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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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Examplain – Risk management

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Examplain – Risk management

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Examplain

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Examplain – Process control

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Examplain – Design Space

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Examplain – Control Strategy

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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)