II. 3 Quality risk management as part of

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II. 3 Quality risk management as part of
Industry

• Development

Competent Authorities
See also next chapters using the intention to be
applicable for development II.4 Facilities,
Equipment and Utilities II.5 Materials
Management II.6 Production II.7 Laboratory
Control and Stability Studies II.8 Packaging and
Labelling
Note Process understanding and criticality may
be applied only to new products
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About development
T. Matsumura, Eisai Co.
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II.3 QRM as part of development

• To design a quality product and its manufacturing
  process
• to consistently deliver the intended performance
  of the product (see ICH Q8)
• To enhance knowledge of product performance over
  a wide range of
• material attributes (e.g. particle size
  distribution, moisture content, flow properties)
• processing options
• process parameters

ICH Q9
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Quality by design Special Cause or Common
Cause
Note Non detected OoS could result in a patient
risk
Production
Validation

• Consequence Frequent, major OOS
• Corrective actions eliminate Special Cause
• Result Unstable process

Based on A. Hussain, FDA, September 2004
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Quality by design Special Cause or Common
Cause
Production
Validation

• Reduce Common Cause Variability
• Consequence On the continuous improvement path
• Result Stable Capable

A. Hussain, FDA, September 2004
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Quality by design Special Cause or Common
Cause
Production
Validation

• Consequence Minor, occasional OoS
• Reduce Common Cause Variability
• Result Stable- Yes Capable?

A. Hussain, FDA, September 2004
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II.3 QRM as part of development

• To assess the critical attributes of
• Raw materials
• Solvents
• Active Pharmaceutical Ingredient (API)
• Starting materials
• Excipients
• Packaging materials
• To establish appropriate specifications, identify
  critical process parameters and establish
  manufacturing controls

ICH Q9
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II.3 QRM as part of development

• To decrease variability of quality attributes
• reduce product and material defects
• reduce manufacturing defects
• To assess the need for additional studies (e.g.,
  bioequivalence, stability) relating to scale up
  and technology transfer
• To make use of the design space concept (see
  ICH Q8)

ICH Q9
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P2 of CTD as part of a regulatory submission
In line with Quality Risk Management ?
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P2 of CTD as Quality Risk Management process ?
Formulation Process design
Process understanding
Manufacturing Concept
Process control Concept
Product release Concept
Regulatory strategy
Review the submission
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Development
Target Product Profile
Drug substance properties prior knowledge
Developm.
Proposed formulation and manufacturing process
Determination of Cause Effect relationships
(Risk Identification with subsequent Risk
Analysis)
Risk-based classification (Risk Evaluation)
Process understanding
Re-evaluation and confirmation
Re-evaluation and confirmation
Formulation understanding
Parameters to investigate (e.g. by DOE)(Risk
Reduction 1. proposal 2. verified)
Product and process characteristics on the final
drug product
CONTROL STRATEGY
Operation
EFPIA PAT TG, 2006
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Risk Management approach to focus on critical
attributes
Significant influence
Initialassessment
Prior knowledge
First Second review cycle
Formulation and Process understanding
Thirdreview cycle
ControlStrategy
EFPIA PAT TG, 2006
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Risk to patient
Unit operation
Quality Attributes
EFPIA PAT TG, 2006
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Responsibilities in regulatory operations
Industry
B) Inspectorates
A) Reviewers
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QRM as part of developmentprovide risk-based
knowledge to manufacturer

• Past Future
• Parameters and range We have additional
  dimensions
• Open question How to challenge information for
  submission?
• Answer the questions in ICH Q9 Chapter 4
• What might go wrong?
• What is the likelihood (probability) it will go
  wrong?
• What are the consequences (severity)?

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Development and Manufacturing
Validation
Takayoshi Matsumura, Eisai