Mootaz+el halawany+view+to+risk+management

17/10/15 Mootaz El Halawani 1

My perspective toRisk Management


Example: FDA’s Inspection Risk-based Approach

• Sept. ’04 - Risk-based Method for Prioritizing CGMP Inspections

• FDA convened a panel of experts

• Brainstorming sessions identified 70 potential risk factors!


•SCOPE:•New Project

•Processes•Systems and Utilities

•Equipment


Scheme

Team approach

Risk Review

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Risk Assessment

Risk Evaluationunacceptable

Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

InitiateQuality Risk Management Process

Output / Result of theQuality Risk Management Process

Risk M

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ICH Q9


Risk Team:

Chaired by the technical sector director, all technical department managers and who could attend and be responsible to review, analyze, and approve CAPA

Risk Owner:

Represented by the process owner who is responsible for initiating, reporting risk, conducting its activity and implementation of CAPA


Tools for Risk Management

IDENTIFY:• Cause-&-Effect

Analysis (Fish bone)

2. Process Mapping / Flowcharts

ASSESS

1. Brainstorming

2. 5 WHYS?

EVALUATE/MITIGATE

1. FMEA (+RPN)

Other tools:• QFD• FTA• FMECA• HACCP

• Decision Trees• Etc.


Process FlowS t a r t / E n d P r o c e s s

P r o c e s s S u b r o u t i n e s

D e c i s i o n P o i n t

P r o c e s s A l t e r n a t e P r o c e s s

M a n u a l O p e r a t i o n

P r o c e s s

D e l a y

D e c i s i o nP o i n t

O f f - p a g e P r o c e s s

S t a r t / E n d P r o c e s s

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Example: Cause-and-Effect Diagram for the elements of

process validation

Vessel #1

MACHINERY

ENVIRONMENT

MEASUREMENT

METH

ODO

LOGY

MATERIA

LS

MANPO

WER

Approved APIs

Approved Excipients

Approved PKG & LBLQC

Pharm Eningeering

Operations

Mfg

.

Pkg.

Validation Policies

Validation SOPs

Validation Approach

Mat

rix

3 Bat

ches

Manufacturing

Packaging

Filling

Labeling

Minor

Major

MBR

PROT

Surfaces

Air

Controlled Access

Gowning

PPE

VMP

In Process

Volume

Spec.Density

Release

StabilityAnalytical

Micro

Analyt

ical

Micro

Humidity

Temp.

Changes/

Hr.

Water

Purifie

dWFI

Vessel #2


Example: Brainstorming how do we clean equipment & facilities?

AutomatedSystem

(Not in-place)

SIP System

Manually

CIP System

Combinationof methods

How do weclean it?

No productresidue

No detergentresidue

No micro-organisms

No dye orflavor

residues

What are the criteriafor clean?

RISK:CLEANING

VALIDATION

Equipment

Facilities

Handtools

IMTE

What needs tobe cleaned? Supppliers

QA

QC Labs

Operations

Who is involved?(Functionally)


5 WHYS?????


Imagine!

Risk ManagementQuality Risk Management

Quality SystemsHarm

SeverityStakeholder

Product Life CycleGMP Compliance


Principles of Quality Risk Management

Two primary principles:

The evaluation of the risk to quality should be based on scientific

knowledge (without preaching the guidelines!!!) and ultimately link to the protection of the patient

The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk

ICH Q9


Should risksbe assessed?

Are there clear rulesfor decision making?

e.g. regulations

Yes“no RM“

Risk assessment not required(No flexibility)

Follow procedures(e.g. Standard Operating Procedures)

Document results,decisions and actions

When to apply Quality Risk Management?

CONSIDERATIONS

Based on K. Connelly, AstraZeneca, 2005

1. What might go wrong?2. What is the likelihood (probability) it will go wrong?3. What are the consequences (severity)?No or

justification needed

Can you answerthe risk assessment

questions?

Yes“informal RM“

Initiate Risk assessment(risk identification, analysis & evaluation)

Run risk control(select appropriate measures)

Agree on a team(small project)

Select a Risk Management tool(if appropriate e.g. see ICH Q9 Annex I)

No“formal RM“

Carry out thequality risk management process

Document the steps


The Process Flow

A Risk Acceptance

process1/3

Risk Review

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Risk Assessment


Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

Initiate QualityRisk Management Process

Output / Result of the QualityRisk Management Process

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EXAMPLE

Finish baseline forrisk acceptance decisionrisk identification, risk analysis,risks evaluation, risks reduction

Risk reduction stepfinished

Yes

Stakeholdersinvolved as appropiate?

Revisitrisk assessment step

All identifiedrisks assessed?

No

Yes

No


Risk Review

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Risk Assessment


Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance



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EXAMPLE

Evaluate measureson severity, probability, detectability

Check needed resourcese.g. employee, money

Measures / Actionsappropriate?

No

Yes

Revisitrisk reduction step

Other hazardscaused?

Yes

Is a riskreducible?

No

Measures/actions needed?

Yes

No

17/10/15 Mootaz El Halawani 18Risk Review

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Risk Assessment


Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance



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EXAMPLE

Accept theresidual risk?

Ready for communication

Accept riskSign off documentation

Is a riskreducible?

Yes

Advantageoutweighs risk?

Yes No

Yes

No

Risk not acceptableSign off documentation

Revisitrisk assessment step

No


Quality risk management

Industryoperation - Submissions- Manufacturing

Regulatorsoperation

- Reviews- Inspections

Communicationfacilitates trust

and understanding

CONSIDERATIONS

17/10/15 Mootaz El Halawani 20QUALITY SYSTEM

ICH Q9Quality Risk Management

PRINCIPLES PATIENT PROTECTIONEFFORT

PR

OC

ES

S

ASSESSMENT

CO

NT

RO

L

COMMUNICATION

IDENTIFICATION

ANALYSIS

EVALUATION

REDUCTION

ACCEPTANCE

REVIEW EVENTS

ACCEPT (RESIDUAL RISK)

INTERDISCIPLINARY

TEAMS

WHAT`?PROBABILITYSEVERITY

CRITERIA

Failure Mode, Effects & Criticality Analysis

TOOLS

INFORMAL

HACCPHAZOP

FMEA

FMECA

FTA

PHA

Hazard Analysis & Critical Control Points

Preliminary Hazard Analysis

Fault Tree Analysis

Failure Mode Effect Analysis

Hazard Operatibility Analysis

QUALITY Mgt.

INDUSTRY

REGULATORY

DOCUMENTATION

TRAINING

AUDITING

CHANGE CONTROL

MATERIALS

PRODUCTIONQU

INSPECTION

ASSESSMENT

APPLICATION

RISK

PROBABILITY OF HARMSEVERITY

CAUSE OF DAMAGE

CAUSE OF HARM

HA

ZAR

D

Peter Gough, Stephan Roenninger, ICH Q9 : Quality Risk Management - an update Regulatory Affairs Journal, 16, 2005, 91-93

Bill Paulson, ICH Q9 Provides ImplementationFramework for Quality Risk Management

Gold Sheet, 39, May 2005

© J. Arce, F. Hoffmann-La Roche


RPN

Risk Assessment: Risk Evaluation

A picture of the life cycle Probability Detectability Severity

past today futureD

ata refers to

time

Impac t

Can y ou fin d

it?

= Risk Priority Number

x x

• Frequency of “occurences” driven by the number of trials• Degree of belief

CONSIDERATIONS


Assign Levels of Probability of Hazard Occurrence

Probability

This means the Hazard

)3(Is very likely to occur , more than one time / year

)2(Will Probably occur, one time/ year

)1( Accidental event ,exceptional occurrenceMay occur some time , Infrequently, one time /more than one year


Assign Hazards Severity LevelsSeverity This means the hazard

)3( Possible impact on the manufactured product

and with possible hazard for the patient (end

user)

)2( Possible impact on the manufactured product

but without risk for the patient (end user)

)1( Addressed by applicable GMP, OR without

possible impact on the manufactured product


Assign Detection ControlDetection This means the Hazard

)3( Absence of system of detection but

detection is still possible by chance

)2( Presence of a single system of detection

which is not 100% reliable

)1( System of multiple and independent

detection tools or a single system of

detection which is 100% reliable


3- Numerical risk evaluation (RPN value (:

Multiplication product of severity, frequency and delectability for example:


•Risk degree assessment and the equivalent action taken as follows:

RPN

value

Risk

factor

Action taken

1-6 MinorAccepted

8-12 Major

To be registered in risk register and closed through 40 working days

unless any other justification

18-27 Critical

To be registered in risk register and closed through 30 working days

unless any other justification


EXAMPLE

Mootaz+el halawany+view+to+risk+management

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