M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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Pharmaceutical Development
Mohamad Haitham Ayad
2008
ICH Q8 Annex
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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REGULATORY STATUS : STEP 3
TRANSMISSION TO CHMP November 2007
TRANSMISSION TO INTERESTED PARTIES
November 2007
DEADLINE FOR COMMENTS May 2008
FINAL APPROVAL BY CHMP ?
DATE FOR COMING INTO OPERATION
?
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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WHY
ICH Q8 ANNEX
?
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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THE WALL STREET JOURNALSeptembre 3, 2003
Pharmaceutical manufacturing techniques lag behind those of potato-
chip and laundry soap makers
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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APPROACHES TO PHARMACEUTICAL DEVELOPMENT (1)
MINIMAL APPROACH :- Empirical development often conducted
one variable at a time- Fixed manufacturing process- Off-line analysis- Drug product quality controlled by
intermediate and end product testing- Reactive life cycle management
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APPROACHES TO PHARMACEUTICAL DEVELOPMENT (2)
ENHANCED, QUALITY BY DESIGN APPROACH (QbD) :
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.
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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APPROACHES TO PHARMACEUTICAL DEVELOPMENT (3)
QUALITY BY DESIGN APPROACH (QbD) : - Multivariate expeiments to understand product
and process- Adjustable manufacturing process within design
space- PAT Tools- Drug product quality ensured by risk-based
control strategy- Continual improvement live cycle management
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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ADVANTEGES OF QUALITY BY DESIGN APPROACH
Higher level of assurance of product quality Cost saving and efficiency for industry and
regulators Increase efficiency of manufacturing process and
reduce manufacturing cost and product rejects Minimize/eliminate potential compliance actions,
costly penalties and recalls Enhance opportunities for first cycle approval Streamline post approval manufacturing changes and
regulatory processes Opportunities for continual improvement
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (1)
1) TARGET PRODUCT PROFILE Dosage form and route of administration Dosage form strength Therapeutic moiety realise and
pharmacokinetic characteristics (ex : dissolution profil)
Drug product quality criteria (ex : sterility, purity)
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (2)2) CRITICAL QUALITY ATTRIBUTES (CQA) Physical, chemical, biological, or
microbiological property that should be within an appropriate limit to ensure the product quality.
Potenial CQA can be identified from target product profile and prior knowledge.
CQAs are used to guide product development.
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (3)
3) LINKING MATERIAL AND PROCESS ATTRIBUTE TO CQA BY USING RISK ASSESSMENT
Risk assessment tools can be used to identify and rank parameters with potential to have impact on product quality.
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (4)
Manufacturing Implementation
Process Scale-up & Tech Transfer
Risk Management
Process Development
FormulationDevelopment
Product qualitycontrol strategy
RiskControl
RiskAssessment
Process design space
ProcessUnderstanding
Excipient & drug substance design space
Product/prior Knowledge
RiskAssessment
Continualimprovement
ProcessHistory
RiskReview
Role of Quality Risk Management
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (5)
4) DESIGN SPACE
linking the process inputs and CQA to establish the appropriate process parameters
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (6)
Design SpaceControlSpace
Internal TargetSpecification
Continuous improvementwithout regulatory
approval Design Space
Knowledge Space
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (7)
Response surface plot of dissolutionas a function of two parameters of a granulationoperation. Dissolution above 80% is desired.
Example Of Presentation Of Design Space
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (7)
Response surface plot of dissolutionas a function of two parameters of a granulationoperation. Dissolution above 80% is desired.
Example Of Presentation Of Design Space
M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (8)
5) CONTROL STRATEGY A control strategy is designed to
consistently ensure product quality.
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (9)
ELEMENTS OF A CONTROL STRATEGY CAN INCLUDE THE FOLLOWING:
• Control of input material attributes (e.g., drug substance, excipients, 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 drying on degradation, particle size distribution of the granulate on dissolution)
• 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.
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PHARMACEUTICAL DEVELOPMENT STEPS ACCORDING TO QbD (10)
6) PRODUCT LIFECYCLE MANAGEMENT
AND CONTINUAL IMPROVEMENT
A design space provides the applicant flexibility to optimize and adjust a process as managed under their quality system