Quality Risk Management

Tony Gould
 Introduction

Risk management is not new we do it informally

all the time
Military Standard 1629 dated 1974 regarding
formal risk management
Risk management has been used in the medical
device, telecommunications, aerospace and car
industries for many years

2 | PQ Workshop, Abu Dhabi | October 2010

 Introduction

Risk management has also been part of the pharma

industry for many years:
GMP requirements are designed to address risk. For example,
the specific GMP requirements for sterile products are designed
to mitigate the risk of sterility failure
In some cases, GMP specifies a risk based approach. For
example, "a risk assessment approach should be used to
determine the scope and extent of validation required" (WHO
Annex 4, 5.2.10)
Specifications in pharmacopoeial monographs include tests for
known potential contaminants

3 | PQ Workshop, Abu Dhabi | October 2010

 Introduction

Greater use of risk management tools in the future

We must accept this and prepare
From a GMP point of view, we are only concerned
with risks associated with quality, safety and
efficacy quality risk management
Organisations use risk approaches in other areas,
e.g. to ensure resources are utilised in the most
effective way. Also applicable to inspectorates

4 | PQ Workshop, Abu Dhabi | October 2010

 GMP requirement

A system for quality risk management should be included

in the quality assurance system
Quality risk management is a systematic process for the
assessment, control, communication and review of risks
to the quality of the medicinal product. It can be applied
both proactively and retrospectively.
The quality risk management system should ensure that:
the evaluation of the risk to quality is based on scientific
knowledge, experience with the process and ultimately links to
the protection of the patient; and
the level of effort, formality and documentation of the quality
isk management process is commensurate with the level of
risk.
1.2 1.5

5 | PQ Workshop, Abu Dhabi | October 2010

 QRM - the dangers

There is a desired outcome and risk management

is used to justify it
Invalid assumptions suit the desired outcome
Cost reduction (increased profits) is often the real
reason that many risk assessments are done
Cost reduction may be a secondary outcome
Variable tolerance of risk

6 | PQ Workshop, Abu Dhabi | October 2010

QRM from an inspectors point of view

Be prepared so that the process is understood

Have sufficient knowledge to understand what has
been done and challenge assumptions, omissions
etc
Be clear about when QRM is not appropriate
Be flexible and accept the outcome of a
scientifically sound QRM exercise
If done properly there should be increased
assurance of quality (and possibly cost savings)

7 | PQ Workshop, Abu Dhabi | October 2010

 What is QRM

"Quality Risk Management is a systematic process

for the assessment, control, communication
and review of risks to the quality of the medicinal
product across the product lifecycle." (ICH Q9)

8 | PQ Workshop, Abu Dhabi | October 2010

 Typical QRM process
Initiate
Quality Risk Management Process

Risk Assessment
What might go wrong or
Risk Identification

has gone wrong?

Risk Analysis

Risk Evaluation
What is likelihood or
unacceptable
probability?

Risk Management tools

Risk Communication

Risk Control

Risk Reduction What are the

Risk Acceptance consequences (severity)?
Output / Result of the
Quality Risk Management Process
What is the level of risk?
Risk Review
Any mitigating factors?
Review Events

9 | PQ Workshop, Abu Dhabi | October 2010

 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." (ICH Q9)

10 | PQ Workshop, Abu Dhabi | October 2010

 Risk assessment terms

Risk identification
Use of information to identify hazards or potential risks
Historical data, theoretical analysis, informed opinions
Risk analysis
Estimation of risk associated with identified hazards
Qualitative or quantitative
Links probability and severity
In some tools, includes detectability

11 | PQ Workshop, Abu Dhabi | October 2010

 Risk analysis - probability

A simple qualitative tool:

P Probability of Occurrence
High Likely to occur

Medium May occur

Low Unlikely to occur

Remote Very unlikely to occur

12 | PQ Workshop, Abu Dhabi | October 2010

 Risk analysis - severity

A simple qualitative tool:

S severity level if event occurs

Serious GMP non-compliance
Critical
Patient injury possible
Significant GMP non-compliance
Moderate
Impact on patient possible
Minor GMP non-compliance
Minor
No patient impact

13 | PQ Workshop, Abu Dhabi | October 2010

 Risk assessment terms

Risk evaluation
Compares identified and analysed risk against criteria
Considers probability, severity and detectability
Output can be qualitative (high, medium or low)
Output can be quantitative (probability x severity x
detectability)
Quantitative provides a relative ranking prioritises
risk

14 | PQ Workshop, Abu Dhabi | October 2010

 Risk evaluation

A simple risk table with risk acceptability criteria:

Risk = P x S
Severity
Minor Moderate Critical
Probability
Unacceptable risk Intolerable risk Intolerable risk
High
Acceptable risk Unacceptable risk Intolerable risk
Medium
Acceptable risk Acceptable risk Unacceptable risk
Low
Remote Acceptable risk Acceptable risk Acceptable risk

15 | PQ Workshop, Abu Dhabi | October 2010

 Risk evaluation

Modify evaluated risk according to existing

detection controls
Detectability:
High the control is likely to detect the negative event
or its effects
Medium the control may detect the negative event
or its effects
Low the control is not likely to detect the negative
event or its effects
Zero no detection control in place

16 | PQ Workshop, Abu Dhabi | October 2010

 Risk evaluation

Risk definitions:

Intolerable work to eliminate the negative event or

introduce detection controls is required as a priority
Unacceptable work to reduce the risk or control the
risk to an acceptable level is required
Acceptable the risk is acceptable and no risk
reduction or detection controls are required

17 | PQ Workshop, Abu Dhabi | October 2010

 Risk control

"Actions implementing risk management

decisions" (ICH Q9)
Includes risk reduction (if applicable) and risk
acceptance

18 | PQ Workshop, Abu Dhabi | October 2010

 Risk control terms

Risk reduction
Actions taken to lessen the probability of occurrence
of harm and the severity of that harm
Typically CAPA and change control
Risk acceptance
The decision to accept risk
If risk reduction action taken, follows re-analysis and
evaluation

19 | PQ Workshop, Abu Dhabi | October 2010

 Risk Review

"Review or monitoring of output/results of the risk

management process considering (if appropriate)
new knowledge and experience about the risk."
(ICH Q9)
Ensures nothing has changed to affect the QRM
assumptions, output and conclusions
Consider during product review

20 | PQ Workshop, Abu Dhabi | October 2010

 QRM tools some of them!

Basic risk management facilitation methods (flowcharts, check

sheets 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.

21 | PQ Workshop, Abu Dhabi | October 2010

 Potential applications

Quality Management (e.g. self-inspection, training, complaints,

deviations, change control)
Development (ICH Q8)
Facilities, Equipment and Utilities (e.g. design, qualification,
hygiene, calibration, computers)
Materials Management (e.g. supplier assessment, storage)
Production (e.g. validation, in-process sampling and testing)
Laboratory Control and Stability Studies (e.g. OOS, retest
periods, validation)
Packaging and Labelling (e.g. package design, label control)

22 | PQ Workshop, Abu Dhabi | October 2010