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Training Program on
Quality Risk Management
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Quality Risk Management
Introduction : Risk Management
“Quality risk Management is a systematic approach for the assessment,
control, communication and review of risks to the quality of the drug
substance across the product life cycle.”
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Quality Risk Management
Risk Management: Regulatory Prospective
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.2 Initiating QRM Process
Quality risk management should include systematic
process designed to coordinate, facilitate and
improve science based decision making with respect
to risk.
Quality risk management include systematic process
designed to coordinate, facilitate and improve
science based decision making with respect to risk.
(Section 6.5.1)
SOP# CDPL/SOP/QA/032/06
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Quality Risk Management
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.3 : Risk Assessment
Risk Assessment consists
of following steps:
1.
Risk identification
2.
Risk Analysis
3.
Risk Evaluation
Risk Assessment consists
of following steps:
1.
Risk identification
2.
Risk Analysis
3.
Risk Evaluation
(Section 6.6.4)
SOP# CDPL/SOP/QA/032/06
Risk Management: Regulatory Prospective
5
Quality Risk Management
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.4 Risk Control
Risk control includes decision making to reduce
and/or accept risks :
The purpose of risk control is to reduce the risk to an
acceptance level.
Risk control (Risk reduction & Risk acceptance): Risk
control includes decision making to reduce and/or
accept risks :
(Section 6.7)
SOP# CDPL/SOP/QA/032/06
Risk Management: Regulatory Prospective
6
Quality Risk Management
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.4 Risk Control
Risk control might focus on following question:
Is Risk above acceptable level?
What can be done to reduce or eliminate risks?
What is appropriate balance among benefits, risks
and resources?
Are new risk introduced as a results of the
identified risk being controlled ?
Risk control might focus on following question:
Is Risk above acceptable level?
What can be done to reduce or eliminate risks?
What is appropriate balance among benefits, risks
and resources?
Are new risk introduced as a results of the
identified risk being controlled ?(Section 6.7.1)
SOP# CDPL/SOP/QA/032/06
Risk Management: Regulatory Prospective
7
Quality Risk Management
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.4 Risk Control
Risk reduction:
Focuses on processes for mitigation
or avoidance of quality risk when it exceeds a
specified acceptable level. Risk reduction might
include actions taken to mitigate the severity and
probability of harm. Processes that improve the
detectability of hazards and quality risk.
Risk reduction: Focuses on processes for mitigation
or avoidance of quality risk when it exceeds a
specified acceptable level. Risk reduction might
include actions taken to mitigate the severity and
probability of harm. Processes that improve the
detectability of hazards and quality risk.
(Section 6.7.2)
SOP# CDPL/SOP/QA/032/06
Risk Management: Regulatory Prospective
8
Quality Risk Management
ICH Q9
A
t Coral Drugs Pvt Ltd
Section 4.4 Risk Control
Risk acceptance:
is a decision to accept risk. Risk
acceptance can be a formal decision to accept the
residual risk.
Risk acceptance: It is formal decision to accept the
residual risk.
(Section 6.7.3)
SOP# CDPL/SOP/QA/032/06
Risk Management: Regulatory Prospective
9
Quality Risk Management
ICH Q9
t Coral Drugs Pvt Ltd
Section 4.5 Risk Communication
Risk Communication:
is the sharing of information
about risk and risk management between the
decision makers and others.
Risk Management: Regulatory Prospective
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Quality Risk Management
Risk Management: Regulatory Prospective
ICH Q9
t Coral Drugs Pvt Ltd
Section 4.6 Risk Review
Risk management should be an ongoing part of the
Quality management process. A mechanism to review
or monitor events should be implemented.
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Quality Risk Management
Risk Management: Regulatory Prospective
ICH Q9
t Coral Drugs Pvt Ltd
Section 5 Risk Management Methodology
Traditionally, risks to quality have been assessed and
managed in variety of informal ways (empirical and/
or internal procedures). Additionally, the
pharmaceutical and regulators can assess and manage
risk using recognized risk management tools and / or
internal procedures.
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Quality Risk Management
Risk Management: Regulatory Prospective
ICH Q9
t Coral Drugs Pvt Ltd
Section 5 Risk Management Methodology
Non
-exhaustive list of some tools:
•
Basic risk management facilitation methods
(flowcharts, check sheet etc.)
•
Failure Mode Effects Analysis (FMEA)
•
Failure Mode, Effects and Criticality Analysis
(FMECA)
•
Fault Tree Analysis (FTA)
-exhaustive list of tools:
Basic risk management facilitation methods
(flowcharts, check sheet etc.)
Failure Mode Effects Analysis (FMEA)
Failure Mode, Effects and Criticality Analysis
(FMECA)
Fault Tree Analysis (FTA)
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Quality Risk Management
Risk Management: Regulatory Prospective
ICH Q9
t Coral Drugs Pvt Ltd
Section 5 Risk Management Methodology
Non
-exhaustive list of some tools:
•
Hazard Analysis and Critical Control Points
(HACCP)
•
Hazard Operability Analysis (HAZOP)
•
Preliminary Hazard Analysis (PHA)
•
Risk ranking and filtering
•
Supporting Statistical tools
-exhaustive list of tools:
Hazard Operability Analysis (HAZOP)
Preliminary Hazard Analysis (PHA)
Risk ranking and filtering
Supporting Statistical tools
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Quality Risk Management
• "Quality Risk Management is a systematic process for the assessment,
control, communication and review of risks to the quality of the medicinal
product across the product lifecycle." (ICH Q9)
What is Quality Risk Management
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Quality Risk Management
Typical QRM Process
Risk Review
R
i
s k
C
o
m
m
un
i
c
a
ti
on
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
Quality Risk Management Process
R
i
sk
M
a
n
a
g
e
m
e
nt
t
oo
l
s
• What might go
wrong or has
gone wrong?
• What is
likelihood or
probability?
• What are the
consequences
(severity)?
• What is the level
of risk? Any
mitigating
factors?
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Quality Risk Management
• "A systematic process of organizing information to support a risk decision to be made within a risk
management process. It consists of the identification of hazards and the analysis and evaluation of risks
associated with exposure to those hazards." (ICH Q9)
Risk Assessment
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Quality Risk Management
Risk identification
Use of information to identify hazards or potential risks
Historical data, theoretical analysis, informed opinions
Risk analysis
Estimation of risk associated with identified hazards
Qualitative or quantitative
Links probability and severity
In some tools, includes detectability
Risk assessment terms
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Quality Risk Management
• A simple qualitative tool:
Risk analysis - probability
P – Probability of Occurrence
Likely to occurHigh
May occurMedium
Unlikely to occurLow
Very unlikely to occurRemote
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Quality Risk Management
• A simple qualitative tool:
Risk analysis - severity
S – severity level if event occurs
Serious GMP non-compliance
Patient injury possible
Critical
Significant GMP non-compliance
Impact on patient possible
Moderate
Minor GMP non-compliance
No patient impact
Minor
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Quality Risk Management
• A simple qualitative tool:
Risk analysis – detectability
D – Modify evaluated risk according to existing
detection controls:
the control is likely to detect the
negative event or its effects
High
the control may detect the
negative event or its effects
Medium
the control is not likely to detect
the negative event or its effects
Low
no detection control in place
Zero
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Quality Risk Management
Risk assessment terms
• Risk evaluation
-Compares identified and analysed risk against criteria
-Considers probability, severity and detectability
-Output can be qualitative (high, medium or low)
-Output can be quantitative using RPN no. (Risk Priority Number) (probability x severity x detectability)
-Quantitative provides a relative ranking – prioritises risk
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Quality Risk Management
• A simple risk table with risk acceptability criteria:
Risk evaluation
Risk = P x S
CriticalModerateMinor
Severity
Probability
Intolerable riskIntolerable riskUnacceptable
risk
High
Intolerable riskUnacceptable riskAcceptable risk
Medium
Unacceptable
risk
Acceptable riskAcceptable risk
Low
Acceptable riskAcceptable riskAcceptable riskRemote
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Quality Risk Management
Risk definitions:
Intolerable – work to eliminate the negative event or
introduce detection controls is required as a priority
Unacceptable – work to reduce the risk or control the
risk to an acceptable level is required
Acceptable – the risk is acceptable and no risk
reduction or detection controls are required
Risk evaluation
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Quality Risk Management
Risk Control Terms
Risk reduction
Actions taken to lessen the probability of occurrence of harm and the severity
of that harm
Typically CAPA and change control
Risk acceptance
The decision to accept risk
If risk reduction action taken, follows re-analysis and evaluation
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Quality Risk Management
Risk Review
"Review or monitoring of output/results of the risk management process considering (if
appropriate) new knowledge and experience about the risk." (ICH Q9)
Ensures nothing has changed to affect the QRM assumptions, output and
conclusions
Consider during product review
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Quality Risk Management
• Basic risk management facilitation methods (flowcharts, check sheets etc.);
• Failure Mode Effects Analysis (FMEA);
• Failure Mode, Effects and Criticality Analysis (FMECA);
• Fault Tree Analysis (FTA);
• Hazard Analysis and Critical Control Points (HACCP);
• Hazard Operability Analysis (HAZOP);
• Preliminary Hazard Analysis (PHA);
• Risk ranking and filtering;
• Supporting statistical tools.
QRM tools – some of them!
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Quality Risk Management
Example :- FMEA Tree - Onion
A layered approach is highly recommended as FMEA can get complex.
FMEA are like ONIONS/LAYERS. Each layer is more detailed
Each layer is closer to the root cause
But ... do too many, and you will cry.
Full FMEA is not simple or quick, ther efore where you can, use a more qualitative
approach
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Quality Risk Management
Example :- FMEA Form
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Quality Risk Management
Example :- Fish Bone / Ishikawa Diagram
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Quality Risk Management
Potential Application
• Quality Management (e.g. self-inspection, training, complaints, deviations, change
control)
• Development (ICH Q8)
• Facilities, Equipment and Utilities (e.g. design, qualification, hygiene, calibration,
computers)
• Materials Management (e.g. supplier assessment, storage)
• Production (e.g. validation, in-process sampling and testing)
• Laboratory Control and Stability Studies (e.g. OOS, retest periods, validation)
• Packaging and Labeling (e.g. package design, label control)
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Quality Risk Management