Presentation on Quality by Design ‘Pharmaceutical GMPs for the 21st Century’ By: Akhilesh Kumar Dwivedi Dr. Reddy’s Labs. F.T.O-III Date: 18 Jan 2011 QUALITY BY DESIGN
Presentation on Quality by Design
‘Pharmaceutical GMPs
for the 21st Century’
By: Akhilesh Kumar Dwivedi
Dr. Reddy’s Labs. F.T.O-III
Date: 18 Jan 2011
QUALITY BY DESIGN
QUALITY BY DESIGN
processes products
HISTORY: Quality by Design (QbD) is a concept first outlined by well-known quality expert Joseph M. Juran in various publications, most notably Juran on Quality by Design. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned in the first place.
QUALITY BY DESIGN
What is Quality?
Requirements= need or expectations
Quality
Patient(or surrogate)
Target ProductQuality Profile
“Good pharmaceutical quality represents an acceptably low risk of failing to achieve
the desired clinical attributes.”
The quality mantra
“Quality can not be tested into
products; it has to be built in
by design”
“Quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skillful execution; it represents the wise choice of many alternatives.”
How can we modernize our industry?
More knowledge of our products and processes, allowing better design and more control
Better management:- introduction of quality risk management- expansion of GMP to more extensive pharmaceutical quality system
The knowledge pyramid
CORRELATIVE KNOWLEDGEWhat Is Correlated to What?
“CAUSAL" KNOWLEDGEWhat “Causes” What?
MECHANISTICKNOWLEDGE
How?
DESCRIPTIVE KNOWLEDGE: What?
Need
for
reg
ula
tory
overs
igh
t
Kn
ow
led
ge b
ase
d d
ecisio
ns
Desired State
Current State
FirstPrinciples Why?
The New Quality Paradigm – The Evolving Regulatory Framework
ICH Q8/Q8(R) - Pharmaceutical Development
PAT Guidance
ICH Q9 – Quality Risk Management
ICH Q10 – Pharmaceutical Quality Systems
ProductDesign
Process Design
Scale-up &Transfer
Commercial Manufacture
Product Life Cycle
Product
Definition: Quality by Design
Quality by Design 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.
Quality by Design approach can be used for
• Simple dosage forms
• Advanced drug delivery systems
• Devices
• Combination products
• Active pharmaceutical ingredients
• Materials incl excipients
• Analytics
• Companies re-organize their science
• Universities change their curriculum
• Health authorities change their assessment and inspection
Impact of QbD
QUALITY BY DESIGN
Step 1. Agree on the Target Product Profile
Step 2. Determine the Critical Quality Attributes (CQAs)
Step 3. Link the drug and excipient attributes and the
process parameters to the CQAs
Step 4. Define the Design Space
Step 5. Define the Control Strategy
Step 6. Prepare QbD registration file
Step 7. Product lifecycle management and
continual improvement
What are the steps in aQuality by Design approach?
What are the steps in aQuality by Design approach?
1. TARGET PRODUCT PROFILE
2. CRITICAL QUALITY
ATTRIBUTES
6. PRODUCT LIFECYCLE
MNGMNT
3. LINK MAs AND PPs
TO CQAS
5. ESTABLISHCONTROL STRATEGY
4. ESTABLISHDESIGN SPACE
Step 1. Agree on the Target Product
ProfileTarget Product Profile: - a prospective and dynamic summary of the quality characteristics of a drug product - that ideally will be achieved to ensure that the desired quality, and hence the safety and efficacy, of a drug product is realized.
The TPP forms the basis of design of the product.
Consider: dosage form route of administration strength release / delivery of
the drug pharmacokinetic
characteristics (e.g., dissolution; aerodynamic performance)
drug product quality criteria (e.g., sterility, purity).
CRITICAL QUALITY ATTRIBUTES - definition
CRITICAL QUALITY ATTRIBUTES - definition
A critical quality attribute (CQA) is 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.
Step 4. Define the Design SpaceStep 4. Define the Design Space
The linkage between - the process inputs (input variables and process parameters) and - the critical quality attributes
can be described in the design space.
Definition of Design SpaceDefinition of Design Space
The material attributes and process parameters that assure quality.
The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have beendemonstrated to provide assurance of quality.
Roll
pre
ssure
Gap width
Screen Size
Step 5. Define the Control StrategyStep 5. Define the Control Strategy
The control strategy should describe and justify how
in-process controls and
the controls of - input materials (drug substance and excipients), - container closure system, - intermediates and
the controls of end products
contribute to the final product quality
5. CONTROL STRATEGY5. CONTROL STRATEGY
Elements of a control strategy can include, but are not limited to, the following:
• Control of input material attributes (e.g., drug substance, adhesive polymer, primary packaging materials) based on an understanding of their impact on processability or product quality
• Product specification(s)
• Controls for unit operations that have an impact on downstream processing or end-product quality (e.g., the impact of solvent on degradation)
• In-process or real-time release in lieu of end-product testing
• A monitoring program (e.g., full product testing at regular intervals) for verifying multivariate prediction models.