Ich - q9 Quality Risk Management Ótimo

Content
ICH Q9 QUALITY RISK MANAGEMENT
Quality
Risk Management
ICH Q9
Content
Disclaimer: This presentation includes the authors views on quality risk management theory and practice.
The presentation does not represent official guidance or policy of authorities or industry.
prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
July 2006, slide 1
Content
Purpose of this part
To guide through the content of the ICH Q9 document

Provide some considerations, possible interpretations
and where appropriate examples
July 2006, slide 2
Content
ICH Q9: Quality Risk Management (QRM)

Document is available on the ICH Webpage
www.ich.org
July 2006, slide 3
Content
Table of contents
1. Introduction
2. Scope
3. Principles of Quality Risk Management
4. General Quality Risk Management Process
5. Risk Management Methodology
Annex I: Risk Management Methods and Tools
6. Integration of QRM process
into Industry and Regulatory operations
Annex II: Potential Applications for QRM
7. Definitions
8. References
July 2006, slide 4
Content
1. Introduction
Risk Management
Quality Risk Management
Quality Systems
Harm
Severity
Stakeholder
Product Life Cycle
GMP Compliance
July 2006, slide 5
Content
2. Scope
This guideline provides
principles & examples of tools
of quality risk management that can be applied to
different aspects of pharmaceutical quality.
These aspects include development, manufacturing,
distribution, and the inspection and submission/review
processes throughout the lifecycle
of drug substances, drug (medicinal) products,
biological and biotechnological products
ICH Q9
July 2006, slide 6
Content
CONSIDERATIONS
2. Scope
Drug substances,
Drug (medicinal) products,
Biological and biotechnological products
Including the selection and use of
> Raw materials
> Solvents
> Excipients
> Packaging and labelling materials
> Components
July 2006, slide 7
Content
3. Principles of Quality Risk Management

Two primary principles:
The evaluation of
the risk to quality
should be based on
scientific knowledge
and ultimately link
to the protection
of the patient
The level of effort,

formality and
documentation
of the quality risk
management process
should be commensurate
with the level of risk
ICH Q9
July 2006, slide 8
Content
Systematic processes
designed to
coordinate, facilitate and improve
science-based decision making
with respect to risk to quality
ICH Q9
July 2006, slide 9
Content
Initiate
Quality Risk Management Process
4. A General
Quality
Risk
Management
Process
Risk Assessment
Risk Identification
Risk Analysis
Team
approach
unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Risk Management tools
Risk Communication
Risk Evaluation
Output / Result of the

Risk Review
Review Events
ICH Q9
July 2006, slide 10
Content

Decision makers:
Person(s)
with competence and authority
to make a decision
Coordinating
quality risk management process
across various functions and departments
ICH
Supporting
the team approach
Q9prepared by some members of the ICH Q9 EWG for example only; not an official policy/guidance
Management
responsibility
Ensuring that
ongoing Quality Risk Management processes operate
July 2006, slide 11
Content
CONSIDERATIONS

Team approach
Usually, but not always, undertaken by interdisciplinary
teams from areas appropriate to the risk being
considered e.g.
>
>
>
>
>
>
>
>
>
Quality unit
Development
Engineering / Statistics
Regulatory affairs
Production operations
Business, Sales and Marketing
Legal
Medical / Clinical
& Individuals knowledgeable of the QRM processes
July 2006, slide 12
Content

When to initiate and plan a QRM Process
First define the question which should be answered
(e.g. a problem and/or risk question)
> including pertinent assumptions identifying
the potential for risk
Then assemble background information and/ or data

on the potential hazard, harm or human health impact
relevant to the risk
> Identify a leader and necessary resources
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Output / Result of the Quality

Risk Management Process
ICH Q9
> Specify a timeline, deliverables and

appropriate level of decision making
for the QRM process
Initiate Quality
Risk Assessment
Risk Review
Review Events
July 2006, slide 13
Content
CONSIDERATIONS
When to apply Quality Risk Management?

Should risks
be assessed?
Are there clear rules

for decision making?
e.g. regulations
No or
justification needed
1. What might go wrong?

2. What is the likelihood (probability)
it will go wrong?
3. What are the consequences (severity)?
Can you answer

the risk assessment
questions?
Yes
no RM
Risk assessment not required
Yes
informal RM
No
formal RM
Agree on a team
(small project)
(No flexibility)
Initiate Risk assessment
Select a Risk Management tool
(risk identification, analysis & evaluation)
(if appropriate e.g. see ICH Q9 Annex I)
Follow procedures
Run risk control
Carry out the

quality risk management process
(e.g. Standard Operating Procedures)
(select appropriate measures)
Document results,
decisions and actions
Document the steps
Based on K. Connelly, AstraZeneca, 2005

July 2006, slide 14
Content

Risk Assessment
Risk Identification
What might go wrong?
3 fundamental
questions
Risk Analysis
What is the likelihood (probability) it will go wrong?
Risk Evaluation
What are the consequences (severity)?
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Note: People often use terms

Risk analysis, Risk assessment and
Risk management interchangeably
which is incorrect!
Risk Review
Review Events
July 2006, slide 15
Content

Risk Assessment: Risk Identification
What might go wrong?
A systematic use of information
to identify hazards
referring to the risk question or problem
> historical data
> theoretical analysis
Initiate Quality
Risk Assessment
> informed opinions
Risk Identification
Risk Analysis
Risk Communication
> concerns of stakeholders
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 16
Content

Risk Assessment: Risk Analysis
What is the likelihood it will go wrong?
The estimation of the risk
associated with the identified hazards.
A qualitative or quantitative process of linking
the likelihood of occurrence and severity of
harm
Initiate Quality
Risk Assessment
Consider detectability if applicable

(used in some tools)
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 17
Content
CONSIDERATIONS

Risk Assessment: Risk Analysis
Often data driven
Keep in mind:
Statistical approach may or may not be used
Maintain a robust data set!

Start with the more extensive data set and reduce it
Trend and use statistics (e.g. extrapolation)
Comparing between different sets requires compatible
data
Initiate Quality
Risk Assessment
Risk Communication
Data must be accessible
Risk Analysis
Risk Evaluation
Data must be reliable
Risk Identification
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 18
Content

Risk Assessment: Risk Evaluation
What is the risk?
Compare the identified and analysed risk
against given risk criteria
Consider the strength of evidence
for all three of the fundamental questions
> What might go wrong?
Initiate Quality
> What is the likelihood (probability) it will go wrong?
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
> What are the consequences (severity)?
Risk Assessment
July 2006, slide 19
Content
CONSIDERATIONS

Risk Assessment: Risk Evaluation
A picture of the life cycle
Probability
x Detectability
occurences
driven by
the
number
of trials
past
today
Degree
prepared
by some members of the ICH Q9 EWG for example only; not an official policy/guidance
of
belief
x Severity
Impact
Can you find it?
Data refers to
Frequency
of
= Risk Priority Number
future time
July 2006, slide 20
Content

Risk Control: Decision-making activity
Is the risk above an acceptable level?
What can be done to reduce or eliminate risks?
What is the appropriate balance
between benefits, risks and resources?
Are new risks introduced as
a result of the identified
risks being controlled?
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 21
Content
CONSIDERATIONS

Risk Control: Residual Risk
The residual risk consists of e.g.
> Hazards that have been assessed and
risks that have been accepted
> Hazards which have been identified but
the risks have not been correctly assessed
> Hazards that have not yet been identified
> Hazards which are not yet linked to the patient risk
Initiate Quality
Is the risk reduced to an acceptable level?
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
> Fulfil all legal and internal obligations

> Consider current scientific knowledge & techniques
Risk Assessment
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 22
Content

Risk Control: Risk Reduction
Mitigation or avoidance of quality risk
Elimination of risks, where appropriate
Focus actions on severity and/or probability
of harm; dont forget detectability
It might be appropriate to revisit the
risk assessment during the life cycle
for new risks or increased significance
of existing risks
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 23
Content

Risk Control: Risk Acceptance
Decision to
> Accept the residual risk
> Passively accept non specified residual risks
May require support by (senior) management

> Applies to both industry and competent authorities
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
Will always be made on a case-by-case basis
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
Risk Evaluation
July 2006, slide 24
Content
CONSIDERATIONS

Discuss the appropriate balance between
benefits, risks, and resources
Focus on the patients interests and
good science/data
Risk acceptance is not
Initiate Quality
Risk Assessment
Risk Identification
Risk Communication
Risk Analysis
Risk Evaluation
> Inappropriately interpreting

data and information
> Hiding risks from management /
competent authorities
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 25
Content
What is an acceptable risk?

Who has to accept risk?
Decision Maker(s)
> Person(s) with the competence and authority
to make appropriate and timely
quality risk management decisions
Stakeholder
> Any individual, group or organization
that can be affected by a risk
> Decision makers might also be stakeholders
> The primary stakeholders are the patient, healthcare professional,
regulatory authority, and industry
(ICH Q9, definition)
> The secondary stakeholders are
patient associations, public opinions, politicians
July 2006, slide 26
Content
EXAMPLE

A Risk
Acceptance process
1/3
Risk reduction step

finished
Finish baseline for
risk acceptance decision
risk identification, risk analysis,
risks evaluation, risks reduction
Stakeholders
involved as appropiate?
No
Yes
No
All identified
risks assessed?
Risk Identification
Risk Analysis
Risk Evaluation
Yes
Initiate Quality
Risk Assessment
Risk Communication
Revisit
risk assessment step
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 27
Content
4. General
Quality
Risk
Management
Process
EXAMPLE
Measures/
actions needed?
Yes
Evaluate measures
on severity, probability, detectability
Check needed resources

e.g. employee, money
A Risk
Acceptance
process
2/3
No
Measures / Actions
appropriate?
Revisit
risk reduction step
No
Yes
Other hazards
caused?
Yes
Initiate Quality
Risk Assessment
Risk Identification
No
Risk Communication
Is a risk
reducible?
Risk Analysis
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 28
Content
EXAMPLE

A Risk Acceptance process 3/3
Is a risk
reducible?
No
Yes
Revisit
risk assessment step
No
Accept the
residual risk?
Yes
Advantage
outweighs risk?
Yes
No
Accept risk
Sign off documentation
Risk not acceptable

Sign off documentation
Initiate Quality
Ready for communication
Risk Assessment
Risk Identification
Risk Communication
Risk Analysis
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 29
Content

Risk Communication
Bi-directional sharing of information
about risk and risk management
between the decision makers and others
Communicate at any stage of the QRM process
Communicate and document
the output/result of the QRM process appropriately
Communication need not be carried out
for each and every individual risk acceptance
According to ICH Q9
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
Use existing channels as specified in

regulations, guidance and SOPs
Initiate Quality
Risk Assessment
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 30
Content
CONSIDERATIONS

Risk Communication
Exchange or sharing of information, as appropriate
Sometimes formal sometimes informal
> Improve ways of thinking and communicating
Increase transparency
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
Risk Evaluation
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 31
Content
CONSIDERATIONS
Quality risk management
Communication
facilitates trust
and understanding
Regulators
operation
Industry
operation
- Reviews
- Inspections
- Submissions
- Manufacturing
July 2006, slide 32
Content

Risk review: Review Events
Review the output / results of the QRM process
Take into account new knowledge and experience
Utilise for planned or unplanned events
Implement a mechanism to review or monitor events
Reconsideration of risk acceptance decisions,
as appropriate
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 33
Content
One method
all inclusive?
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Cartoon: Zurich Insurance Inc.

Risk Evaluation
Review Events
July 2006, slide 34
Content
CONSIDERATIONS
Expectations on methods and tools

Supports science-based decisions
A great variety are listed but other existing or
new ones might also be used
No single tool is appropriate for all cases
Specific risks do not always require the same tool
Using a tool the level of detail of an investigation will
vary according to the risk from case to case
Different companies, consultancies and competent
authorities may promote use of different tools based
on their culture and experiences
July 2006, slide 35
Content
CONSIDERATIONS
Contributing items to manage quality risks

System Risk (facility & people)
> e.g. interfaces, operators risk, environment,
components such as equipment, IT, design elements
System Risk (organisation)

> e.g. Quality systems, controls, measurements,
documentation, regulatory compliance
Process Risk
> e.g. process operations and quality parameters
Product Risk (safety & efficacy)

> e.g. quality attributes:
measured data according to specifications
July 2006, slide 36
Content

Supports a scientific and practical approach to
decision-making
Accomplishing steps of the QRM process
> Provides documented, transparent and
reproducible methods
> Assessing current knowledge
> Assessing probability, severity and
sometimes detectability
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 37
Content

Adapt the tools for use in specific areas
Combined use of tools may provide flexibility
The degree of rigor and formality of QRM
> Should be commensurate with the complexity and /
or criticality of the issue to be addressed and
reflect available knowledge
Informal ways
Initiate Quality
Risk Assessment
> empirical methods and / or

internal procedures
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 38
Content
Annex I: Risk Management Methods and Tools

Provides a general overview of
and references for some of the primary tools
Might be used in QRM by industry and regulators
This is not an exhaustive list
No one tool or set of tools is applicable to every
situation in which a QRM procedure is used
For each of the tools
> Short description & reference
> Strength and weaknesses
> Purely illustrative examples
Initiate Quality
Risk Assessment
Risk Identification
Risk Analysis
Risk Communication
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 39
Content
CONSIDERATIONS
Overview: Some tools and their key words

Failure Mode Effects Analysis (FMEA)
> Break down large complex processes into manageable steps
Failure Mode, Effects and Criticality Analysis (FMECA)

> FMEA & links severity, probability & detectability to criticality
Fault Tree Analysis (FTA)

> Tree of failure modes combinations with logical operators
Hazard Analysis and Critical Control Points (HACCP)

> Systematic, proactive, and preventive method on criticality
Hazard Operability Analysis (HAZOP)

> Brainstorming technique
Preliminary Hazard Analysis (PHA)

> Possibilities that the risk event happens
Risk Analysis
Risk Evaluation
Risk Communication
> Compare and prioritize risks with factors for each risk
Risk Identification
Risk ranking and filtering
Initiate Quality
Risk Assessment
unacceptable
Risk Control
Risk Reduction
Risk Acceptance

Risk Review
Review Events
July 2006, slide 40
Content

Supporting statistical tools
> Acceptance Control Charts (see ISO 7966)
> Control Charts (for example)
Control Charts with Arithmetic Average and
Warning Limits (see ISO 7873)

Cumulative Sum Charts; CuSum (see ISO 7871)
Shewhart Control Charts (see ISO 8258)
Weighted Moving Average
> Design of Experiments (DOE)

Pareto Charts
> Process Capability Analysis
Initiate Quality
Risk Assessment
Risk Identification
> Histograms
Risk Analysis
Risk Communication
> Use others that you are familiar with.

unacceptable
Risk Control
Risk Reduction
Risk Acceptance

ICH Q9
Risk Evaluation
Risk Review
Review Events
July 2006, slide 41
Content
CONSIDERATIONS
Q9 does not provide

drivers licences
July 2006, slide 42
Content
6. Integration into
Industry and Regulatory Operations
Foundation for science-based decisions
Does not obviate industrys obligation
to comply with regulatory requirements
May affect the extent and level
of direct regulatory oversight
Degree of rigor and formality commensurate with
the complexity and/or criticality of the issue
Implement QRM principles when updating
existing guidelines
ICH Q9
July 2006, slide 43
Content

This Annex is intended to identify potential uses of quality
risk management principles and tools by
industry and regulators.
However, the selection of particular risk management tools
is completely dependent upon specific facts and
circumstances.
These examples are provided for illustrative purposes and
only suggest potential uses of quality risk management.
This Annex is not intended to create any new expectations
beyond the current regulatory requirements.
ICH Q9 Introduction to Annex II
July 2006, slide 44
Content

Quality risk management as part of
Integrated quality management
> Documentation
> Training and education
> Quality defects
> Auditing / Inspection
Competent
authorities
Industry
> Periodic review

> Change management / change control
> Continual improvement
July 2006, slide 45
Content
Annex II:Potential opportunities

for conducting quality risk management
Quality risk management as part of
Regulatory operations
> Inspection and assessment activities
Competent
authorities
Industry operations
>
>
>
>
>
>
Development
Facilities, equipment and utilities
Materials management
Production
Laboratory control and stability testing
Packaging and labelling
Industry
Competent
authorities
July 2006, slide 46
Content
IS
ANALYS
T`?
HA
Preliminary Hazard Analysis
PHA
FTA
Fault Tree Analysis

Failure Mode, Effects & Criticality Analysis
FMECA
Failure Mode Effect Analysis
FMEA
Hazard Operatibility Analysis
HAZOP
Hazard Analysis & Critical Control Points
ICH Q9
Quality Risk
Management
TOOLS
HACCP
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Peter Gough, Stephan Roenninger,

ICH Q9 : Quality Risk Management - an update
Regulatory Affairs Journal, 16, 2005, 91-93
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prepared by some members of the ICH Q9 EWG for example

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anHoffmann-La
official policy/guidance
J.only;
Arce,
Roche
Bill Paulson, ICH Q9 Provides Implementation

Framework for Quality Risk Management
Gold Sheet, 39, May 2005
July 2006, slide 47
Content
Initiate

Risk Assessment
Risk Identification
Risk Analysis
unacceptable
Risk Control
Risk Reduction
Risk Acceptance
Risk Communication
Risk Evaluation
Output / Result of the

Risk Review
Review Events
Use the right risk expression

please!
July 2006, slide 48

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Content

ICH Q9 QUALITY RISK MANAGEMENT

July 2006, slide 1

Purpose of this part

To guide through the content of the ICH Q9 document

July 2006, slide 2

ICH Q9: Quality Risk Management (QRM)

July 2006, slide 3

July 2006, slide 4

July 2006, slide 5

July 2006, slide 6

July 2006, slide 7

3. Principles of Quality Risk Management

The level of effort,

July 2006, slide 8

4. General Quality Risk Management Process

July 2006, slide 9

Risk Management tools

Output / Result of the

July 2006, slide 10

4. General Quality Risk Management Process

July 2006, slide 11

4. General Quality Risk Management Process

July 2006, slide 12

4. General Quality Risk Management Process

Then assemble background information and/ or data

Output / Result of the Quality

Risk Management tools

> Specify a timeline, deliverables and

July 2006, slide 13

When to apply Quality Risk Management?

Are there clear rules

1. What might go wrong?

Can you answer

Risk assessment not required

Initiate Risk assessment

Select a Risk Management tool

(risk identification, analysis & evaluation)

(if appropriate e.g. see ICH Q9 Annex I)

Run risk control

Carry out the

(e.g. Standard Operating Procedures)

(select appropriate measures)

Document the steps

Based on K. Connelly, AstraZeneca, 2005

July 2006, slide 14

4. General Quality Risk Management Process

Output / Result of the Quality

Risk Management tools

Note: People often use terms

July 2006, slide 15

4. General Quality Risk Management Process

> informed opinions

> concerns of stakeholders

Output / Result of the Quality

Risk Management tools

July 2006, slide 16

4. General Quality Risk Management Process

Consider detectability if applicable

Output / Result of the Quality

Risk Management tools

July 2006, slide 17

4. General Quality Risk Management Process