WELCOME TO GMP TRAINING SESSION

GMP TRAINING – SYMED LABS

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QUALITY RISK MANAGEMENT

BY:V.J.V.PRASAD, MANAGER-QA

GMP TRAINING

GMP TRAINING – SYMED LABS

GMP TRAINING – SYMED LABS

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OBJECTIVES

To provide information on the backgroundof the ICH Q9 document

Give an aid by providing some points of discussions on the understanding of the quality risk management concept

Illustrations of how Risk Management can be applied Pharmaceutical Industry

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PREAMBLE

Risk: A situation involving exposure to danger E.g.: Driving with out wearing helmet

Accident: An unfortunate incident that happens unexpectedly and unintentionally, typically resulting in damage or injury

Risk Management: A systematic process for the assessment, control, communication and review of risks.

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Former methods for Quality Risk Management

Methods of risk management in earlier days:

Trends review Check lists Maps Flow Charts Compilation of observations

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Potential areas for Risk Management application

Documentation [SOPs, Batch records etc.] Training [Schedules and effectiveness] Quality defects [Complaints, deviations, OOS etc.] Audits [Compliance] Periodic reviews [Revalidation assessment] Change controls [Impact assessment] Facilities, Equipment and Utilities [Components, maintenance ] Material management [Receipt, storage and distribution] Packaging and labeling [Container closure system and

labeling]

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Approaches to Quality Risk Management

In general we are using two approaches to manage the risks ...

Pro active: Identify the treat exposure areas to mitigate the potential for loss, before the loss occurs.

E.g.: Analysis before implementation.

Reactive: Investigate the treat exposure areas to identify the potential source for loss and its control, after the loss occurs.

E.g.: Failure investigations.

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Area of scope for Risk Management

Process

Materials

Design

Manufacturing

Distribution

Patient

Facilities

Area for Opportunities to manage the risk

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Risk Based Concepts by ‘ICH’

“risk-based”

concepts and principles

Q8Q9

Q10 Q11

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Risk Based Concepts by ‘ICH’ R

isk

from

Man

ufa

ctu

rin

g

site

High

Low

HighLow

Using Q9 Quality

Risk Manageme

nt principles

Q10 P

harm

. Q

ualit

y S

yst

em

s

Q8 Pharmaceutical Development

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METHODS FOR RISK ASSESSMENT

Qualitative: The ‘What’ analysis Quantitative: The ‘How much’

analysis

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Severity and Probability are simple concepts?

Which consequence is more severe?

300 lives lost in single, fiery plane crash. 300 lives lost on roads over a weekend. 300 lives potentially lost from cancer within the next 20 years

Which probability is probable?

What does a “30% chance of rain tomorrow” mean? 30% of the days like tomorrow will have at least a trace of rain. 30% of the area will have rain tomorrow. 30% of the time tomorrow, it will rain.

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Parameters for evaluating the ‘Risk’…

severity

pro

babili

ty

high

medium

low

dete

ctab

ility

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Estimation of Risk through RPN..?

Probability (P) Detectability (D) Severity (S)

Refe

rs to

Refe

rs to

Refe

rs to

Risk Priority Number = P X D X S

x x

past today future time

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Calculation of Risk Priority Number….

Low=1 Moderate=2 High=3

Risk Priority Number (RPN) = P X D X S

RPN Scale:

Rating scale for Risk:

Low: 0 to 9 Moderate: 10 to 18 High: 19 to 27

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Over view of typical QRM process…

Risk Review

Ris

k C

o mm

unic

atio

n

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

anagement tools

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Basic Risk Management Tools…

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);

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Failure Mode Effect Analysis (FMEA) concept…

FMEA provides for an evaluation of potential failure modes for processes and their likely effect on outcomes and/or product performance. Once failure modes are established, risk reduction can be used to eliminate, contain, reduce or control the potential failures. FMEA relies on product and process understanding. FMEA methodically breaks down the analysis of complex processes into manageable steps. It is a powerful tool for summarizing the important modes of failure, factors causing these failures and the likely effects of these failures.

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Failure Mode Effect Analysis (FMEA) Process….

Identify an area where risk exists. Describe the system and function Create a block or process flow diagram indicating

relationships within the process Create a worksheet containing information about the

system (related block diagram) What is important is that you have a process to

analyze potential failure modes (i.e. problems that could happen) AND the potential effects of that failure on your process.

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STEP #1: Selecting the High Risk Process

Examples of how you can do this: Lengthy process with more stages. High risk of failures in the process. Top failed product in the history. Processes that are heavily dependent on

human intervention. Product manufacturing in the oldest facility. Process/Facility with rapid changes.

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STEP #2: Forming the assessment team

The assessment team should be Subject matter expert. Cross functional. To cover all levels. Solid understanding to the process being

assessed. Well experienced on the process being assessed. Well qualified with strong analytical skills.

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STEP #3: Diagram the process

Map the process with flow charting Clearly define the process with simple steps. Don’t skip the critical steps during mapping. Determine how things intended to work Vs. how

thing actually working. Consult the experts to determine the best

practices for the process. Allow team to the work site to observe the process

steps before mapping of process diagram.

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STEP #4: Identify the potential failure modes

Process can have multiple failure modes and each failure mode can have multiple effects.

Address the following questions during failure modes identification. What could fail with this step? (Failure modes) Why would this failure occur? (Causes) What could happen if failure occurs? (Effects)

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STEP #5: Assess the failure modes and Causes

Risk mitigation requires an understanding of the Severity, probability and detestability of the exposure.

Use clear scale for rating of risk consistently. Keep the scales simple and ensure they are

appropriate to the exposure and organizations risk tolerance.

Causes identification should be transparent to mitigate the risk effectively.

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STEP #6: Assessment of critical failure modes

The highest RPN’s should be focused on first and should be considered as critical.

Ask the following questions during assessment

What might cause the failure to occur? When might the failure occur? Where might the failure occur? Why might the failure occur?

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STEP #7: Redesign the process

Considerations for the redesignation of the process. If identified the critical failure mode. If inadequate controls are exists. If existing process not robust.

Direct the redesignated process prior to its wide spread implementation.

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Frame work for Failure Mode Effect Analysis

Assesses the steps of the process and identify where the problems may occur.

Identify consequences of each failure mode should it occur.

Scores the exposures quantifiably. The highest RPN’s should be focused on first. Assists with better understanding of the process. Brain storming is the critical to the process.

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Concerns regarding QRM implementation

Hiding risks Writing half the truth (e.g. in an

investigation report) A means of removing industry’s obligation

to comply with regulatory requirements Both Companies & Inspectors have to think

and not simply follow black and white rules

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Conclusions for ICH Q9

Over all: Positive Contribution to patient protection Further develops Quality Risk Management awareness,

that is already part of industry and regulatory culture

Ongoing change in behaviour Identifying risks can be positive A long list of identified risks that are assessed and

controlled provides high quality capability Awareness of quality risks

“Risk-based approach” A potential of risks remains - No “Zero” risk!

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Change in behavior….

From tick-box approach for compliance

Towards systematic risk-based thinking

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Conclusion

The weakest link in the

chain will no longer.... be a

problem. The use of Quality Risk Management is mandatory is an expectation of EU & PICs GMP

However, if you don’t use it,

you will not gain the benefits

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QUESTIONS ???

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THANK YOU

GMP TRAINING – SYMED LABS