ICH Guideline Q8 Pharmaceutical Development

1. Presented By
Bindiya Patel
M.PHARM
(PHARMACEUTICS)

2. Aim
Objective
Introduction
System Before Q8
QbD
ICH Q8 Material Attributes
ICH Q8 Formulation
Contents For 3.2.P.2
Formulation Development Activities
Commercial Manufacturing Activities
Q8 Annexure
Future State Vision
Conclusion
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3.  To review and study ICH guidelines Q8
 To understand the concept of ICH guidelines Q8
 To know the importance and study the benefits of
ICH guidelines Q8
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4. High level purpose of Q8 is –
1. To provide [harmonised] guidance on the contents of
section 3.2.P.2 (pharmaceutical development) for new drug
products.
2. An opportunity to present the knowledge gained through
the application of scientific approaches to product and
process development (= scientific understanding) .
3. Consult with the appropriate regulatory authorities.
4. Adoption of Q8 philosophies can create a new paradigm
and set of opportunities for Industry and Regulators.
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5. Describes good practices for pharmaceutical
product development
„Introduces concepts of
1. „Design space „
2. Flexible regulatory approaches „
3. Quality Risk Management (Q9) „
Does not discuss QbD
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6. 1. Product quality and performance achieved and assured by
design of effective and efficient manufacturing
processes.
2. Product specifications based on mechanistic
understanding of how formulation and process factors
impact product performance.
3. An ability to effect Continuous Improvement and
Continuous "real time" assurance of quality.
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7.  Create a basis of flexible regulatory approaches by
reducing uncertainty.
1. Facilitate risk based regulatory decisions.
2. Continuous improvements without the need for
regulatory review.
3. ”Real time” quality assurance.
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8. 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.
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.
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9. 9
Variable X
Variable Y
Traditional process – limited knowledge – 3 batches, any
change needs new data and new approval
New paradigm: influence
of factors explored
creating knowledge. Risk
analysis of impact of
change is possible.
Approval to move within
defined area post-
approval could give
flexibility for
continuous improvement
without need for
further approval

10. Higher level of assurance of product quality
„Cost saving and efficiency for industry
1. Increase efficiency of manufacturing process
„2. Minimize/eliminate potential compliance actions
3. „Provide opportunities for continual improvement
4. Facilitate innovation „
More efficient regulatory oversight
1. „Enhance opportunities for first cycle approval.
„2. Streamline post approval manufacturing changes and
regulatory processes. 10

11. Drug substance
–physicochemical and biological properties in relation to
product performance and manufacturability
Excipients
- concentration, characteristics and functionality in
relation to product performance and manufacturability
- functionality during shelf-life
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12. Summary describing
1. Pharmaceutical development from initial concept to
final design.
2. Identification of attributes and interacting variables
critical for product quality i.E. Drug substance,
excipients (ranges), container closure system, dosing
device (if relevant), manufacturing process.
3. Formulations from pivotal clinical safety/efficacy
studies.
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13. Part 1
Core document
Baseline expectations
Optional information
Regulatory Flexibility
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Revision
Annexes relating to
specific dosage forms
(as Q6a)
References to use of
risk management
Focus on guiding towards
Desired State
Step 4: Nov 2005 Drafting underway

14. 14
Product
development
Technology
transfer
Commercial
manufacture
Demonstration of
greater under-
standing of
pharmaceutical and
manufacturing
sciences can create
a basis for flexible
regulatory
approaches.
Design quality
product &
process to
consistently
deliver intended
performance.
Manufacturing
process
improvements,
within the
approved design
space, without
further
regulatory
review.

15.  3.2.P.2.1 Components of drug product (drug
substance/ excipients)
 3.2.P.2.2 Formulation Dev.
 3.2.P.2.3 Manufacturing Process Development
 3.2.P.2.4 Container Closure System
 3.2.P.2.5 Microbiological Attributes
 3.2.P.2.6 Compatibility
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16. Activities ICH Q8(R2) – Pharmaceutical
Development
Related Activities
Process Screening • Exploration of unit operations
• Characterization of process
intermediates
Process Development and
Optimization
(Lab Scale)
• DOEs for process parameters and
interactions with material
attributes
• Development of Design Space
• understanding of critical process
operations
Process Development and
Optimization
(Pilot Scale)
• DOEs for process parameters and
interactions with material
attributes
• Development of Design Space
• understanding of critical process 16

17. Activity ICH Q8(R2) – Pharmaceutical
Development
Related Activities
Technology Transfer • Gain product and process knowledge
• Knowledge supports transfer between
development and manufacturing to
achieve product realization
Commercial Scale
Manufacturing for Drug
Product
• Definition of commercial process design
• Commercial scale runs to verify process
design, with additional sampling to verify
understanding
• Implementation of on-line measurement
technologies
Continual Process
Verification and Continual
Improvement
• On-going analysis and trending of
process data, (multivariate SPC, etc.)
• Evaluation of process changes and 17

18. Define Target Product Profile
Identify ‘CQAs’ – Critical Quality Attributes of Product
Determine QAs of inputs – materials/parameters etc.
Select appropriate process
Determine functional relationships between material
attributes & process parameters to Product CQAs
Identify a control strategy
Propose a “design space”
Define and describe design space in regulatory submission
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19. REGULATORS INDUSTRY
1. Promote open communication
2. Reviewers who are
accessible, engaged, and
expert
3. Change the content of
applications Encourage
knowledge sharing Eliminate
non-value added information
4. More science & risk-based
evaluation of applications
5. Reduce post-approval
change regulatory hurdles
1. Be open and transparent in
sharing knowledge: success and
failure.
2. Scientists can understand the
needs of the Regulators.
3. Change the content of
applications.
-Share the knowledge.
-Focus on manufacturing sciences.
1. Move to science-based, risk
mitigated applications
2. Provide insight into manufacturing
sciences so as to reduce need for
post-approval change 19

20. ExistingExisting GMPGMP’’ss
Quality by Design
(Pharmaceutical
Development)
Quality Risk
Management
The Regulatory
Quality System
Our vision: The future Pharmaceutical Quality System
Quality
Systems
Quality
Systems
(Q10)
For companies with :
1. Good design and
control strategies
2. Good Risk
Management strategies
3. Good Quality Systems
Quality Risk
Management
(Q9)
Quality
by Design
(Q8)
Reduced regulatory
burden:
• Reduction of
submissions on
changes/variations
• Inspection of quality
systems
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21. Agencies and Industry are moving from ‘blind’ compliance to
‘science and risk-based’ compliance Industry wants this to be
global.
This evolution is based on process understanding and continuous
improvement throughout the product life cycle Traditional process
validation being replaced by a much better alternative.
- Building in quality.
- Continuous quality verification and improvement.
Moving from ‘Quality by Testing’ to ‘Quality by Design’ should, in
principle, allow significant regulatory flexibility helps both
regulators and industry focus on higher risk or added value
activities.
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