Transcript ICH Q9 Principles and Challenges

ICH Q9: Quality Risk
Management
CDER ADVISORY COMMITTEE FOR PHARMACEUTICAL
SCIENCE (ACPS)
October 5-6, 2006 Rockville, MD
H. Gregg Claycamp, Ph.D.
Office of New Animal Drug Evaluation
[email protected]
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Quality Risk Management
Why was ICH Q9 needed?

To ensure a common understanding of
Quality Risk Management (QRM) by both
industry and regulators
• To facilitate moving to the “Desired State”
• To facilitate communication and transparency
• To move from ‘fire fighting’ to management of risk

ICH Q9 explains
• A common language and process
• Potential methodologies for QRM
• Where QRM can add value
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Quality Risk Management
What’s in Quality Risk Management?

Q9 has broad risk concepts and principles

Principles for implementation

Elements of Risk Assessment/Management
Processes

Does not discuss a single tool, but “The Right
Tool for the Job” approach

Risk Management Tools
•
•
•
High-level (Ideas and Concepts)
Mid-Level (Quantitative and Qualitative)
Low-Level (Real numbers and real time)
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Quality Risk Management
What’s not in ICH Q9 …

A “cookbook” for risk management

A specific prescription for your risk
management program

An exhaustive treatment of theory

An exhaustive list of methods and tools
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Quality Risk Management
Q9’s Sample Process
Initiate
Quality Risk Management Process
Risk Assessment
Risk Identification
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Risk Management Tools
Risk Communication
Risk Analysis
Output / Result of the
Quality Risk Management Process
Risk Review
Review Events
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Quality Risk Management
QRM is not a Single Process
Start
Processstep
Risk
identification
Decision
Feedback
procedure
Sub-Subprocess
Start
Risk
analysis
Subprocess
Start
Etc.
End
End
End
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Quality Risk Management
Different Meanings of “Risk”

Individual: Risk is a cognitive and emotional
response to expected loss.

Society: Risk is a societal expression of
expected harm tempered by expected benefits.

Organizations: Risk is a combination of the
probability of occurrence and severity of
selected harms.

Technical: Risk is usually based on the expected
value of the conditional probability of the event
occurring times the consequence of the event
given that it has occurred.
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Quality Risk Management
Q9 Overarching Principles

“The evaluation of the risk to quality should
be based on scientific knowledge and
ultimately link back to the protection of the
patient; and

The level of effort, formality, and
documentation of the quality risk
management process should be
commensurate with the level of risk.”
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Quality Risk Management
Concept: Link Back to Patient Risk
Opportunities to impact
risk using quality risk
management
Design
Process
Materials
Facilities
Manufacturing
Distribution
Patient
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Quality Risk Management
QRM and the Design Space
Risk analysts estimate probabilities of
being outside (or inside!) of design
limits, given various scenarios.
v2
design space
v1
v3
Design parameters and
their intersection in a
“design space” concept
What is the chance
(probability) of “falling
outside” of the design space
per unit time?
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Quality Risk Management
QRM: Another Systems Approach

A systematic process for the
assessment, control, communication and
review of risks to the quality of the drug
product across the product lifecyle.
“Systems” thinking
and methods!
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Quality Risk Management
“Risk Management” is Universal
Company
Strategic Risks
Operational Risks
Financial Risks
Compliance Risks
Competitor
Advantage
Company
Viability
Shareholder
Harm
Patient Harm
ICH Q9 Impact
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Quality Risk Management
Increasing Probability of
Occurrence
Severity and Probability  Risk
High Risk
Medium
Risk
Low
Risk
Increasing Severity of Harm/Consequence
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Quality Risk Management
Tools for Risk Management
ICH Q9 Includes
an Annex of Tools
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Quality Risk Management
“High-Level” Tools

Often rely mixed kinds of information:

Focus on systematic thinking:
• Quantitative
• Qualitative
• Expert judgment
• Define the risk question
• Organize information under categories,
•
attributes
Build decision making paths
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Quality Risk Management
Examples of implementation: FDA



CDER/ORA Site Selection process for
GMP inspections
CVM pre-approval decision support
system (PAIDSS)
Other efforts in progress
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Quality Risk Management
Qualitative Risk Estimation
Probability of Occurrence
Health
Severity Scale
Death
Very
Low
Low
Medium
High
Very
High
Medium
Medium
High
High
High
High Risk
Medium
High
High
A
Hospitalization
Low
Acute Illness
Low
Worry
Low
Low
Risk
B
Medium
Medium
Medium
Risk
Medium
Low
Low
High
C Medium
High
Medium
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Quality Risk Management
Risk Ranking –High Level
Facility
(Risk Ranking)
Scored and Prioritized
Under Multiple Criteria
Process
1. Site M
2. Site T
3. Site C
Product
4. Site D
5. Site X
6. Site A
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Quality Risk Management
Mid-Level: Combinations of Methods


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More formula-driven than High-level tools
and approaches
Expert-driven qualitative with some data
•
•
FME(C)A
Decision analytic methods
Limitations
•
•
•
Which experts?
Risk-analytical methods
Sorting value- and perception-driven
assessments with quantitative variables
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Quality Risk Management
S
10
9
8
7
6
5
4
3
2
1
Criticality
SxO
O
Detection*
10
9
8
7
6
5
4
3
2
1
Occurrence Probability
Severity of Effect
FME(C)A
1
2
3
4
5
6
7
8
9
10
SxOxD
“SOD” or
“Risk
Number”
*Higher detection ability
lowers risk score.
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Quality Risk Management
FME(C)A—Intermediate Tool
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Quality Risk Management
Present Status of the Guideline


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Published as US Guidance, June 2006
•
http://www.fda.gov/cder/guidance/7153fnl.htm
Judging by industry and regulatory
conferences, workshops, publications: interest
in Q9 remains high
Some members of the ICH EWG compiled
presentations for information. Now available
on ICH website:
•
http://www.ich.org/cache/compo/276-254-1.html
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Quality Risk Management
Next Steps?


From great ideas to practice—how?
Both industry and regulators want to
know
• Which risks firsts?
• Which tools are best?
• How will I know “good” from “bad” risk
•
management?
Do we need dept./divisions of risk managers?
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Quality Risk Management
Examples of Implementation: Industry

Many presentations at conferences
showing examples of:
• Failure modes and effects analysis (FMEAs)
• Multivariate models (QC/QA integration)
• Systems design, modeling and application are
readily adaptable to QRM approaches
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Quality Risk Management
Keys to Implementation

Key to implementation: the systems
approaches in Q8-Q9-Q10 leverage the
best parts of existing knowledge bases
and expertise for systematic control of
risks to pharmaceutical quality.
• Gregg’s Pareto principle for QRM:
“More than
80% of the expertise for a Quality Risk
Management program exists among the
domain --i.e., not risk-- experts.”
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