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
gregg.claycamp@fda.hhs.gov

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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 Analysis

Risk Management Tools

Risk Evaluation
Risk Communication

unacceptable

Risk Control

Risk Reduction

Risk Acceptance

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
Process-
step
Risk
Decision identification

Feedback
procedure
Risk
Sub-Sub- Sub- analysis
process process

Start
Start

Etc.

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
Design management

Process

Materials Manufacturing

Facilities
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 What is the chance

Design parameters and (probability) of “falling
their intersection in a
“design space” concept
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 Company Shareholder

Patient Harm
Advantage Viability Harm

ICH Q9 Impact

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Quality Risk Management

Severity and Probability  Risk

Increasing Probability of
Occurrence

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:

• 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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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

Y
ONL
E
A BL
T
LE Probability of Occurrence
A MP
S Health
Very Very
Severity Scale Low Low Medium High High
Death Medium Medium High High High
A
Hospitalization Low B
Medium High Risk
Medium High High

Medium
Acute Illness Low Medium Medium High High
Risk
Low
Worry Low
Risk Low Low C Medium Medium

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Quality Risk Management

Risk Ranking –High Level

Facility (Risk Ranking)

Scored and Prioritized
Process Under Multiple Criteria
1. Site M
2. Site T
3. Site C
Product 4. Site D
5. Site X
ART 6. Site A
C H
PLE
M
SA

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Quality Risk Management

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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 Quality Risk Management

FME(C)A

SxO Criticality
10 10
9 Occurrence Probability 9
1
Severity of Effect

8 8
2
7 7 3
6 6 “SOD” or
S O 4 SxOxD
“Risk
5 5 5 Number”
4 4 6
Detection* 7
3 3
8
2 2 9
1 1 10
*Higher detection ability
lowers risk score.
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Quality Risk Management

FME(C)A—Intermediate Tool

R T
A
CH
LE
P
M
SA
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Quality Risk Management

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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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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