2.7 a risk-based approach to pharmaceutical development
TRANSCRIPT
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A risk-based approach to pharmaceutical
development
ICH Q8/Q9/Q10
Oslo, January 29 2009
Øyvind Holte
Norwegian Medicines Agency
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Q8Q9
Q10
PAT
Formal Experimental Design
Real-Time
ReleaseMultivariate
Data Analysis
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Formulation
development
ICH Q8, Q9, Q10 and Pharmaceutical Development
Product life cycle
KnowledgeActive ingredient
Formulation
Manufacturing process
development
Routine
manufacture
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ICH Q8, Q9 and Pharmaceutical Development
• Fundamental concept of ICH Q8, Q9:
• Product quality should be built in by design
• Enhanced approach versus minimal approach
to pharmaceutical development
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ICH Q8, Q9 and Pharmaceutical Development
• Enhanced approach to pharmaceutical
development
• Thorough knowledge of the formulation/ product and
the manufacturing process
• Risk- and science-based development of the
formulation and the manufacturing process
• Establishment of a Design space
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ICH Q8, Q9 and Pharmaceutical Development
• Enhanced approach to pharmaceutical
development - Post-approval flexibility
• Routine manufacture• Monitoring of the process and critical intermediates
• Non-destructive real-time analysis
• Feed-back or feed-forward controls
• Flexible manufacturing process
• Changes within design space
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ICH Q8, Q9 and Pharmaceutical Development
ICH Q8
• Minimal versus enhanced
approach to Pharmaceutical
development
• Design space and interaction
effects between process
parameters
• Control strategies, including
real-time release
• Definition of key concepts
ICH Q9
• Principles of quality risk
management
• Quality risk management
process
• Risk management tools/
methodology
• Definition of key
concepts
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ICH Q9: Risk
management
• Continuous
process
spanning the
entire product
life cycle
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Process Analytical Technology: A brief overview
Enhanced approach
to pharmaceutical
development
Built-in
quality by
design
Process Analytical
Technology
Fast
Non-destructive
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Process Analytical Technology: A brief overview
Pérez-Ramos et al. AAPS PharmSciTech 6(1) 2005
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Process Analytical Technology
ICH Q8: ”PAT: A system for designing and
controlling manufacturing through timely
measurements (i.e. during processing) of critical
quality and performance attributes for raw and in-
process materials and also processes with the
goal of ensuring final product quality”
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Process Analytical Technology
Enhanced product quality control
Experimental
design
New analytical
tools (PAT)+
A deeper understanding of the product and the manufacturing process
+Risk
management
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ICH Q8, Q9, Q10 and batch release
Examplain: Pharm.Tech Europe 18(12) (2006)
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Real-time release
• The product specification still applies as for
traditionally released products
• Conformance to the specification is
demonstrated in a different way: Not by end
control, but by prediction from information
elements obtained during manufacture
• During shelf life, traditional testing applies
• Selected tests may be substituted one by one,
resulting in a reduced end control scheme
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Summary and Conclusion
Built in quality by design
• Risk management
• Enhanced pharmaceutical
development
• PAT tools
Product life cycle
• Development
• Technology transfer
• Manufacturing
• Discontinuation
References
• EMEA home page: PAT Q&A, EMEA PAT team
http://www.emea.europa.eu/Inspections/PAThome.html
• FDA: PAT – a framwork for innovative pharmaceutical development, manufacturing
and quality assurance (2004)
http://www.fda.gov/cder/guidance/6419fnl.pdf
• Examplain: Pharm.Tech Europe 18(12) (2006)