Transcript ICH Q9 Quality Risk Management

Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
II. 3 Quality risk management as part of…
Development
Industry
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
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 1
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
CONSIDERATIONS
About development
Critical
Parameters
that contribute
to variation in customer
requirements
Parameters that impact
customer requirements
All parameters and dimensions
that define a product
T. Matsumura, Eisai Co.
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 2
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
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
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 3
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
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
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
Based on A. Hussain, FDA, September 2004
July 2006, slide 4
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
Quality by design : “Special Cause” or “Common Cause”
Production
Validation
 Reduce “Common Cause” Variability
 Consequence: On the continuous improvement path
Result: Stable & Capable
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
A. Hussain, FDA, September 2004
July 2006, slide 5
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
Quality by design : “Special Cause” or “Common Cause”
Production
Validation
 Consequence: Minor, occasional OoS
 Reduce “Common Cause” Variability
Result: Stable- Yes; Capable?
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
A. Hussain, FDA, September 2004
July 2006, slide 6
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
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
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 7
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
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
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 8
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
P2 of CTD as part of a regulatory submission
In line with Quality Risk Management ?
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 9
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
P2 of CTD as Quality Risk Management process ?
Initiate
Quality Risk Management Process
Formulation & Process design
Risk Assessment
Risk Identification
Risk Analysis
Process understanding
Risk Evaluation
Product release Concept
Regulatory strategy
Risk Communication
Process control Concept
unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Risk Management tools
Manufacturing Concept
Output / Result of the
Quality Risk Management Process
Risk Review
Review the submission
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
Review Events
July 2006, slide 10
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
Drug substance properties; prior knowledge
Proposed formulation and manufacturing process
Research
Formulation understanding Operation
Re-evaluation and confirmation
Determination of
Cause – Effect relationships
(Risk Identification with subsequent Risk Analysis)
Phase 1
Risk-based classification
(Risk Evaluation)
Parameters to investigate (e.g. by DOE)
(Risk Reduction 1. proposal; 2. verified)
FORMULATION
DESIGN SPACE
Phase 2
Product and process
characteristics on the
final drug product
CONTROL
STRATEGY
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
PROCESS
DESIGN SPACE
BY UNIT OPERATION
Review events
Launch
Process understanding
Re-evaluation and confirmation
Developm.
Development
EXAMPLE
Target Product Profile
Phase 3
July 2006, slide 11
EFPIA PAT TG, 2006
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
Risk Management approach to focus on critical attributes
Quality Attributes
Unit operation
Dispensing
Granulation
Drying
Dissolution
Disintegration
Hardness
Assay
Content
Uniformity
Degradation
Stability
Appearance
Identification
Water
Microbiology
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
Blending
Tableting
Significant
influence
Initial
assessment
Prior
knowledge
First & Second
review cycle
Formulation
and Process
understanding
Third
review cycle
Control
Strategy
July 2006, slide 12
EFPIA PAT TG, 2006
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
low
Process understanding
Control Strategy
Risk to patient
Quality Attributes
Unit operation
Dispensing (Raw
Material Properties)
Dissolution
Particle size API
Disintegration
Particle size API
Hardness
Prior knowledge
Prior knowledge
Prior knowledge
Assay
Prior knowledge
Prior knowledge
Prior knowledge
Content uniformity
Prior knowledge
Degradation
Prior knowledge
Power
consumption
Water amount and
feed rate
Stability
Prior knowledge
Prior knowledge
Appearance
Prior knowledge
Prior knowledge
Not critical to
quality
Not critical to
quality
Control water
content
Not critical to
quality
Identification
NIR of raw material Prior knowledge
Water
Microbiology
1
1
Unit operations
/
Quality attributes
Prior knowledge
Specification of
starting material
Granulation
Drying
Power
Prior knowledge
consumption
water amount and
Prior knowledge
feed rate
Prior knowledge
Blending
(Magnesium
Stearate)
Not critical to
quality
Not critical to
quality
Not critical to
quality
Prior knowledge
Tableting
Not critical to
quality
Not critical to
quality
Not critical to
quality
Packaging
Prior knowledge
Prior knowledge
Prior knowledge
NIR measurement
Prior knowledge
Not critical to
quality
NIR measurement
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Not critical to
quality
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
Control water
content
Prior knowledge
Prior knowledge
Prior knowledge
Purified water
used
Prior knowledge
Prior knowledge
Prior knowledge
Prior knowledge
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 13
EFPIA PAT TG, 2006
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
Responsibilities in regulatory operations
Initiate
Quality Risk Management Process
Industry
Team focused
Risk Assessment
Risk Identification
Risk Analysis
Risk Evaluation
Internal consultation
Stakeholder involvement
Risk Communication
Risk Control
Risk Reduction
Risk Acceptance
Output / Result of the
Quality Risk Management Process
Risk Management tools
unacceptable
B) Inspectorates
A) Reviewers
Risk Review
Review Events
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 14
Annex II: Potential Applications
ICH Q9 QUALITY RISK MANAGEMENT
EXAMPLE
QRM as part of development
provide 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)?
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 15
Development and Manufacturing
EXAMPLE
Conventional approach: Testing after each step to minimize the
risk prior to the next step
Raw
Materials
Blending
Tabletting
Packaging
Validation
Raw
Materials
Blending
Tabletting
Packaging
PAT: Continuous or more frequent testing and control during each
step to minimize/control the risk prior to the next step
PAT: Process Analytical Technology
Takayoshi Matsumura, Eisai