22 Jul 2022

QUALITY
RISK MANAGEMENT
OUTLI N E
Definition
Principle and Methods
Tools and Purposes
QRM Application
Benefit of QRM Programme
DEFINITION

Damage to health, including the damage

that can occur from loss of product quality
or availability

The potential source of harm

The probability of occurance of harm and

severity of that harm
HAZARD HARM RISK

Water Drowning Jumping in without

knowing how to swim

Gasoline Explosion Lighting a match

Driving Car accident Texting

WHA T I S
R ISK MANAGE MENT

Control Mitigate

Allows efficient and

Is a continuous process
for the identification,
economical applicant of
Risk Assessment is the Analyse Monitor
resources to areas that
evaluation, prioritisation, process that use for
require control in order
control and evaluating risks
to minimise unwanted
communication of risks
outcomes Identify Report

QUALITY RISK MANAGEMENT

A SYSTEMATIC process for the

.... of RISK to the QUALITY of the DRUG PRODUCT

.... across the product LIFECYCLE

Evaluation of the risk to quality should be based on scientific knowledge

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
Why QRM Matters

When GMP fails.....public confidence is damaged

Death
Shortages
ICH Q10 Pharmaceutical quality system (PQS)
Product Life Cycle Stage Goals

Pharmaceutical development Technology transfer Commercial manufacturing Product discontinuation

Investigational products GMP

Management Responbilities

Process performance & Product Quality Monitoring System

PQS elements for
Corrective / Preventive Action (CAPA) System
continual improvment of process
Change Management System
performance and product quality Management Review

Knowledge Management
Enablers
Quality Risk Management
KEY POINTS
FOR SUCCESSFUL RISK ASSESSMENT

Risk assessment to be performed for a

precise subject in a define context

Team working
Risk assesment
Perform Risk assesments by using an appropriate
tool
Suitable for objectives

Effort commensurate to the level of risk to be assessed

Initiate Quality Risk Management What might go wrong?
Process
What when wrong?

Risk Assessment

Risk Identification

Risk Analysis
Qualitative/ Quantitave
process -->
Risk Evaluation likelihood of occurence and

Risk Management Tools

Risk Communication

Unnacceptable
severity of harm
Risk Control
Risk Reduction

Calculated risk
Risk Acceptance
criteria
Output / Result of the Quality Risk
Management Process
Output should be
Risk Review periodically monitored and
Review Event
reviewed based on new
Quality Risk Management Model knowledge &experience
ICH Q9, PIC/S & EU GMP Annex 20
Initiate Quality Risk Management Follow-up of the action plan
Process

Risk Assessment Risk control steps to include:

Risk Identification
Define Risk control measures, Action plans
Risk Analysis
with the team
Risk Evaluation Structure action plans according to risk

Risk Management Tools

Risk Communication

Unnacceptable

prioritization
Risk Control
Risk Reduction
Risk communication
Risk Acceptance
Risk assesment
Risk acceptance criteria
Output / Result of the Quality Risk Risk control measures-action plans
Management Process
Checking, follow-up of the action
Risk Review plans
Review Event
DOCUMENTATION
To formally document the quality risk management
performed

...to accumulate experiences

QRM TOOLS AND PURPOSES
Identification and gathering information of all
potential involved factors (proactive) or causes of
problems (reactive) in the rist assesment

Appropriate tools
Which is the appropriate tool?
TOOLS AND PURPOSES:
1. Basic risk management facilitation methods : 1. Fault Tree Analysis (FTA)
2. Hazard and Operability
Brainstorming
(HAZOP)
3. Preliminary Hazard Analysis (PHA)
Process flow diagram, Process mapping
4. Hazard Analysis and
Critical Control Points (HACCP)
Checksheet
5. Failure Mode Effect Analysis
(FMEA)
Flow chart 6. Failure Mode Effect Critical
Analysis (FMECA)
Fishbone Diagram 7. Risk Ranking & Filtering
8. Supporting statistical tools
TOOLS AND PURPOSES:

FMEA: Failure mode effect analysis

Objective: To evaluate process to identify

1 Review the process.
potential failure modes for processes, their
2 Brainstorm potential
failure modes.
likely effects on outcomes and criticality
4 Once failure modes are established, risk
3
Assign Severity
Rankings.

5
List potential

Assign Occurrence
effects of failure. reduction can be used to eliminate, contain,
Rankings
reduce or control the potential failures

7 Calculate the RPNs 6 Assign Detection

Rankings. Method: FMEA methodically breaks down the
analysis of complex processes into
8 Develop the Action
Plan.
10 Calculate the
resulting RPNs. manageable steps. It is a powerful tool for
summarizing the important modes of failure,
9 Take action
factors causing these failures and the likely
effects of these failures.
Initiate Quality Risk Management
Process

Risk Assessment Risk Assessment : Risk Identification

Risk Identification

Risk Analysis Risk Assessment : 3 basic question

1. What might go wrong ?
Risk Evaluation 2. What is likelihood it will go wrong

Risk Management Tools

Risk Communication

Unnacceptable 3. What will happen if it goes wrong

Risk Control
Risk Reduction Risk Identification
Addressed questions "What might go wrong?"
Risk Acceptance
Determine by historical data, knowledge of stakeholders etc

Output / Result of the Quality Risk

Management Process

Risk Review
Review Event
Risk Assessment : Risk Analysis

Initiate Quality Risk Management

Process
Is the estimation of risk
It considers :
- Severity of harm
Risk Assessment
- Likelihood of occurrence
Risk Identification - In some tools, the ability to detect the harm
It is qualitative or quantitative
Risk Analysis

For Quantitative
Risk Evaluation Criteria Qualitative

Risk Management Tools

Risk Communication

Unnacceptable
1 2 3 4 5

Risk Control Minor

Severity (S) Major Least Severe Extremely Severe
Risk Reduction Critical
Severity
Risk Acceptance 1 2 3 4 5
Minor
Likelihoof of
Major
Output / Result of the Quality Risk Occurence (P) Critical Remotely Possible Extremely Possible
Management Process Occurance

Minor 1 2 3 4 5
Risk Review
Detection (D) Major
Review Event Critical Very High Extremely Low
Detectability
Risk Assessment : Risk Evaluation
Initiate Quality Risk Management
Quantitative Qualitative Action to be taken
Process

RPN ≤ 8 or each value for severity,

Minor No action
probability and detectability ≤ 2
Risk Assessment

Risk Identification RPN > 8 dan ≤ 27 or each value for Action needed to reduce risk
severity, probability and detectability Major (mitigation) or scientific
Risk Analysis > 2 dan ≤ 3 rationale for acceptance

RPN > 27 or each value for severity, Action needed to reduce risk

Risk Management Tools

Risk Evaluation Critical
Risk Communication

Unnacceptable
probability and detectability > 3 (mitigation)

Risk Control Risk Risk

Risk Identification Risk Assessment
Evaluation Control
Risk Reduction
Pro R Risk
Potential Potential Current Risk
Risk Acceptance cess S P D P Cate
Failure Causes Control Decision
Step N gory

Output / Result of the Quality Risk Penggunaan

Management Process ceklis
penerimaan
Ketidak Dokumen
Peneri saat Tidak
sesuaian dari
maan melakukan emerlukan
Risk Review antara CoA supplier 1 2 3 6 Minor
Materi pengecekan mitigasi
dan Surat Jalan tidak
Review Event al kelengkapan risiko
Supplier  sesuai
dan
kesesuaian
dokumen
Risk Assessment : Risk Evaluation

Iterative process

Risk Assessment Risk Risk

Risk Identification Evaluation Control

R R
Process Potential Risk Risk
Potential Failure Current Control S P D P S P D P
Step Causes Category Decision
N N

Penggunaan
ceklis penerimaan Tidak
Ketidak Dokumen
saat melakukan memer
sesuaian dari
Penerimaan Material pengecekan 1 2 3 6 Minor lukan

antara CoA dan Surat supplier

kelengkapan dan mitigasi
Jalan Supplier  tidak sesuai
kesesuaian risiko
dokumen
Initiate Quality Risk Management Post Risk Acceptance, Risk Review & Communication:
Process

Evaluate the Critical & Major risks again after

Risk Assessment
implementation of actions (Post mitigation)
Risk Identification

Risk Analysis
Minor Major Critical
Risk Evaluation

Risk Management Tools

Risk Communication

Unnacceptable

Risk Control No further action

Risk Reduction needed
Mitigation Actions
Risk Acceptance

Complete
Output / Result of the Quality Risk
Management Process

Is iterative
Risk Review
Reviewed periodically on
Review Event
receipt of new information
Quality Risk Management

Proactive Reactive

Without occurence of any failure One after failure

Manage the risks associated with Facilitate a risk-based assessment

process effectiveness and Justify risk-based decisions
product quality Specify and implement risk management
measures
QUALITY RISK MANAGEMENT APPLICATION

Risk Assessment & Risk Management incorporated into all areas of

a pharmaceutical operation

1 Integrated Quality Management Development

Product designing-QbD
2
Documentation Periodic Review
Traininng & Qualification Enhance product knowledge
Change Manegement m
Quality Defect Evaluate CMA
Continual
Quaity Auditing Establishing specification, manuf control
Improvement
Decrease variability

3 Facility, Utility & Equipment Production Material Management 5

Design facility/equipment Validation
In process sampling & testing (evaluate and Starting material
Cleaning & environmental control
justify the use of process analytical Use of material
Calibration & PM (determine the scope and
technologies (PAT) in conjunction and real Storage & Logistic Conditions
extent of qualification)
Computer system & computer- controlled
equipment
time release
4
6 Laboratory Control & Stability Studies Packaging & Labelling
7
OOS Design of packages
Retest/expiration dating Selection of container/closure
Label control

Annexure II of ICH Q9
Benefit of a QRM Programme

Risk Assessment are LIVING DOCUMENTS

Deviations/investigations/changes
When a new risk assessmnet has been performed--> mitigation actions should
be reviewed with other risk assessment
Risk Management can be used for Knowledge Management
Detailed process flow
Information regarding what detail is required in SOPs

Risk Management saves time and resources

Reduces process downtime
Reduces resources & effort required --> non value added activities
DONT

Just put in Quality manual or SOP!

Hiding risks

Justifying poor quality of product and / or processes

NEVER USE RISK MANAGEMENT TO JUSTIFY BAD MANUFACTURING PRACTICE!!