ICH Q9 QUALITY RISK MANAGEMENT(QRM)

ICH Q9 QUALITY RISK MANAGEMENT(QRM) SAIM IKHLAQUE SOLEJA �MPhil Student 2021�Hamdard University

1. ICH Q9
QUALITY RISK
MANAGEMENT
(QRM)
By SAIM IKHLAQUE SOLEJA
MPhil Student
Hamdard University

2. SAIM IKHLAQUE
SOLEJA
MPhil Student 2021
Hamdard University
Email: [email protected]

3. Table ofcontents
1. Introduction
2. Scope
3. Principles of Quality Risk Management
4. General Quality Risk Management Process
5. Risk Management Methodology
6. Integration of QRM process into Industry and Regulatory operations
7. Definitions
8. References
Annex I: Risk Management Methods and Tools
Annex II: Potential Applications for QRM

4. 1.Introduction
WHAT IS RISK?
Effect of uncertainty on objective (Risk
Management guidelines ISO 31000:2018)
The combination of occurrence of harm and the
severity of that harm (ICH Q9 guidelines)
Business wise: it is the probability for loss to the
focal organization.
Regulatory wise: it is the probability for health
damage

5. Harm: Damage to health, including the damage that can
occurfrom loss of product quality or availability.
Hazard: The potential source of harm (ISO/IEC Guide 51).
Severity: A measure of the possible consequences of a
hazard.
Detectability: The ability to discover or determinethe
existence, presence, or fact of a hazard.

6. risk analysis: The estimation of the risk associated with the identified
hazards.
risk assessment: 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
evaluation of risk associated with exposure to those hazards.
risk control: The sharing of information about risk and risk management between
the decisionmaker and other stakeholders.
risk evaluation: The comparison of the estimated risk to given risk criteria using a
quantitative or qualitative scale to determine the significance of the risk.
risk identification: The systematic use of information to identify potential sources
of harm (hazards)

7. Occurrence: Probability of negative events within a fixed time frame.
quality risk management: A systematic process for the assessment, control
communication, and review of risks to the quality of the pharmaceutical
product across the product life-cycle.

8. ❖risk priority number (RPN): A numeric assessment of risk assigned to a
process, or steps in a process, as part of failure mode effects analysis
(FMEA). Each failure mode gets a numeric score that quantifies likelihood
of occurrence, likelihood of detection and severity of impact. The product
of these three scores is the RPN for that failure mode.
❖RPN = severity rating ×occurrence rating ×detection rating.
❖risk review: Review or monitoring of output or results of the risk
management process considering (if appropriate) new knowledge and
experience about the risk.

9. UNPLANNED RISK
ASSESSMENT: An assessment
that is conducted to assess the
impact of a situation that has
already occurred,
PLANNED RISK ASSESSMENT: An
assessment that is conducted in
advance of an activity, either
before any work is conducted or
before further work is conducted.
This enables quality to be built into
activities and risk to be reduced,
e.g. impact of a deviation from normal ways of
working.
e.g. design of high containment facilities for
manufacture of cytotoxic products.

10. 2. Scope
This guideline provides principles and
examples of tools for 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 (including the use of raw materials, solvents,
excipients, packaging and labeling materials in drug
(medicinal) products, biological and biotechnological
products).

11. 3. Principle of
QRM
The level of effort, formality and documentation of
the quality risk management process should be
commensurate with the level of risk.
The evaluation of the risk to quality should be
based on scientific knowledge and ultimately link
to the protection of the patient; and
Two primary principles of quality risk management
are:

12. unacceptable
RiskAssessment
RiskIdentification
Risk Analysis
RiskEvaluation
Initiate
Quality Risk ManagementProcess
Risk
Communication
RiskReview
ReviewEvents
RiskControl
RiskReduction
RiskAcceptance
Output / Result of the
Quality Risk ManagementProcess
Risk
Management
tools
4. General Quality Risk
Management Process
Team
approach

13. 1.Responsibilities.
❖Interdisciplinary teams
❖experts from the appropriate areas (e.g., quality unit, business development,
engineering, regulatory affairs, production operations, sales and marketing,
legal, statistics and clinical) in addition to individuals who are kanowledgeable
about the quality risk management process.
❖Decision makers
2.Initiating a Quality Risk Management Process
❖Define the problem and/or risk question, including pertinent assumptions
identifying the potential for risk;
❖Assemble background information and/ or data on the potential hazard, harm
or human health impact relevant to the risk assessment;
❖Identify a leader and necessary resources;
❖Specify a timeline, deliverables and appropriate level of decision making for
the risk management process.

14. 3. Risk Assessment
1.What might go wrong?
2. What is the likelihood (probability) it will go
wrong?
3. What are the consequences (severity)?
a)Risk identification
b)Risk analysis
c)Risk evaluation

15. •Risk control might focus on the following questions:
•Is the risk above an acceptable level?
•What can be done to reduce or eliminate risks?
•What is the appropriate balance among benefits, risks and resources?
•Are new risks introduced as a result of the identified risks being controlled?
•Risk reduction
•Risk acceptance
4. Risk Control
5.Risk Communication
6.Risk Review

16. 5. Risk Management
Methodology

17. Examples of
common risk
management
tools

18. Risk management toolDescription, attributesPotential applications
Diagram analysis
• Flowcharts
• Check sheets
• Process mapping
• Cause/effect diagrams
Simple techniques that
are commonly used to
gather and organize
data, structure risk
management processes
and facilitate decision
making
Compilation of
observations, trends or
other empirical information
to support a variety of
less complex deviations,
complaints, defaults or
other circumstances

19. Risk management
tool
Description, attributesPotential applications
Risk ranking and
filtering
Method to compare and rank
risks
▪Typically involves evaluation
of multiple diverse quantitative
and qualitative factors for each
risk, and weighting factors and
risk score
▪Compilation of
observations, trends or
other empirical information
to support a variety of less
complex deviations,
complaints, defaults or
other circumstances

20. Risk management
tool
Description, attributesPotential applications
Fault-tree analysis▪Method used to identify all
root causes of an assumed failure
or problem
▪Used to evaluate system or
subsystem failures one at a time,
but can combine multiple causes
of failure by identifying causal
chains
▪Relies heavily on full process
understanding to identify causal
factors
Compilation of
observations, trends or
other empirical information
to support a variety of
less complex deviations,
complaints, defaults or
other circumstances

21. Risk management
tool
Description, attributesPotential applications
Fault-tree analysis▪Method used to identify all
root causes of an assumed failure
or problem
▪Used to evaluate system or
subsystem failures one at a time,
but can combine multiple causes
of failure by identifying causal
chains
▪Relies heavily on full process
understanding to identify causal
factors
▪Investigate product
Complaints
▪Evaluate deviations

22. Risk
management tool
Description, attributesPotential applications
Hazard operability
analysis (HAZOP)
▪Tool assumes that risk events
are caused by deviations from the
design and operating intentions
▪Uses a systematic technique
to help identify potential
deviations from normal use or
design Intentions
▪Access manufacturing
processes, suppliers,
facilities and equipment
▪Commonly used to
evaluate process safety
Hazards

23. Risk management
tool
Description, attributesPotential applications
Hazard analysis and
critical control point
(HACCP)
▪Identify and implement
process controls that
consistently and effectively
prevent hazard conditions from
occurring
▪Bottom-up approach that
considers how to prevent
hazards from occurring and/or
propagating
▪Emphasizes strength of
preventive controls rather than
ability to detect
▪Access manufacturing
processes, suppliers,
facilities and equipment
▪Commonly used to
evaluate process safety
Hazards

24. Risk management
tool
Description, attributesPotential applications
Failure modes effects
analysis (FMEA)
▪Assumes comprehensive
understanding of the process and
that CPPs have been defined
prior to initiating the assessment.
Tool ensures that CPPs will be
met.
▪Assesses potential failure
modes for processes, and the
probable effect on outcomes
and/or product performance
▪Once failure modes are
known, risk reduction actions can
be applied to eliminate, reduce
or control potential failures
▪Evaluate equipment and
facilities; analysea
manufacturing process to
identify high risk steps
and/or critical parameters

25. FISHBONE DIAGRAM
Reference: QUALITY RISK MANAGEMENT to Address Product Impurities By Muhammad Naeem

26. ItemFactor Failure Mode Existing Control
Severity (S)
Probability (P)
Detectability (D)
RPN =
(P x S x D)
Recommended
Action for Risk
Mitigation
Severity (S)
Probability (P)
Detectability (D)
RPN
2
=
(P x S x D)
Human
Operation
Operation does not follow standard
operating procedure (SOP), which
may lead to generation of impurities
Every operator involved in manufacturing
is trained; second person is available to
review critical operation
2124
Hygiene
Personnel involved in production are
unhygienic, which may lead to cross
contamination
All personnel involved in manufacturing
are trained and maintain good hygiene
5115
Gowning
Dirty/used clothing may lead to cross
contamination
As per SOP, operators are given fresh pair
of coveralls at start of shift
5115
Machine
Equipment
qualification
Nonqualified equipment or failure in
qualification status
Equipment is qualified initially and
requalified on defined intervals per the
validation master plan (VMP)
2112
Material
Material of construction is not of
required pharmaceutical grade, which
may lead to cross contamination
Material of construction for all equipment
is of required pharmaceutical grade
5115
Reference: QUALITY RISK MANAGEMENT to Address Product Impurities By Muhammad Naeem

27. “In the fields
ofobservationchance
favors only the
preparedmind”
Louis Pasteur
THANKYOU
If you have any other questions or
need further clarification, simplyemail
meat [email protected]