This document provides an overview of Quality Risk Management (QRM) in the pharmaceutical industry. It discusses the key principles and general process of QRM, including risk assessment, control, communication and review. The three main steps in the QRM process are risk identification, analysis and evaluation to assess risks, followed by risk control measures to reduce, accept or mitigate risks, and risk review to monitor risks over time. QRM aims to systematically minimize risks to product quality throughout a drug's lifecycle.

1. QRM in drug analysis
Pharmaceutical Analysis
Assignment
Post Basic pharmacy
GROUP 3

2. 0utline
Introduction to QRM
Principles of QRM
General QRM Process
Risk Management Methodology
Potential Applications of QRM
Integration of QRM in to industries & regulatory operation
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3. Introduction
• QRM is the overall & continuing process of minimizing risks to
product quality throughout its life-cycle
• to optimize its benefit/risk balance
• It is a systematic process for the assessment, control, communication
& review of risks
• It can be applied both proactively & retrospectively
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4. A Vision of the future becomes fact
Old Approach New Approach Remarks
Broad Concept
Quality decisions divorced
from science and risk
evaluation.
Adherence to filing
commitments.
Quality decisions and filing
committments based on
Process Understanding
and Risk Management.
Quality by Design.
Design Space concept
introduced to integrate
process knowledge with
regulatory evaluation.
Quality
Post-factum sampling and
quality testing.
Process Validation.
Management of variability
Process control focused on
critical attributes.
Continuous Quality
Verification.
Quality by design definition
applied. Measure critical
process parameters to control
output product quality.
Systems
Systems designed to inhibit
changes & minimize business
risks. Discourages
improvement & innovation.
Changes managed within
company's quality system.
Real time batch release
feasible.
Regulators and industry place
higher reliance / trust /
understanding on systems.
Multidisciplinary evaluation
and decision making.
Regulatory
Compliance focus.
Changes require prior
approval.
Regulatory scrutiny adjusted
to level of Process
Understanding. Continuous
improvement allowed
within Design Space.
Requires mechanisms to
communicate Process
Understanding data
("inspectable rather than
reviewable") .

5. “risk-based”
concepts and
principles
The new paradigm(ICH)

6. Principles of QRM
 Two primary principles of QRM are:
1) The evaluation of the risk to quality should be based on scientific
knowledge & ultimately link to the protection of the patient
2) The level of effort , formality & documentation of the QRM process
should be commensurate with the level of risk
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7. QRM principles…
Not all risks can be eliminated- thus we must manage and mitigate
those risks that do exist
Not all risks are readily apparent- a hidden risk can often pose a
greater threat to our business than those we know and can manage
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8. QRM process
 Has three steps:
oRisk assessment (ID, analysis, evaluation)
oRisk control (reduction, acceptance)
oRisk review
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9. QRM process…
(ICH Q9)
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10. Definitions
Quality
Risk
Degree to which a set
of inherent properties
of a product, system or process
fulfills requirements
combination of the
probability of occurrence of harm and
the severity of that harm
Systematic process for the assessment,
control, communication and review
of risks to the quality of the
drug (medicinal) product
across the product lifecycle
Management
QRM
ICH Q9

11. Uncertainty and Quality Risk Management
Hazard
may
cause harm
Hazard
may not
cause harm
uncertainty
Hazard
is less likely to
cause harm
Manage risks
in relation to
probability &
severity
Lack of, or inadequate knowledge

12. Risk Management as a discipline
Provides multiple benefits
• Understand and influence the factors (hazards)
which impact regulators and industry business
• Create awareness and a culture
• Supports an effective pro-active behaviour
• Open factual dialogue
• Make decisions traceable and consistent
• Provide assurance
• Risks are adequately managed
• Compliance to external and internal requirements
• Recognise risks at a desired level
• Zero risk not possible

13. QRM process…
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 or data on the potential hazard, harm or
human health impact relevant to the risk
• Identify a leader and necessary resources
• Specify a timeline, deliverables and appropriate level of decision making for the
QRM process
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14. Should risks
be assessed?
Are there clear rules
for decision making?
e.g. regulations
Yes
“no RM“
Risk assessment not required
(No flexibility)
Follow procedures
(e.g. Standard Operating Procedures)
Document results,
decisions and actions
QRM process...
When to apply Quality Risk Management?
Based on K. Connelly, AstraZeneca, 2005
1. What might go wrong?
2. What is the likelihood (probability)
it will go wrong?
3. What are the consequences (severity)?
No or
justification needed
Can you answer
the risk assessment
questions?
Yes
“informal RM“
Initiate Risk assessment
(risk identification, analysis & evaluation)
Run risk control
(select appropriate measures)
Agree on a team
(small project)
Select a Risk Management tool
(if appropriate e.g. see ICH Q9 Annex I)
No
“formal RM“
Carry out the
quality risk management process
Document the steps

15. QRM Process…
Risk assessment
• involves ID, analyzing & evaluating potential
failures in the process, facility, system or product.
 3 fundamental questions
• Risk Identification
What might go wrong?
• Risk Analysis
What is the likelihood (probability) it will go wrong?
• Risk Evaluation
What are the consequences (severity)?
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16. QRM process…
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
• concerns of stakeholders
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17. QRM Process....
“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
• Consider detectability if applicable (used in some
tools)
Risk Assessment: Risk Analysis
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18. QRM Process....
Risk analysis- probability -as simple
qualitative tool
P- Probability of
occurrence
• High
• Medium
• Low
• Remote
Interpretation
• Likely to occur
• May occur
• Unlikely to occur
• Very unlikely to occur
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19. QRM process…
Risk Analysis- Detectability
High- The control is likely to detect the negative event or its
effect
Medium- The control may detect the negative event or its
effects
Low- the control is not likely to detect the negative event or its
effects
Zero- no detection control in place
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20. QRM Process...
“What is the risk?”
• Compare the identified & analyzed risk against a given risk
criteria
• Consider the strength of evidence for all three of the
fundamental questions
• What might go wrong?(detectability)
• What is the likelihood (probability) it will go wrong?
• What are the consequences (severity)?
• RPN=probability x severity x detectability
Risk Assessment: Risk Evaluation
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21. Output/result of Risk Assessment
 Output can be qualitative (high, medium, low),
 Output can be quantitative (probability x severity x detectability),
 Quantitative provides a relative ranking- prioritizes risk(RPN)
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22. Simple risk table with risk acceptability criteria
Risk= P X S
PROBABILITY
SEVERITY
Minor Moderate Critical
High Unacceptable risk Intolerable risk Intolerable risk
Medium Acceptable risk Unacceptable risk Intolerable risk
Low Acceptable risk Acceptable risk Unacceptable risk
Remote Acceptable risk Acceptable risk Acceptable risk
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23. Quality risk assessment – using FMEA
Example: to identify critical manufacturing steps that will require
validation:
Acceptance criteria: RPN for A= 1X2X2= 4 for B =3x3x3=27>>
validation is critical (JUST AN EXAMPLE!)
Step A 1X2X2=4
Assessment
Category
1 2 3
Probability
of
occurrence
Low Medium High
Severity (S) Minor Moderate Critical
Detectability High Medium Low
Step B 3X3X3=27
1 2 3
Low Medium High
Minor Moderate Critical
High Medium Low
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24. QRM Process...
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 b/n benefits, risks &
resources?
 Are new risks introduced as a result of the identified
risks being controlled?
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25. QRM Process...
Risk Control: Risk Reduction
 Mitigation or avoidance of quality risk
 Focus actions on severity, probability of harm &
detectability
 It might be appropriate to revisit the risk asst during the
life cycle for new risks or increased significance of
existing risks
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26. QRM Process...
Risk Control: Risk Acceptance
 Decision to
>Accept the residual risk
• Discuss the appropriate balance b/n benefits, risks &
resources
• Focus on the patients’ interests & good science/data
• May require support by (senior) management
• Risk acceptance is not
• Inappropriately interpreting data & information
• Hiding risks from management / competent authorities
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27. QRM Process...
Risk Control: Risk Acceptance
Who has to accept risk?
• Decision Maker(s)
• Person(s) with the competence and authority to make
appropriate and timely QRM decisions
• Stakeholder
• Any individual, group or organization that can be affected
by a risk
• Decision makers might also be stakeholders
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28. QRM Process...
Risk Communication
• Bi-directional sharing of information about risk & risk
management between the decision makers & others
• Communicate at any stage of the QRM process
• Communicate & document the output/result of the QRM
process appropriately
• Improve ways of thinking and communicating
• Increase transparency
• facilitates trust & understanding
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29. QRM Process...
Risk review: Review Events
• Review the output / results of the QRM process
• Take into account new knowledge and experience
• Implement a mechanism to review or monitor events
• Reconsideration of risk acceptance decisions, as
appropriate
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30. Risk Management Methodology
• Supports a scientific & practical approach to decision-making
• Accomplishing steps of the QRM process
• Provides documented, transparent & reproducible methods
• Assessing current knowledge
• Assessing probability, severity & sometimes detectability
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31. Overview: Some tools and their key
words
• Basic RMFM (flowcharts, check sheets, process mapping,
cause & effect diagrams or Ishikawa diagram or fish bone
diagram).
• 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 ranking and filtering
• Compare and prioritize risks with factors for each risk
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32. Potential Applications for QRM
• Documentation
• Training and education
• Quality defects
• Auditing / Inspection
• Periodic review
• Change management / change control
• Continual improvement
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33. Potential applications …
Documentation:
 To develop the content for SOPs, guidelines, etc
Training and Education
 To identify training, experience, qualification, and physical
abilities that allow personnel to perform an operation reliably
without any adverse impact on the quality of the product
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34. Potential applications…
Quality Defects
 To provide the basis for identifying, evaluating, and
communicating the potential quality impact of;
a suspected quality defect, complaint, trend, deviation, investigation,
OOS result etc,
 To facilitate risk communications & determine appropriate
action;
 to address significant product defects, in conjunction with regulatory
authorities (e.g., recall).
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35. Potential applications …
Auditing/inspection
 To define the frequency and scope of audits, both internal and
external taking into account factors such as :
oExisting legal requirements
oOverall compliance status and history of company or facility
oComplexity of the site
oComplexity of manufacturing process
oResults of previous audits/ inspections
oMajor changes of buildings, equipment, processes, key
personnel
oNumber and significance of quality defects
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36. Potential applications …
Periodic review
 To select, evaluate, and interpret trend results of data within the
product quality review
management/change control
 To evaluate the impact on product quality of changes to the
facility, equipment, material, manufacturing process, or
technology transfers.
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37. Potential applications …
Hygiene aspects in facilities
 To protect the products from environmental hazards, including
chemical, microbiological and physical hazards (eg determining
appropriate clothing and gowning, hygiene concerns
Qualification of facility/equipment/utilities
 To determine the scope and extent of qualification of facilities,
buildings, and production equipment and/or laboratory
instruments (including proper calibration methods)
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38. Integration of QRM into industry & Regulatory Operations
Example for industry operations and activities
Development
Facility, equipment, and utilities
Materials management
Production
Laboratory control and stability testing
Packaging and labeling
Example s for regulatory operation
Inspection and assessment activities
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39. Group Members Name
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40. Thankyou!!