The document introduces Pharmaceutical Quality by Design (QbD), emphasizing a systematic approach to enhance product and process understanding in pharmaceutical development, moving away from traditional testing methods. It outlines the benefits for both manufacturers and regulators, such as improved product quality, reduced time to market, and increased innovation flexibility. Key components of QbD include target product profiles, critical quality attributes, and process parameters, all aimed at ensuring quality through proactive design and risk management.

1. KEY COMPONENTS OF
PHARMACEUTICAL
QUALITY BY DESIGN (QBD)
– AN INTRODUCTION
By
Dr. Saurabh Arora
Managing Director
Auriga Research Limited

2. CONTENTS
 Introduction
 Current approach vs QbD
 Why QbD is Win-Win
 Implications of QbD
 Overview of QbD
 Key Components
 Conclusion

3. HOW DO WE ESTABLISH PRODUCT
QUALITY?
Then and Now

4. HISTORICAL APPROACH TO QUALITY
 No testing required
 Testing of final products
 Testing of ingredients and final product
 Extensive testing of ingredients, final products and
control of process parameters
 Testing and control based on process validation
and strict adherence to process

5. JUST GET FROM A TO B
 Traditional approach focused on achieving
compliance to product specifications
 Only minor variations studied to established that the
product is reproducible
 Not necessarily the best way to get from A to B

6. A BETTER WAY TO CROSS THE RIVER?

7. QBD
 What is the best way to get from A to B?
 What are the other routes can I take to safely get
from A to B?
 It is like having a GPS navigation system for your
product and process!

8. NEW LEVEL OF QUALITY
 Systematic development process
 Moving away from “hit and trial”
 Quality is built into the product not only controlled
by testing

9. CURRENT VS. QBD APPROACH TO
PHARMACEUTICAL DEVELOPMENT
Current Approach QbD Approach
Quality assured by testing and
inspection
Quality built into the product &
process by design, based on
scientific understanding
Data intensive submission –
disjoined information without “big
picture”
Knowledge rich submission –
showing product knowledge &
process understanding
Specifications based on batch
history
Specifications based on product
performance requirements
“Frozen Process” discouraging
changes
Flexible process within design
space, allowing continuous
improvement
Focus on reproducibility – often
avoiding or ignoring variations
Focus on robustness –
understanding and controlling
variations

10. THINK WIN-WIN
QbD is good for both the manufacturers and the
regulators

11. QBD IS WIN-WIN
Wins for the regulator
More pharmaceutical products
approved in shorter timeline
Better quality products
reaching the market
Lower-cost products available
to the consumer
Reduced audit frequency

12. QBD IS WIN-WIN
Wins for the manufacturer
Reduced time to market
Space and flexibility for more innovation
Reduced documentation
Better communication between authorities and
industry
Guaranteed quality for every unit produced
Decreased cost of production by improved
productivity
Competitive advantage in the market
Image improvement
Creating value using existing data and resources
Better knowledge management

13. IMPLICATIONS ON THE
ORGANISATION
Implications on of QbD

14. QBD IMPLICATIONS
QbD
Organization Process
Management
Personnel
QA/QC
IT
Understanding
Technology

15. IMPLICATIONS ON PERSONNEL
 Employees need new skills
 Scientific data analysis
 Statistics
 Process control
 Very similar to 6 Sigma training structure
 Master black belts
 Black belts
 Green belts

16. IMPLICATIONS ON PERSONNEL
 Structural changes might be required
 There might be need for new Department
 There is a need for increased collaboration between
departments and functions
 Increased contact with regulatory authorities
 Clearly defined to accountability roles and responsibility
 Interdisciplinary project team, QA, R&D, IT,
manufacturing

17. IMPLICATIONS ON MANAGEMENT
 Commitment of management
 Initial phase will require more investment, though there
will be saving in the long run.
 Define the QbD development strategy, team, goals,
objectives, commit to resources, expected benefits
 Might be risky to ignore QbD
 Regular review of the progress
 Choice of outsourcing partner
 Ensuring proper communication

18. IMPLICATIONS ON QA
Must be aware of changes in the regulatory
process
 The structure of audits will change
 Scrutiny will challenge scientific understanding of
quality factors and risk mitigation
 More focus on the development Department
 Comparison between real design space and
documented design space
 Documentation of improvements, changes and
deviations

19. IMPLICATIONS ON QA
 Validation
 Validation to focus on management of critical to
quality parameters
 Could be, real-time using PAT instead of three batch
 Better process understanding  Reduced validation
effort
 Software validation
 Documentation
 Better process understanding may change
specifications
 Submissions would need to include design space and
control space

20. LINKING 4 AREAS OF PROCESS
UNDERSTANDING

21. BASIC TERMINOLOGY
Definitions and acronyms

22. WHAT IS PQ?
 What is Pharmaceutical Quality (PQ)?
 According to USFDA –
a product should be called as of pharmaceutical
quality when it is -
 Free of Contamination
 Reproducibly delivers the therapeutic benefits promised in
the label to the consumer
 Pharmaceutical Quality = f (Properties of Drug Substance,
excipients, Mfg. Process,
Packaging)

23. WHAT IS PHARMACEUTICAL QBD ?
 It is a systematic approach to pharmaceutical
development that begins with predefined objectives
and emphasizes product and process
understanding and process control, based on
sound science and quality risk management.

24. OVERVIEW OF QBD
Labeled Use
Safety & Efficacy
Design Formulation
Design Process
Identify
Critical Material
Attributes (CMA) &
Critical Process
Parameters (CPP)
Define
Target Product Quality
Profile (TPQP)
Knowledge Space
Establish
Control Strategy
Monitor &
Update
Process
Target --------------------------- Design ----------------------- Implementation

25. KEY COMPONENTS OF QBD
Target Product Profile (TPP)
 It is patient & labeling centered concept
 It includes
 Route of administration
 Dosage form and size
 Max. & Min. Doses
 Pharmaceutical elegance (appearance)
 Target patient population

26. KEY COMPONENTS OF QBD
Target Product Quality Profile (TPQP)
 It is quantitative surrogate for aspects of
clinical safety & efficacy
 It includes quantitative targets for
 Impurities & stability
 Dissolution release profile &
 Other product specific performance requirements
e.g.
 Bioequivalence to the RLD for generic products
 Resuspendability for an oral suspension
 Adhesion for a transdermal system
 Viscosity for a topical cream etc.

27. KEY COMPONENTS OF QBD
Critical Quality Attributes (CQAs)
 These are Physical, chemical, biological or
microbiological properties or characteristics of final
product that need to be controlled (directly or
indirectly) to ensure product quality e.g. Dissolution
test
 CQAs include both
 Aspects of product performance
 Determinants of product performance

28. KEY COMPONENTS OF QBD
Critical Material Attributes (CMAs)
 These are Physical, chemical, biological or
microbiological properties or characteristics
of raw materials & mfg. process parameters
that need to be controlled to ensure product
quality
 These are independent of each other e.g.
Particle Size & Hardness areCMAs
CQA of RM & Mfg. Process Parameters =
CMA

29. KEY COMPONENTS OF QBD
Process Parameters (PP)
 It is any input operating parameter (mixing speed,
flow rate) and
process state variable (temperature, pressure) of a
process or unit operation
 Classification of PP for a Unit Operation
 Unclassified Process Parameters (UPP)
 Critical Process Parameters (CPP)
 Non-critical Parameters (non-CPP)

30. CLASSIFICATION OF
PROCESS PARAMETERS
Parameter
Type
Definition Sensitivity
non-CPP Not critical • No failure in target product quality profile
(TPQP) observed or predicted in the potential
operating space (POS), and
• No interactions with other parameters in the
proven acceptable range (PAR)
UPP Criticality
Unknown
• Not established
• The default in the absence of pharmaceutical
Development
CPP Critical
(control needed
to ensure
quality)
• Failure in target product quality profile (TPQP)
observed or predicted in the potential operating
space (POS), or
• Interactions with other parameters in the proven
acceptable range (PAR)

31. IDENTIFICATION OF
PROCESS PARAMETERS
Wet
Granulation
Material Attributes
Drug Substance
DS Amount
DS Form
DS Particle Size
DS Moisture Content
DS Bulk Density
Material Attributes
Excipients
Exp. Amount
Exp. Particle Size
Exp. Bulk Density
Granulation
Operating Parameters
Chopper Configuration
Impeller Speed
Granulation Time
Order of Addition
Temperature
Spray Nozzle Type
Binder Addition Rate
Granulation
State Conditions
Power Consumption
Temperature
Material Attributes
After Granulation
Blend Uniformity
Granule Size Distribution
Agglomerate Size
Moisture
Bulk Density
Flow Properties

32. KEY COMPONENTS OF QBD
Design Space
 The multidimensional combination and interaction
of input variables (e.g., material attributes) and
process parameters that have been demonstrated
to provide assurance of quality
 A design space may be constructed for a single unit
operation, multiple unit operations, or for the entire
process

33. TOOLS TO IMPLEMENT QBD
 Design of experiments (DOE)
 Risk assessment
 Process analytical technology (PAT)

34. DESIGN OF EXPERIMENT (DOE)
 Structured, organized method for
determining the relationship between
factors affecting a process and the
response of that process
 DOE Methodology
1. Choose Experimental Design (e.g. Full
Factorial design)
2. Conduct randomized experiments
3. Analyze data
4. Create multidimensional surface model

35. RISK ASSESSMENT
 Risk
 It is defined as the combination of the probability
of occurrence of harm and the severity of that
harm
 Risk assessment
 A systematic process of organizing information to
support a risk decision to be made within a risk
mgmt process.
 It consists of the identification of hazards and the
analysis and evaluation of risks associated with
exposure to those hazards

36. PROCESS ANALYTICAL TECHNOLOGY
(PAT)
A system for designing, analyzing and
controlling manufacturing through timely
measurements (i.e. during processing) of
critical quality and performance attributes of
raw & in process materials and processes
with the goal of ensuring final product
quality.
 The term analytical in PAT is viewed broadly
to include chemical, physical,
microbiological, mathematical and risk
analysis conducted in an integrated manner.

37. CONCLUSION
The End

38. CONCLUSION
Quality by design is an essential part of the
modern approach to pharmaceutical quality
QbD is Win-Win
PAT, DOE and Risk Assessments are tools
to facilitate the implementation of QbD.

39. THANK YOU!
Dr. Saurabh Arora
Presentation will be available for download @
WWW.Lab-Training.Com