ich guideline q8 pharmaceutical development
DESCRIPTION
ICH Guideline Q8 Pharmaceutical DevelopmentTRANSCRIPT
ICH GUIDELINE Q8 PHARMACEUTICAL
DEVELOPMENT
Guided byProf. S. K. Shrivastav
Presented By Bindiya Patel
M.PHARM (PHARMACEUTICS)
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Presentation Outline... 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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Objective
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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Introduction 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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Cont...
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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On July 20th 2004 you were told Q8 could deliver…
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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Cont...
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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QbD Definition (ICH Q8(R))
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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Design Space Facilitates Regulatory Flexibility
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
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Why QbD?
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.
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ICH Q8: Material attributes 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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ICH Q8: Formulation/Dosage form
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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Q8 is a 2 part guideline
Part 1Core document Baseline expectationsOptional informationRegulatory Flexibility
RevisionAnnexes relating to specific dosage forms (as Q6a)References to use of risk managementFocus on guiding towards Desired State
Step 4: Nov 2005 Drafting underway
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Q8 applies throughout product life-cycle
Productdevelopmen
t
Technology transfer
Commercialmanufacture
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.
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Contents for 3.2.P.2 of CTD Quality Module 3
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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Formulation Development Activities
Activities ICH Q8(R2) – Pharmaceutical DevelopmentRelated 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 operations
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Commercial Manufacturing Activities
Activity ICH Q8(R2) – Pharmaceutical DevelopmentRelated 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 associated effect on intermediates and products
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Q8 Annexure
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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Future State Vision: Both Regulators and Industry need to change
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.4. Move to science-based, risk
mitigated applications5. Provide insight into
manufacturing sciences so as to reduce need for post-approval change
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July 2003: An ICH vision
Existing Existing 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 strategies2. Good Risk
Management strategies3. 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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CONCLUSION
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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