1 ich q9: quality risk management h. gregg claycamp, ph.d. office of new animal drug evaluation...
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ICH Q9: Quality Risk Management
H. Gregg Claycamp, Ph.D.Office of New Animal Drug Evaluation
CDER ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE (ACPS)
October 5-6, 2006 Rockville, MD
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Quality Risk Management
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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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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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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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Q9’s Sample Process
Risk Review
Risk Assessment
Risk Evaluationunacceptable
Risk Control
Risk Analysis
Risk Reduction
Risk Identification
Review Events
Risk Acceptance
InitiateQuality Risk Management Process
Output / Result of theQuality Risk Management Process
Ris
k M
an
ag
em
en
t To
olsR
isk
Co
mm
un
ica
tio
n
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QRM is not a Single ProcessStart
End
Risk identification
Risk analysis
Etc.
Process-step
Decision
Feedback procedure
Start
End
Start
End
Sub-process
Sub-Sub-process
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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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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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Concept: Link Back to Patient Risk
Process
Materials
Design
Manufacturing
Distribution
Patient
Facilities
Opportunities to impact risk using quality risk
management
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QRM and the Design Space
What is the chance (probability) of “falling outside” of the design space per unit time?
Risk analysts estimate probabilities of being outside (or inside!) of design limits, given various scenarios.
Design parameters and their intersection in a “design space” concept
v1
v2
v3
design space
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“Systems” thinking and methods!
A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecyle.
QRM: Another Systems Approach
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“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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Severity and Probability Risk
Increasing Severity of Harm/Consequence
Incr
easi
ng P
roba
bilit
y of
O
ccur
renc
e
Low Risk
Medium Risk
High Risk
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Tools for Risk Management
ICH Q9 Includes an Annex of Tools
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“High-Level” Tools
Often rely mixed kinds of information:• Quantitative
• Qualitative
• Expert judgment
Focus on systematic thinking:• Define the risk question
• Organize information under categories, attributes
• Build decision making paths
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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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Qualitative Risk Estimation
Health
Severity Scale
Probability of Occurrence
Very Low Low Medium High
Very High
Death Medium Medium High High High
Hospitalization Low Medium Medium High High
Acute Illness Low Medium Medium High High
Worry Low Low Low Medium Medium
SAMPLE TABLE ONLY
Low Risk
Medium Risk
High RiskA
B
C
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Risk Ranking –High Level
Process
Facility
Product
1. Site M
2. Site T
3. Site C
4. Site D
5. Site X
6. Site A
Scored and Prioritized Under Multiple Criteria
(Risk Ranking)
SAMPLE CHART
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Mid-Level: Combinations of Methods
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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FME(C)A
10987654321
Sev
erity
of
Eff
ect
10987654321O
ccur
renc
e P
roba
bilit
y
S
CriticalityS x O
123456789
10Det
ectio
n*
“SOD” or “Risk
Number”
O S x O x D
*Higher detection ability lowers risk score.
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FME(C)A—Intermediate Tool
SAMPLE CHART
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Present Status of the Guideline
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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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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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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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.”