Concept to risk management ( In context to Q9)

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


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.

http://www.webster.com/dictionary/determine

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



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.


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


Risk Assessment

Risk Control

Risk Review

Risk Identification

Risk Analysis

Risk Evaluation

Risk Reduction

Risk Acceptance

Review Events

Output / Result of the


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


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



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


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


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



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



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 .



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.



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.



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



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



43



44



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

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http://en.wikipedia.org/wiki/Failure_mode_and_effects_analysis




Case study ..

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Case study ..

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Case study ..

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Case study ..

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Case study ..

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Case study ..

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Case study ..

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Case study on Risk control

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Case study on Risk control

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Case study on sakura tablet (formulation )

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.

57

case study

.

58

case study

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59

case study

.

60

case study

.

61

case study

other methodes Improve & Analysis….








62


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


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 .



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



What ?


When ?


Why? - (outcomes)













66


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


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



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



Investigation of laboratory failures

Out of specification

result

Production

Lab error

others

or

outlier

systematic

random

or or

Calibration

Interfaces

other



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


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) .



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 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


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”)


other methodes Improve & Analysis….








75


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


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 .



What ?


When ?


Why? - (outcomes)













78



What ?


When ?


Why? - (outcomes)













79


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



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



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



Investigation of laboratory failures

Out of specification

result

Production

Lab error

others

or

outlier

systematic

random

or or

Calibration

Interfaces

other



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


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) .



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 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


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”)



88


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.


89


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.


90



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.


91


•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)


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



94


•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

Concept to risk management ( In context to Q9)

Technology

risk decision

terminology risk

risk of life

estimated risk

risk communication

risk management approach

risk management decisions

risk assessment analysis