOR SPACE
 N dimension X’s
 X1
 X2
 X3
 X4
 X5
 XN
 RESPONSE SPACE
 M dimension Y’s
 Y1
 Y2
 Y3
 Y4
 Y5
 YM

38. Inputs: Outputs:
P1
P2
P3
M1
M2
CQA1
CQA2
CQA3
Relationships:
CQA1 = function (M1)
CQA2 = function (P1, P3)
CQA3 = function (M1, M2, P1)
P2 might not be needed in the
establishment of design space
Process
Parameters
Material Attributes
Critical
Quality
Attributes
Source:MohebNasr,FDA

40. Design Space Vs Changes

43. Process Performance /
Product Performance
 Control Charts
 Performance Indicators