1. 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

2. 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

3. 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)

4. 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

5. Q9’s Sample Process Risk Communication Risk Management Tools Initiate
Risk Review
Risk Assessment
Risk Evaluation
unacceptable
Risk Control
Risk Analysis
Risk Reduction
Risk Identification
Review Events
Risk Acceptance
Initiate
Quality Risk Management Process
Output / Result of the
Risk Communication
Risk Management Tools

6. QRM is not a Single Process
Start
Process- step
Risk identification
Decision
Feedback procedure
Risk analysis
Sub-Sub- process
Sub- process
Start
End
Start
End
Etc.
End

7. 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.

8. 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.”

9. Concept: Link Back to Patient Risk
Opportunities to impact risk using quality risk management
Design
Process
Materials
Manufacturing
Facilities
Distribution
Patient

10. 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
What is the chance (probability) of “falling outside” of the design space per unit time?
Design parameters and their intersection in a “design space” concept

11. 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!

12. “Risk Management” is Universal
Company
Strategic Risks
Operational Risks
Financial Risks
Compliance Risks
Competitor Advantage
Company Viability
Shareholder Harm
Patient Harm
ICH Q9 Impact

13. Severity and Probability  Risk
High Risk
Increasing Probability of Occurrence
Medium Risk
Low Risk
Increasing Severity of Harm/Consequence

14. Tools for Risk Management
ICH Q9 Includes an Annex of Tools

15. “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

16. Examples of implementation: FDA
CDER/ORA Site Selection process for GMP inspections
CVM pre-approval decision support system (PAIDSS)
Other efforts in progress

17. Qualitative Risk Estimation
SAMPLE TABLE ONLY
Health
Severity Scale
Probability of Occurrence
Very Low
Low
Medium
High
Very High
Death
Hospitalization
Acute Illness
Worry
Low Risk
Medium Risk
High Risk A B C

18. Risk Ranking –High Level
Facility
(Risk Ranking)
Site M
Site T
Site C
Site D
Site X
Site A
Scored and Prioritized Under Multiple Criteria
Process
Product
SAMPLE CHART

19. 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

20. FME(C)A 10 9 8 7 6 5 4 3 2 1 10 9 8 7 6 5 4 3 2 1 Severity of Effect
Criticality
S x O 10 9 8 7 6 5 4 3 2 1 10 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8 9 10
“SOD” or “Risk Number”
S x O x D
Severity of Effect S O
Occurrence Probability
Detection*
*Higher detection ability lowers risk score.

21. FME(C)A—Intermediate Tool
SAMPLE CHART

22. Present Status of the Guideline
Published as US Guidance, June 2006
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:

23. 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?

24. 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

25. 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.”