presentation ich q8 annex qbd- november 2008

M. H. AYAD novembre 2008 Pharmaceutical Development : Q8 and annex

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Pharmaceutical Development

Mohamad Haitham Ayad

2008

ICH Q8 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

?


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WHY

ICH Q8 ANNEX

?


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THE WALL STREET JOURNALSeptembre 3, 2003

Pharmaceutical manufacturing techniques lag behind those of potato-

chip and laundry soap makers


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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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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.


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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


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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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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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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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4) DESIGN SPACE

linking the process inputs and CQA to establish the appropriate process parameters


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Design SpaceControlSpace

Internal TargetSpecification

Continuous improvementwithout regulatory

approval Design Space

Knowledge Space


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Response surface plot of dissolutionas a function of two parameters of a granulationoperation. Dissolution above 80% is desired.

Example Of Presentation Of Design Space


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Response surface plot of dissolutionas a function of two parameters of a granulationoperation. Dissolution above 80% is desired.

Example Of Presentation Of Design Space


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5) CONTROL STRATEGY A control strategy is designed to

consistently ensure product quality.


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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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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

presentation ich q8 annex qbd- november 2008

Health & Medicine