In the complex life of Pharmaceutical industries, compliance could get easier if we understand and apply an "Easy" method for a Quality Risk Management! I have practiced many tools, and came up with my selected easy to implement one, IMHO! feedback?: mhalawani@hotmail.com

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My perspective to
Risk Management

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Example: FDA’s Inspection Risk-
based Approach
• Sept. ’04 - Risk-
based Method for
Prioritizing CGMP
Inspections
• FDA convened a
panel of experts
• Brainstorming
sessions identified
70 potential risk
factors!

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•SCOPE:
•New Project
•Processes
•Systems and Utilities
•Equipment

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Scheme
Team
approach
Risk Review
RiskCommunication
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
RiskManagementtools
ICH Q9

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Risk Team:
Chaired by the technical sector director, all
technical department managers and who could
attend and be responsible to review, analyze,
and approve CAPA
Risk Owner:
Represented by the process owner who is
responsible for initiating, reporting risk,
conducting its activity and implementation of
CAPA

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Tools for Risk
Management
IDENTIFY:
• Cause-&-Effect
Analysis (Fish bone)
2. Process Mapping /
Flowcharts
ASSESS
1. Brainstorming
2. 5 WHYS?
EVALUATE/MITIGATE
1. FMEA (+RPN)
Other tools:
• QFD
• FTA
• FMECA
• HACCP
• Decision Trees
• Etc.

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Process Flow
S t a r t / E n d P r o c e s s
P r o c e s s S u b r o u t i n e s
D e c i s i o n P o i n t
P r o c e s s A l t e r n a t e P r o c e s s
M a n u a l O p e r a t i o n
P r o c e s s
D e l a y
D e c i s i o n
P o i n t
O f f - p a g e P r o c e s s
S t a r t / E n d P r o c e s s
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Example: Cause-and-Effect
Diagram for the elements of
process validation
Vessel #1
M
A
CHINER
Y
ENVIRO
N
M
ENT
M
EA
SUREM
ENT
M
E
TH
O
D
O
LO
G
Y
M
A
TE
R
IA
LS
M
A
N
P
O
W
E
R
Approved APIs
Approved Excipients
Approved PKG & LBL
QC
Pharm Eningeering
Operations
M
fg.
P
kg.
Validation Policies
Validation SOPs
Validation Approach
M
atrix
3
Batches
Manufacturing
Packaging
Filling
Labeling
M
inor
M
ajor
M
B
R
PRO
T
Surfaces
Air
Controlled Access
G
ow
ning
PPE
VM
P
In Process
Volum
e
Spec.
Density
Release
Stability
A
nalytical
M
icro
A
nalytical
M
icro
H
um
idity
Tem
p.
Changes/
H
r.
Water
P
urified
W
FI
Vessel #2

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Example: Brainstorming how do we clean
equipment & facilities?
Automated
System
(Not in-place)
SIP System
Manually
CIP System
Combination
of methods
How do we
clean it?
No product
residue
No detergent
residue
No micro-
organisms
No dye or
flavor
residues
What are the criteria
for clean?
RISK:
CLEANING
VALIDATION
Equipment
Facilities
Handtools
IMTE
What needs to
be cleaned?
Supppliers
QA
QC Labs
Operations
Who is involved?
(Functionally)

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5WHYS?????

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Imagine!
Risk Management
Quality Risk Management
Quality Systems
Harm
Severity
Stakeholder
Product Life Cycle
GMP Compliance

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Principles of Quality Risk
Management
Two primary principles:
The evaluation of
the risk to quality
should be based on scientific
knowledge (without
preaching the
guidelines!!!)
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

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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
When to apply Quality Risk
Management?
CONSIDERATIONS
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

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The Process Flow
A Risk
Acceptance
process
1/3
Risk Review
RiskCommunication
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
RiskManagementtools
EXAMPLE
Finish baseline for
risk acceptance decision
risk identification, risk analysis,
risks evaluation, risks reduction
Risk reduction step
finished
Yes
Stakeholders
involved as appropiate?
Revisit
risk assessment step
All identified
risks assessed?
No
Yes
No

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Risk Review
RiskCommunication
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
RiskManagementtools
EXAMPLE
Evaluate measures
on severity, probability, detectability
Check needed resources
e.g. employee, money
Measures / Actions
appropriate?
No
Yes
Revisit
risk reduction step
Other hazards
caused?
Yes
Is a risk
reducible?
No
Measures/
actions needed?
Yes
No

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Risk Review
RiskCommunication
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
RiskManagementtools
EXAMPLE
Accept the
residual risk?
Ready for communication
Accept risk
Sign off documentation
Is a risk
reducible?
Yes
Advantage
outweighs risk?
Yes No
Yes
No
Risk not acceptable
Sign off documentation
Revisit
risk assessment step
No

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Quality risk management
Industry
operation
- Submissions
- Manufacturing
Regulators
operation
- Reviews
- Inspections
Communication
facilitates trust
and understanding
CONSIDERATIONS

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QUALITY SYSTEM
ICH Q9
Quality Risk
Management
PRINCIPLES PATIENT PROTECTION
EFFORT
PROCESS
ASSESSMENT
CONTROL
COMMUNICATION
IDENTIFICATION
ANALYSIS
EVALUATION
REDUCTION
ACCEPTANCE
REVIEW EVENTS
ACCEPT (RESIDUAL RISK)
INTERD
ISCIPLINAR
Y
TEAM
S
W
HAT`?
PROBABILITYSEVERITY
CRITERIA
Failure Mode, Effects & Criticality Analysis
TOOLS
INFORMAL
HACCP
HAZOP
FMEA
FMECA
FTA
PHA
Hazard Analysis & Critical Control Points
Preliminary Hazard Analysis
Fault Tree Analysis
Failure Mode Effect Analysis
Hazard Operatibility Analysis
QUALITY Mgt.
INDUSTRY
REGULATORY
DOCUMENTATION
TRAINING
AUDITING
CHANGE CONTROL
MATERIALS
PRODUCTIONQ
U
INSPECTION
ASSESSMENT
APPLICATION
RISK
PROBABILITY OF HARM
SEVERITY
CAUSE OF DAMAGE
CAUSE OF HARM
HAZARD
Peter Gough, Stephan Roenninger,
ICH Q9 : Quality Risk Management - an update
Regulatory Affairs Journal, 16, 2005, 91-93
Bill Paulson, ICH Q9 Provides Implementation
Framework for Quality Risk Management
Gold Sheet, 39, May 2005
© J. Arce, F. Hoffmann-La Roche

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RPN
Risk Assessment: Risk Evaluation
A picture of the life cycle
Probability Detectability Severity
past today future
Datarefersto
time
Impact
Canyoufindit?
= Risk Priority Number
x x
• Frequency
of
“occurences”
driven by
the number
of trials
• Degree
of belief
CONSIDERATIONS

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Assign Levels of Probability of Hazard Occurrence
Probabilit
y
This means the Hazard
)3(
Is very likely to occur , more than one time
/ year
)2(
Will Probably occur, one time/ year
)1( Accidental event ,exceptional occurrence
May occur some time , Infrequently, one
time /more than one year

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Assign Hazards Severity Levels
Severity This means the hazard
)3( Possible impact on the manufactured product
and with possible hazard for the patient (end
user)
)2( Possible impact on the manufactured product
but without risk for the patient (end user)
)1( Addressed by applicable GMP, OR without
possible impact on the manufactured product

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Assign Detection Control
Detection This means the Hazard
)3( Absence of system of detection but
detection is still possible by chance
)2( Presence of a single system of detection
which is not 100% reliable
)1( System of multiple and independent
detection tools or a single system of
detection which is 100% reliable

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3-Numerical risk evaluation (RPN value(:
Multiplication product of severity,
frequency and delectability for example:

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•Risk degree assessment and the
equivalent action taken as follows:
RPN
value
Risk
factor
Action taken
1-6 Minor
Accepted
8-12 Major
To be registered in risk register and
closed through 40 working days
unless any other justification
18-27 Critical
To be registered in risk register and
closed through 30 working days
unless any other justification

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EXAMPLE

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