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A Brief concept to Risk assessment analysis….. (where we stand ?) In context to ICH Q9….
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A Brief concept to Risk assessment analysis…..
(where we stand ?) In context to Q9….
We are living in full of risk…. Risk management not new…
Zero risk does not exist anywhere…
Presented by
Subhakanta Dhal .
Mail [email protected] 1
.
2
Risk of life….
3
Examples of Everyday Risk
POSSIBLE RISK/ EVENT/ SCENARIO
STRATEGIC FINANCIAL
CLINICAL (HEALTHCARE)
OPERATIONAL
Including: Governance, Stakeholder Relationships, Reputation, Environment
Including Capital Management, Budgeting, Revenue and Expenditure, Reporting
Including Human Resources, OH&S, Procurement, Legislative, Asset Management
Changes in services provided Incorrect valuation of capital assets Medication errors Power failure
Loss of customers to private sector companies
Declining market value of assets Terrorist attack/ Bomb threat etc.
Services/ goods not provided within budget
Capital assets not maintained/ deterioration Patient aggression Tender evaluation requirements not defined
Change in public demand for services/ products
Equipment obsolescence Sentinel events Overpayment for goods and services
Change in public demand for services/ products
Customer revenue/ collections targets not met Incorrect diagnosis Failure to comply with procurement legislation/ processes
Loss of customers to other state organisation
Unauthorised and irregular expenditure Infection control procedures not followed Conflicts of interest in tender award process
Political change Wasteful or unproductive expenditure Failure to report incidents Failure/ closure of service provider
Poor market knowledge Changes in funding allocations Patient records not available/incomplete/incorrect
Unethical service provider actions
Change in interest rates Over/ under spending budget allocations Not upto mark of ethical standards Goods/ services not meeting quality requirements
Stakeholders not identified Inaccurate revenue forecasting
Non-delivery of goods and services by supplier
Concept based
• Terminology
• Define- Risk & Type
• ICH and FDA : Expectation
• Identify - what is risk ?
• Measure – how to mitigate risk And how much extend ?
• Improve & Analysis –how to improve ? Specific method ?
• Control – can risk be controlled? If controlled then how ?
• Root cause analysis
• Opportunities & Benefits.
• Potential Applications.
• Future prospective
Case study
• FMEA
Contents
4
ICH Framework (Q8,Q9,Q1O)....
ICH Q8/Q8(R) - Pharmaceutical Development
PAT Guidance
ICH Q9 – Quality Risk Management
ICH Q10 – Pharmaceutical Quality Systems
Product
Design
Process
Design
Scale-up &
Transfer
Commercial
Manufacture
Product Life Cycle
Product
ICH Framework (Q8,Q9,Q1O)....
Product development concept..
In line with Quality Risk Management ?
Risk Review
R i s
k C
o m
m u
n i c
a t i
o n
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 s
k M
a n
a g
e m
e n
t t o o
l s
Product development concept..
Process understanding
Formulation & Process design
Process control Concept
Product release Concept
Review the submission
Regulatory strategy
Manufacturing Concept
Target Product Profile
Drug substance properties; prior knowledge
Proposed formulation and manufacturing process
Determination of
Cause – Effect relationships (Risk Identification with subsequent Risk Analysis)
Risk-based classification (Risk Evaluation)
Parameters to investigate (e.g. by DOE) (Risk Reduction 1. proposal; 2. verified)
FORMULATION
DESIGN SPACE PROCESS
DESIGN SPACE
BY UNIT OPERATION
CONTROL
STRATEGY
Fo
rmu
latio
n u
nd
ers
tan
din
g
Pro
cess u
nd
ers
tan
din
g
Re
-evalu
atio
n a
nd
co
nfirm
atio
n
Re
-evalu
ati
on
an
d c
on
firm
ati
on
Product and process
characteristics on the
final drug product
Review events
Development
De
ve
lop
m.
Op
era
tion
Research
Phase 1
Phase 2
Phase 3
Launch EFPIA PAT TG, 2006
Role of risk Product development concept..
Risk Management approach to focus on critical attributes Q
ua
lity
Att
rib
ute
s
Unit operation
Granulation Drying Blending Tableting Dispensing
Dissolution
Disintegration
Hardness
Assay
Content
Uniformity
Degradation
Stability
Appearance
Identification
Water
Microbiology
Control
Strategy
Formulation
and Process
understanding
Prior
knowledge
Significant
influence
Initial
assessment
First & Second
review cycle
Third
review cycle
EFPIA PAT TG, 2006
11
What Risks Must Be Managed?
Business
Product liability
Regulatory
Risk to safety of
patients, users, handlers
12
Terminology .
Risk: The combination of the probability of occurrence of harm and the severity of that harm .
Risk Acceptance: The decision to accept risk .
Hazard: The potential source of harm.
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 analysis and evaluation of risks associated with exposure to those hazards.
Risk Communication: The sharing of information about risk and risk management between the decision maker and other stakeholders.
Risk Control: Actions implementing risk management decisions .
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) referring to the risk question or problem description
.
13
Terminology
Risk Management: The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating and reviewing risk.
Risk Reduction: Actions taken to lessen the probability of occurrence of harm and the severity of that harm.
Risk Review: Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk.
Severity: A measure of the possible consequences of a hazard.
Stakeholder: Any individual, group or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, healthcare professional, regulatory authority, and industry.
Decision Maker(s):Person(s) with the competence and authority to make appropriate and timely quality risk management decisions.
Detectability:The ability to discover or determine the existence, presence, or fact of a hazard.
Harm: Damage to health, including the damage that can occur from loss of product quality or availability.
ICH Q9 Link back to patient risk
Process
Materials
Design
Manufacturing
Distribution
Patient
Facilities
Opportunities to impact
risk using quality risk
management
ICH and FDA :Expectation
Risk Management across the Product lifecycle for drug (medicinal) products
Research
Preclinical
Phase Clinical
Phases
Launch
Quality ICH Q9
Safety
Efficacy
Manufacturing
& Distribution
GLP
GCP(clinical)
GMP
GDP (Distribution )
End of
life cycle
ICH and FDA :Expectation
ICH and FDA :Expectation
16
FDA Pharmaceutical GMP Initiative
A Challenge to Industry: (FDA announcement 27 Sep. 2004)
At the end of the cGMP Initiative the pharmaceutical community has arrived at a cross-
road; one path goes towards the desired state and the other maintains the current state. The
path towards the desired state is unfamiliar to many while the current state provides the
comfort of predictability. The Agency hopes the pharmaceutical community will choose to
move towards the desired state.
Why was ICH Q9 ( Quality risk management ) needed?
•The evaluation of the risk to quality should be based on scientific knowledge and
ultimately link to the protection of the patient.
•A systematic process for the assessment, control, communication and review of risks to
the quality of the drug product across the product.
•The level of effort, formality and documentation of the quality risk management
process should be commensurate with the level of risk.
•To facilitate moving to the “Desired State”.
•To facilitate communication and transparency.
ICH and FDA :Expectation
17
Regulators evaluate category of risk, based on: • Product, process and facility . • Controls to assess & mitigate risk . • Quality system implementation . Regulators determine ‘risk category’ and modify level of oversight accordingly for: • Post-approval change review . • GMP inspections . Result: • Removal of barriers to continuous improvement . • Efficient use of resources by industry & regulators .
?
The Hurdles Increasing
external
requirements for best practice,
transparency and
compliance • Public / Community
• Governments
• Regulators
• Patients • Investors / Creditors
Growing
complexity and scope of risks
• Globalisation
“Multinational”
• Multi-factor approaches
• Regulatory expectations
• Acceptance of
risk and uncertainty
Increasing
efforts and costs for sustainability
• Documentation
• Projects
• Systems
• Interfaces
ICH and FDA :Expectation…
Initiate
Quality Risk Management Process
Risk Assessment
Risk Control
Risk Review
Risk Identification
Risk Analysis
Risk Evaluation
Risk Reduction
Risk Acceptance
Review Events
Output / Result of the
Quality Risk Management Process
Ris
k C
om
mu
nic
ati
on
Risk
Man
agem
ent T
oo
ls
unacceptable
• Brainstorming • Elementary Cause and Effect
Assignments – Fishbone (Ishikawa)
diagram – Failure mode/effect table • Fault tree analysis
• Process map • Flow charts
• FMEA • FMECA
• Risk ranking
Risk Identification
Risk Analysis
Risk Evaluation
• Process sensors • SOP
• Data flow optimization
Risk Reduction
ICH and FDA :Expectation
Define risk…
20
RISK = f (severity, probability)
Risk has three components:
•What could go wrong?
•What is the probability of failing to achieve a particular outcome?
•What is the impact of failing to achieve a particular outcome?
Types of risk...
1. Positive risk and negative risk
2. Pure risk and business risk
3. Residual risk
4. Secondary risk
5. Known risk and unknown risk
6. Etc.....
Parameters for “calculating” risks
A picture of the life cycle
Probability Detectability Severity
past today future
Refers to
time
Refers to
Refers to
= Risk Priority Number
x x
22
Impact of risk ?
Individual: Risk is a cognitive and emotional response to expected loss.
Society: Risk is a societal expression of expected harm tempered by expected benefits.
Organizations: Risk is a combination of the probability of occurrence and severity of selected harms.
Technical: Risk is usually based on the expected value of the conditional probability of the event occurring times the consequence of the event given that it has occurred.
Define risk…
Quality Risk Management is Not...
•Hiding risks •Writing half the truth (e.g. in an investigation report) . •A means of removing industry’s obligation to comply with regulatory requirements .
If we do Risk Management properly, we should be able to: • demonstrate that we understand what is important about our business; • have a documented, approved rationale for our decisions; • be proud to share these with regulatory agencies because they demonstrate our knowledge and logical thought processes.
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
Indentify Risk…
Indentify Risk… (Manage quality risks!....)
Quality management as function of time
Co
nse
qu
ence
s
What if
disaster happens?
Nowadays
QR
M
Using QRM
Prior use of QRM may
lower the consequences
25
Indentify Risk…Who is responsible ?
Responsibilities
Teams include experts from the appropriate areas
• Quality unit,
•business development
• engineering
• regulatory affairs
• production operations
• sales and marketing
• legal, statistics and clinical
Decision maker •Take responsibility for coordinating quality risk management across various functions and departments.
• Assure that a quality risk management process is defined, deployed and reviewed and that adequate resources are available.
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.
Measure Risk…
Risk Assessment -It consists of the identification of potential hazards and the analysis and evaluation of risks
(harm) associated with those hazards.
26
Measure Risk
stage Risk assessment
Risk identification Risk analysis
Risk evaluation
Sources of information..
• Manufacturer’s technical, operation and maintenance manuals
• Equipment history cards
• Breakdown data- types, frequency, criticality , downtime etc.
• Quality Problems
• Safety incidents – near misses, accidents
• Qualifications status
.............................. Etc
Measure Risk…
27
Risk identification
Identify possible sources of risk (problems , breakdowns etc.) by asking two basic often
helpful questions:
•What can go wrong?
• What are the possible consequences?
What can go wrong.. FBD example
• Filter bag is damaged.
• Bottom air inlet mesh damaged ,
• Air leaking through base joint.
• Blower stops in between .
• Required temperature not reached .
• Vent joints/pipes developed leaks .
• Blower motor jammed.
• (Mechanical, electrical, instrument & other problems)
.......
Measure Risk…
28
Risk analysis
The estimation of the risk associated with the identified hazards.
•Basically Two factors..
• Severity (S) ----consequences & Level of impact(s)
• Occurrence (O) --- Probability of occurrence
• Risk Score = Severity x Occurrence
• Risk = S x O
Severity & probability ratings..
Qualitative or Quantitative ratings are used to judge the extent of severity and probability of occurrence of the risk.
• Qualitative Severity – Minor , Moderate, Critical etc.
•Probability – high, medium, Low etc.
• Quantitative Rating scales 1-3, 1-5, 1-10 etc.
N.B-Guidelines need to be established for assigning appropriate rating.
Measure Risk…
29
sample copy Risk Assessment work sheet
Potential risk Failure Mode Severity Probability Risk Score
Action plan Owner Due Date
(what can go wrong ) (What can go wrong) (1-10) (10 is (High scores)
List each failure mode 10 is Worst
very probable)
(need attention)
1.Solution
a)
b)
c)
Measure Risk…
30
Risk Evaluation
•Risk scores are used to decide whether the risk is significant and requires
further actions to reduce the level of risk (or otherwise accept and live with it)
• This is done either by analyzing individual risk scores or by preparing “ Risk
Evaluation Matrix”.
• Appropriate control actions are initiated to reduce or handle the risk
(mitigation).
Improve & Analysis….
Basic management facilitation method. (flow chart, check sheets, process mapping ,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
31
Failure Mode Effects Analysis (FMEA)
32
Improve & Analysis….
Improve & Analysis….
Failure Mode Effects Analysis (FMEA) •FMEA generates a living document that can be used to anticipate and prevent failures from occurring.
FMEA is a systematic method to: 1. Recognize, evaluate, and prioritize potential failures and their effects .
2. Identify actions which could eliminate or reduce the chance of potential failure occurring .
3. Document and share the process .
FMEA addresses : •Potential failures of product , process, system or machinery to meet requirements (failure mode) . •Potential consequences (failure effect) . • Potential causes of the failure mode (failure cause) . • Application of current controls . • Level of risk. • Risk reduction (additional controls)
33
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)….. •Types of FMEA
System – Potential failure modes between the functions of the system caused by system deficiencies.
Design – Failure modes caused by system deficiencies. Process – Failure modes caused by process design. Service – Failure modes caused by system or process deficiencies.
34
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
Definition
Failure :A proper function or performance (of product, process, equipment etc.) to meet a
standard; not performing as required or expected.
Failure Mode :The manner of failure . The way in which the product or process could fail to
perform its intended function.
Failure Effects : the consequences of failure. The outcome of the occurrence of the failure
mode on the system, product, or process. Failure effects define the impact on the customer. Ranking is
translated into “Severity” score .
Failure Causes :Potential causes or reasons the failure mode could occur .
•Likelihood of the cause creating the failure mode is translated into an “Occurrence” score
Current Controls .
•Mechanisms currently in place that will detect or prevent the failure mode from occurring .
Ability to detect the failure before it reaches the customer is translated in “Delectability” score.
35
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
When to Use FMEA
1)When a process, product or service is being designed or redesigned.
2) When an existing process, product or service is being applied in a new way.
3) Before developing control plans for a new or modified process.
4) When analyzing failures of an existing process, product or service.
5) Periodically throughout the life of the process, product or service.
36
Concept…A Team Tool • A team approach is necessary.
• Team should be led by the Process Owner who is the responsible manufacturing engineer or technical
person, or other similar individual familiar with FMEA.
The following should be considered for team members:
– formulation development team – Operators
– Process team – Analytical team
– Materials Suppliers – Suppliers
– Customers
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
37
Occurrence Rating Scale
Rating Description Potential Failure Rate 10 Very High: Failure is
almost inevitable.
More than one occurrence per day or a probability of more than three occurrences
in 10 events.
9 High: Failures occur almost
as often as not.
One occurrence every three to four days or a probability of three occurrences in 10
events .
8 High: Repeated failures. One occurrence per week or a probability of 5 occurrences in 100 events .
7 High: Failures occur often. One occurrence every month or one occurrence in 100 events .
6 Moderately High: Frequent
failures.
One occurrence every three months or three occurrences in 1,000 events .
5 Moderate: Occasional
failures.
One occurrence every six months to one year or five occurrences in 10,000 events .
4 Moderately Low:
Infrequent failures.
One occurrence per year or six occurrences in 100,000 events .
3 Low: Relatively few
failures.
One occurrence every one to three years or six occurrences in ten million events .
2 Low: Failures are few and
far between.
One occurrence every three to five years or 2 occurrences in one billion events .
1 Remote: Failure is unlikely. One occurrence in greater than five years or less than two occurrences in one billion
events .
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
38
Severity Rating Scale Rating Description Definition (Severity of Effect)
10 Dangerously high Failure could injure the customer or an employee.
9 Extremely high Failure would create noncompliance with federal regulations.
8 Very high Failure renders the unit inoperable or unfit for use.
7 High Failure causes a high degree of customer dissatisfaction.
6 Moderate Failure results in a subsystem or partial malfunction of the product.
5 Low Failure creates enough of a performance loss to cause the customer to
complain.
4 Very Low Failure can be overcome with modifications to the customer’s process or
product, but there is minor performance loss.
3 Minor Failure would create a minor nuisance to the customer, but the customer can
overcome it without performance loss.
2 Very Minor Failure may not be readily apparent to the customer, but would have minor
effects on the customer’s process or product.
1 None Failure would not be noticeable to the customer and would not affect the
customer’s process or product.
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
39
Detection Rating Scale
Rating Description Definition
10 Absolute Uncertainty The product is not inspected or the defect caused by failure is not detectable.
9 Very Remote Product is sampled, inspected, and released based on Acceptable Quality
Level (AQL) sampling plans.
8 Remote Product is accepted based on no defectives in a sample.
7 Very Low Product is 100% manually inspected in the process.
6 Low Product is 100% manually inspected using go/no-go or other mistake-proofing
gauges.
5 Moderate Some Statistical Process Control (SPC) is used in process and product is final
inspected off-line.
4 Moderately High SPC is used and there is immediate reaction to out-of-control conditions.
3 High An effective SPC program high.
2 Very High All product is 100% automatically inspected.
1 Almost Certain The defect is obvious or there is 100% automatic inspection with regular
calibration and preventive maintenance of the inspection equipment.
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
40
Failure Mode Effects Analysis (FMEA)… Procedure
41
1. For each process input (start with high value inputs), determine the ways in which
the input can go wrong (failure mode)
2. Severity (s) --For each failure mode, determine effects
Select a severity level for each effect ( scaled range 1 to 10 , 10-very serious)
Importance of the effect on customer requirements
3. Occurrence (o) ---Identify potential causes of each failure mode
Select an occurrence level for each cause ( scaled range 1 to 10 , 10-high like wood)
4. Detection (D)---List current controls for each cause.
Select a detection level for each cause. ( scaled range 1 to 10 , 10-canot detect)
The ability of the current control scheme to detect or prevent a given cause
5. Calculate the Risk Priority Number (RPN)= S x O x D
6. Develop recommended actions, assign responsible persons, and take actions
Give priority to high RPNs
MUST look at severities rated a 10
7. Assign the predicted severity, occurrence, and detection levels and compare RPNs
Improve & Analysis….
Improve & Analysis….
42
FMEA
Brainstorming
C&E Matrix
Process Map
Process History
Procedures
Knowledge
Experience
List of actions to prevent
causes or detect failure
modes
History of actions taken
Inputs Outputs
Failure Mode Effects Analysis (FMEA)…
Failure Mode Effects Analysis (FMEA)…
43
Improve & Analysis….
Failure Mode Effects Analysis (FMEA)…
44
Improve & Analysis….
Improve & Analysis….
Failure Mode, Effects and Criticality Analysis (FMECA) Concept… •Failure Mode And Effects Analysis (FMEA ) might be extended to incorporate an investigation of the degree of severity of the consequences, their respective probabilities of occurrence, and their delectability, thereby becoming a Failure Mode Effect and Criticality Analysis . • Failure Modes = Incorrect behavior of a subsystem or component due to a physical or procedural malfunction.
• Effects = Incorrect behavior of the system caused by a failure.
• Criticality = The combined impact of the probability that a failure will occur & severity of its effect .
•Failure Modes effects and Ccriticality Aanalysis (FMECA) = a step-by-step approach for identifying all possible failures in a design, a manufacturing or assembly process, or a product or service .
Significance
•The FMECA facilitates identification of potential design reliability problems
•Identify possible failure modes and their effects
•Determine severity of each failure effect
•FMECA helps
•removing causes of failures
•developing systems that can mitigate the effects of failures.
.to prioritize and focus on high-risk failures
45
Case study ..
46
Case study ..
47
Case study ..
48
Case study ..
49
Case study ..
50
Case study ..
51
Case study ..
52
Case study ..
53
Case study on Risk control
54
Case study on Risk control
55
Case study on sakura tablet (formulation )
56
.
57
case study
.
58
case study
.
59
case study
.
60
case study
.
61
case study
other methodes Improve & Analysis….
Basic management facilitation method. (flow chart, check sheets, process mapping ,etc)
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
62
Improve & Analysis….
Basic management facilitation method.
Process Mapping: Process mapping is a workflow diagram to bring a clearer understanding
of a process or series of parallel processes.
Method-
Flowchart- A flowchart is a picture of the separate steps of a process in sequential order.
When?
• To document a process .
• When planning a risk .
• To communicate to others how a process is done.
• To develop understanding of how a process is done.
63
Improve & Analysis….
Basic management facilitation method…
64
Written Procedures: A written procedure is a step-by-step guide to direct the reader through a task . When?
• process is lengthy and complex
• process is routine, but it's essential that everyone strictly follows rules.
• person wants to know what is going on when a product is being developed.
Benefits:
• Having written procedures prevent mistakes .
• Frees your creativity .
• Procedures saves time .
• Ensures consistency and improves quality .
Work Instruction: Work instructions defines how one or more activities in a procedure should be written in
detail, using technology or other resources .The purpose of a Work Instruction is to organize steps in a logical
format so that an employee can easily follow it independently .
Improve & Analysis….
Fault Tree Analysis (FTA)
What ?
• FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.
When ?
• Root cause analysis of a failure is needed .
Why? - (outcomes)
•A better understanding of the root causes of a failure.
•A better set of action plans to eliminate those root causes .
How to build a Fault Tree
1) Identify a top failure.
2) Brainstorm basic contributors to failure.
3) Link contributors to the top failure
•Determine which combination of contributors is needed to cause the top failure.
(Ask: How many of the inputs are needed to cause the top failure? )
•Link the contributors to the top failure with the correct gate. (And/Or)
Ask: Can we determine contributors for this lower failure ?
Yes - repeat cycle making each contributor a top failure, assign gates, etc...
No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc...
65
Improve & Analysis….
Fault Tree Analysis (FTA)
What ?
• FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.
When ?
• Root cause analysis of a failure is needed .
Why? - (outcomes)
•A better understanding of the root causes of a failure.
•A better set of action plans to eliminate those root causes .
How to build a Fault Tree
1) Identify a top failure.
2) Brainstorm basic contributors to failure.
3) Link contributors to the top failure
•Determine which combination of contributors is needed to cause the top failure.
(Ask: How many of the inputs are needed to cause the top failure? )
•Link the contributors to the top failure with the correct gate. (And/Or)
Ask: Can we determine contributors for this lower failure ?
Yes - repeat cycle making each contributor a top failure, assign gates, etc...
No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc...
66
Fault Tree Analysis (FTA)
Basic symbols: Basic Flow Fault in a box indicates
that it is a result of previous faults FAULT
OR
AND
Connects two or more faults that must occur simultaneously to cause the preceding fault
Connects preceding fault with a subsequent fault that could cause a failure
Improve & Analysis….
Fault Tree Analysis (FTA)..
Basic symbols: End Points & Connector
Root cause (= basic fault)
(e.g. part failure, software error, human error) Root cause
Fault to be further analyzed
with more time or information if needed
Transfer-in and transfer-out events
Improve & Analysis….
Fault Tree Analysis (FTA)..
Additional Symbols Exclusive OR Gate:
Fault occurs
if only one of the input faults occurs
m
Priority AND Gate:
Fault occurs
if all inputs occur in a certain order
Voting OR Gate:
Fault occurs if “m” or more out of “n” input faults
occurs
Improve & Analysis….
Fault Tree Analysis (FTA)
Investigation of laboratory failures
Out of specification
result
Production
Lab error
others
or
outlier
systematic
random
or or
Calibration
Interfaces
other
Improve & Analysis….
Improve & Analysis….
Experiences
•Better as a retrospective tool
•Visually focused: aid for showing linkages
Limitations
•Only as good as input .
•Time and resource consuming (needs FMEA as a complement ).
•Need skilled leader to focus on what is really important
•Need significant amount of information
•Human errors may be difficult to predict
•Many potential fault trees for a system
-Some more useful than others
-Need to evaluate contribution
Improve & Analysis….
72
•HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety & method of identifying and controlling sources of variation at critical process steps that could lead to a hazardous condition.
•Similar to a control plan .
•Cannot be used effectively without manual or automated process control methods, including statistical process control
Uses
•New manufacturing process or equipment .
•To identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination).
Limitations
•Requires excellent process knowledge .
•FMEA should precede HAACP to identify critical hazards/failure modes (A HAACP could be an action to reduce risk in a FMEA) .
•Requires use of more complex statistical tools to be effective (Characterization DOEs, SPC, Capability Matrices) .
Hazard Analysis and Critical Control Points (HACCP)
Improve & Analysis….
73
STEPS ....
•conduct a hazard analysis and identify preventive measures for each step of the process;
•determine the critical control points;
•establish critical limits;
•establish a system to monitor the critical control points;
•establish the corrective action to be taken when monitoring indicates that the critical control points are not
in a state of control;
•establish system to verify that the HACCP system is working effectively;
•establish a record-keeping system.
Hazard Analysis and Critical Control Points (HACCP)
Hazard Critical
Control
Point
Variable
to Control
Target
Value
Acceptable
Limits
Comments Monitoring
and Control
Method
Corrective
Action
Record
Tablet
Breakage
Tablet
Form
Compres-
sion
Force
15kN 13 – 18kN Thickness
and harness
of tablet
Automatic
Density
Measure
Eject
Tablet
On Line
Batch
Record
Improve & Analysis….
74
•A theory that assumes that risk events are caused by deviations from the design or operating intentions.
•Identify potential deviations from normal use .
How to perform? A systematic brainstorming technique for identifying hazards using so-called “guide-words” applied to relevant
parameters: No, More, Other Than, None.
Concept
•Focus team discussions by applying “deviations” to specific nodes .
•Deviations are generated by applying Guidewords to process parameters .
•Examine the process by discussing causes of each deviation
•Identify consequences
•Evaluate risk and safeguards
•Make recommendations, if necessary
•Include all parts of the process.
Potential Areas of Use(s)
1. Manufacturing processes
2. Equipment and facilities
3. Evaluating process safety hazards
4. Primarily as starter of a HACCP
5. Operator error (“use error”)
Hazard Operability Analysis (HAZOP)
other methodes Improve & Analysis….
Basic management facilitation method. (flow chart, check sheets, process mapping ,etc)
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
75
Improve & Analysis….
Basic management facilitation method.
Process Mapping: Process mapping is a workflow diagram to bring a clearer understanding
of a process or series of parallel processes.
Method-
Flowchart- A flowchart is a picture of the separate steps of a process in sequential order.
When?
• To document a process .
• When planning a risk .
• To communicate to others how a process is done.
• To develop understanding of how a process is done.
76
Improve & Analysis….
Basic management facilitation method…
77
Written Procedures: A written procedure is a step-by-step guide to direct the reader through a task . When?
• process is lengthy and complex
• process is routine, but it's essential that everyone strictly follows rules.
• person wants to know what is going on when a product is being developed.
Benefits:
• Having written procedures prevent mistakes .
• Frees your creativity .
• Procedures saves time .
• Ensures consistency and improves quality .
Work Instruction: Work instructions defines how one or more activities in a procedure should be written in
detail, using technology or other resources .The purpose of a Work Instruction is to organize steps in a logical
format so that an employee can easily follow it independently .
Improve & Analysis….
Fault Tree Analysis (FTA)
What ?
• FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.
When ?
• Root cause analysis of a failure is needed .
Why? - (outcomes)
•A better understanding of the root causes of a failure.
•A better set of action plans to eliminate those root causes .
How to build a Fault Tree
1) Identify a top failure.
2) Brainstorm basic contributors to failure.
3) Link contributors to the top failure
•Determine which combination of contributors is needed to cause the top failure.
(Ask: How many of the inputs are needed to cause the top failure? )
•Link the contributors to the top failure with the correct gate. (And/Or)
Ask: Can we determine contributors for this lower failure ?
Yes - repeat cycle making each contributor a top failure, assign gates, etc...
No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc...
78
Improve & Analysis….
Fault Tree Analysis (FTA)
What ?
• FTA represents the sequence and combination of possible events that may lead to a failure mode. Once causes are identified, preventive action can be taken .A structured team analysis of the possible underlying causes of a known equipment failure.
When ?
• Root cause analysis of a failure is needed .
Why? - (outcomes)
•A better understanding of the root causes of a failure.
•A better set of action plans to eliminate those root causes .
How to build a Fault Tree
1) Identify a top failure.
2) Brainstorm basic contributors to failure.
3) Link contributors to the top failure
•Determine which combination of contributors is needed to cause the top failure.
(Ask: How many of the inputs are needed to cause the top failure? )
•Link the contributors to the top failure with the correct gate. (And/Or)
Ask: Can we determine contributors for this lower failure ?
Yes - repeat cycle making each contributor a top failure, assign gates, etc...
No - we are finished - We may also end our fault tree when we reach all indeterminable, basics, or causes which require further research etc...
79
Fault Tree Analysis (FTA)
Basic symbols: Basic Flow Fault in a box indicates
that it is a result of previous faults FAULT
OR
AND
Connects two or more faults that must occur simultaneously to cause the preceding fault
Connects preceding fault with a subsequent fault that could cause a failure
Improve & Analysis….
Fault Tree Analysis (FTA)..
Basic symbols: End Points & Connector
Root cause (= basic fault)
(e.g. part failure, software error, human error) Root cause
Fault to be further analyzed
with more time or information if needed
Transfer-in and transfer-out events
Improve & Analysis….
Fault Tree Analysis (FTA)..
Additional Symbols Exclusive OR Gate:
Fault occurs
if only one of the input faults occurs
m
Priority AND Gate:
Fault occurs
if all inputs occur in a certain order
Voting OR Gate:
Fault occurs if “m” or more out of “n” input faults
occurs
Improve & Analysis….
Fault Tree Analysis (FTA)
Investigation of laboratory failures
Out of specification
result
Production
Lab error
others
or
outlier
systematic
random
or or
Calibration
Interfaces
other
Improve & Analysis….
Improve & Analysis….
Experiences
•Better as a retrospective tool
•Visually focused: aid for showing linkages
Limitations
•Only as good as input .
•Time and resource consuming (needs FMEA as a complement ).
•Need skilled leader to focus on what is really important
•Need significant amount of information
•Human errors may be difficult to predict
•Many potential fault trees for a system
-Some more useful than others
-Need to evaluate contribution
Improve & Analysis….
85
•HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety & method of identifying and controlling sources of variation at critical process steps that could lead to a hazardous condition.
•Similar to a control plan .
•Cannot be used effectively without manual or automated process control methods, including statistical process control
Uses
•New manufacturing process or equipment .
•To identify and manage risks associated with physical, chemical and biological hazards (including microbiological contamination).
Limitations
•Requires excellent process knowledge .
•FMEA should precede HAACP to identify critical hazards/failure modes (A HAACP could be an action to reduce risk in a FMEA) .
•Requires use of more complex statistical tools to be effective (Characterization DOEs, SPC, Capability Matrices) .
Hazard Analysis and Critical Control Points (HACCP)
Improve & Analysis….
86
STEPS ....
•conduct a hazard analysis and identify preventive measures for each step of the process;
•determine the critical control points;
•establish critical limits;
•establish a system to monitor the critical control points;
•establish the corrective action to be taken when monitoring indicates that the critical control points are not
in a state of control;
•establish system to verify that the HACCP system is working effectively;
•establish a record-keeping system.
Hazard Analysis and Critical Control Points (HACCP)
Hazard Critical
Control
Point
Variable
to Control
Target
Value
Acceptable
Limits
Comments Monitoring
and Control
Method
Corrective
Action
Record
Tablet
Breakage
Tablet
Form
Compres-
sion
Force
15kN 13 – 18kN Thickness
and harness
of tablet
Automatic
Density
Measure
Eject
Tablet
On Line
Batch
Record
Improve & Analysis….
87
•A theory that assumes that risk events are caused by deviations from the design or operating intentions.
•Identify potential deviations from normal use .
How to perform? A systematic brainstorming technique for identifying hazards using so-called “guide-words” applied to relevant
parameters: No, More, Other Than, None.
Concept
•Focus team discussions by applying “deviations” to specific nodes .
•Deviations are generated by applying Guidewords to process parameters .
•Examine the process by discussing causes of each deviation
•Identify consequences
•Evaluate risk and safeguards
•Make recommendations, if necessary
•Include all parts of the process.
Potential Areas of Use(s)
1. Manufacturing processes
2. Equipment and facilities
3. Evaluating process safety hazards
4. Primarily as starter of a HACCP
5. Operator error (“use error”)
Hazard Operability Analysis (HAZOP)
Improve & Analysis….
88
Hazard Operability Analysis (HAZOP)
Deviation Causes Consequences Safeguards Recommend
High
temperature in
blender
Steam heating
control
malfunction
Feed material #1
reaches
decomposition
temperature
Violent reaction with
toxic gas generation
Personnel exposure/
injury
Equipment damage
Diverse high temp.
interlock on blender
Blender vented
Test interlock
on quarterly
basis
Add steam
heating control
to monthly PM
Limitations of the model
•Applies to specific situations only .
•May need to use other models for quantifying risk .
•Not a structured approach .
•Not designed for quantifiable risk assessment .
•Complex output.
Improve & Analysis….
89
Preliminary Hazard Analysis (PHA)
Preliminary hazard analysis (PHA) is a semi-quantitative analysis that is performed to:
1. Identify all potential hazards and accidental events that may lead to an accident .
2. Rank the identified accidental events according to their severity .
3. Identify required hazard controls and follow-up actions .
The PHA shall consider:
1) The identification of the possibilities that the risk event happens.
2) The qualitative evaluation of the extent of possible injury or damage to health that could result and
3) A relative ranking of the hazard using a combination of severity and likelihood of occurrence, and
4) The identification of possible remedial measures.
Improve & Analysis….
90
Preliminary Hazard Analysis (PHA)
Preliminary Hazard Analysis (PHA)
Hazard Investigation/
Controls Sev Freq
Imp
(SxF)
Potential Areas
• PHA might be useful when analyzing existing systems or prioritizing hazards
where circumstances prevent a more extensive technique from being used.
• It can be used for product, process and facility design as well as to evaluate the
types of hazards for the general product type, then the product class, and finally the
specific product.
Improve & Analysis….
91
Risk Ranking and Filtering
•Risk ranking and filtering is a tool for comparing and ranking risks.
•Risk ranking of complex systems typically requires evaluation of multiple diverse quantitative
and qualitative factors for each risk .
•The tool involves breaking down a basic risk question into as many components as needed to
capture factors involved in the risk.
•These factors are combined into a single relative risk score that can then be used for ranking
risks.
Usage : Risk Ranking and Filtering
• Is most suited to compare and manage a “portfolio” of complex risks .
•Is facilitated through careful breakdown of a risk into constituent risk scenarios.
Low
Medium
High
Severity
Pro
ba
bil
ity
Hig
h
Lo
w
Me
diu
m
Risk Class ONE
Risk Class TWO
Risk Class THREE
Risk Ranking
Risk ranking and filtering
Risk Matrix (1)
Improve & Analysis….
THREE
TWO
ONE
Detection
Ris
k C
lassif
ica
tio
n
Hig
h
Lo
w
Me
diu
m
HIGH priority
MEDIUM priority
LOW priority
Risk Filtering
Risk Matrix (2)
Risk ranking and filtering
Improve & Analysis….
Improve & Analysis….
94
Supporting Statistical Tools
•Control Charts, for example:
a. Acceptance Control Charts
b. Control Charts with Arithmetic Average and Warning Limits
c. Cumulative Sum Charts
d. Weighted Moving Average.
• Design of Experiments (DOE);
• Histograms;
• Pareto Charts;
• Process Capability Analysis.
Control…….
95
Risk control
•The purpose of risk control is to reduce the risk to an acceptable level .
• Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control.
•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
• 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.
Objectives
•Reduce, control or eliminate the risk.
• Design away the risk
•Take action to reduce severity & probability, or improve detectability of hazard.
Control…….
96
Risk acceptance
• Decision to accept risk.
•Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified.
•Risk communication
•sharing information regarding information of risk between decision maker and others.
•Risk Review
•A mechanism to review or monitor events should be implemented.
•After risk control in place, carry out new risk assessment to establish potential failures .
•Determine whether any new hazards may have been created. hazards may have been created.
•Review events that may impact the original decision .
Control…….
97
Root Cause Analysis (RCA )
OBJECIVE ..
•A structured investigation that aims to identify the true cause of a problem, and the actions necessary to eliminate it.
• structured process that uncovers the physical, human, and latent causes of any undesirable event in the workplace.
•Process to Discover
•what happened
• WHY IT HAPPENED
• How it can be prevented focus is on understanding , not blaming
•Analyses CAUSE & EFFECT Relationships
• Emphasis is on SOLUTIONS and System IMPROVEMENT
Types of cause
•Direct Cause: The cause that directly resulted in the event. (The first cause in the chain.)
• Contributing Cause: The cause(s) that contributed to an event but, by itself, would not have caused the event (The cause after the direct cause.)
• Root Cause: The fundamental reason for an event, which if corrected, would prevent recurrence. (Last cause in the chain.)
Control…….
98
Root Cause Analysis (RCA )
Methods
1. Cause Effect Diagram (fish bone)
2. Why Why Analysis
Opportunity for the Industry & Regulators
Using the same guideline apply QRM to Industry (development, manufacture and distribution)
Competent authorities (reviewer and inspectorate)
Facilitates common approaches to quality risk management in our every day jobs
Supports science-based decision making
Focus resources based on risks to patients
Avoids restrictive and unnecessary requirements
Facilitates communication and transparency
Opportunities & Benefits
Encourages transparency Create baseline for more science-based decisions
Facilitates communication Matrix team approach An aid to convince the stakeholders with trust
Encourages a preventive approach Proactive control of risks and uncertainty Benefit of knowledge transfer by team approach
Changes behavior Better understanding of risk-based decisions Acceptance of residual risks
Potential Applications
101
•Development;
•Facility, equipment and utilities;
•Materials management;
•Production;
•Laboratory control and stability testing;
•Packaging and labeling.
•Inspection and assessment activities.
•Regulatory Operations
•Etc.....
102
Next Steps?
From great ideas to practice—how?
Both industry and regulators want to know
Which risks firsts?
Which tools are best?
How will I know “good” from “bad” risk management?
Do we need dept./divisions of risk managers?
103