workshop on risk assesment by palash ch das

www.uscgmp.com by Palash Ch Das

Quality Risk Management

ByPalash Chandra Daswww.uscgmp.com (official blog)

http://www.uscgmp.com/




Quality Risk Management Brief Introduction Correlation between Quantitate and

qualitative approach Implementation and assessment Discussion with practical example


What is Quality The degree to which a set of inherent

properties of a product, system or process fulfills requirements. (ICH Q9)


Overview of a typical quality risk management process


Risk Assessment

As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful:1. What might go wrong?2. What is the likelihood (probability) it will go wrong?3. What are the consequences (severity)?


Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description.

Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders.

Risk identification addresses the “What might go wrong?” question, including identifying the possible consequences.

Risk identification


Risk analysis Risk analysis is the estimation of the

risk associated with the identified hazards.

It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms.

In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.


Risk evaluation

Risk evaluation compares the identified and analyzed risk against given risk criteria.

Risk evaluations consider the strength of evidence for all three of the fundamental questions.


Risk controlRisk control includes decision making to reduce and/or accept risks. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort used for risk control should be proportional to the significance of the risk. 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 Risk reduction focuses on processes for

mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level (see Fig. 1).

Risk reduction might include actions taken to mitigate the severity and probability of harm.

Processes that improve the detectability of hazards and quality risks might also be used as part of a risk control strategy.

The implementation of risk reduction measures can introduce new risks into the system or increase the significance of other existing risks.


Risk acceptance

Risk acceptance is a 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.

For some types of harms, even the best quality risk management practices might not entirely eliminate risk.

In these circumstances, it might be agreed that an appropriate quality risk management strategy has been applied and that quality risk is reduced to a specified (acceptable) level.

This (specified) acceptable level will depend on many parameters and should be decided on a case-by-case basis.


Risk communication


Risk review


Life cycle of Risk Program


Sub-components

Design Control system Components Safety Measuring instrument Document Process


Design

Capacity e.g. Blower, Motor, Condenser, Exhaust, refrigerator etc.

Insufficient Space e.g. shelf /chamber size/work bench

Cleanability e.g. CIP or Manual Loading /Unloading e.g. Door

movement/ auto loading and unloading/ manual handling

Proper illuminations


Control System

Access level verification Process automation/semi automatic Human machine Interface Data backup Online Monitor/record Printed data


Components MOC Verification e.g. 316L or 304 Surface roughness e.g. internal mirror surface finish ≤0.5

µm Ra and external surface finish < 1.2µm Ra, matte finish. Wed joints e.g. All welds shall be ground finished to ≤1.2

µm Ra and properly passivated and orbital welding should be done

joints with triclover joints e.g. Gaskets e.g. shall be high temperature & pressure resistant

and O-rings coming in direct / indirect contact surfaces shall be made up of food grade polymeric materials only.

Filter and filter housing e.g. Porosity and certificates Proper tagging of components e.g. for identification as

per P&ID Lubricant e.g. Food grade certificate shall be provided for

lubricant


Safety Electricity e.g. Equipment should start with

human intervention only. After regain of power the equipment should start from the step it stopped.

Control system e.g. Machine should stop with alarm.

Notifications e.g. Various utilities supply should be interlocked and indicated by alarm.

Noise level e.g. Noise level shall be below 75 dB at a distance of 1 m from the equipment.

Moving part wiring e.g. All moving parts & wiring to be covered, Proper earthlings of the equipment


Measuring Instrument

Appropriate range e.g. Operational range of measuring instruments > instrument working range, appropriate accuracy, Mounting of instruments must give the possibility for dismounting and replacement, easy access for calibration

Calibration e.g. traceable to national or international standards


Documents

Component certificates Operation manual Maintenance manual SOP for cleaning and operation Training to relevant Preventive maintenance


Process impact

Evaluate how Controls are impacting the output Operational verification Performance verification Procedural Implementation Review the validated state Preventive maintenance Breakdown handling


Qualitative approach


Qualitative risk ranking


FMEA model


Example: Compounding or Filtration vesselSyste

mSub

components

Risk Justification

Mitigation

Vessel Agitator Agitator not working properly

Mixing may not be uniformed

• To control the speed, agitator shall be provided with VFD with indicator• Alarm will generated if

motor is tripped • The RPM beyond the

set limit shall notify the operator with alarm and shut down the process.• Agitator performance

(RPM) and controller shall be verified during OQ and requalification• PM procedure shall be

implement


Example: Filling M/CSyste

mSub

components

Risk Justification

Mitigation

Filling M/C

Nitrogenpurging

Oxidation after filling

Nitrogen Gas flowreduces or stops atpurging station

• Nitrogen flow shall be controlled by flow meter

• Alarm shall be indicated for low pressure by machine

Filling M/C

Load cell Filling rejects

Load cell malfunctioning

• Operation range shall be verified

• Routine calibration policy need to be establish

• PM procedure • SOP shall be

prepared and training shall be imparted


Example: De-pyrogenation Tunnel Syste

mSub

components

Risk Justification

Mitigation

Tunnel

Conveyor Over Loading of conveyor

If Filling M/C is stopped vial will accumulate in to the conveyor

• Inter lock in between filling and tunnel shall be checked during OQ

Conveyor Speed variability

Improper heat distribution and penetration during routine operation

• VFD shall be provided with VFD with indicator

• Conveyor speed shall be verify


Example: LAF BenchSyste

mSub

components

Risk Justification

Mitigation

LAF Bench

Blower VibrationIn work bench

Sample may fall onbench due tovibration

Anti vibration pads /other mechanismshall be provided toavoid vibration.

Blower Blower efficiency reduce

Continuousrunning ofthe blowershall causelot of powerloss and maydamage theblower.

• The ON/OFF switch shall be provided for controlling the blower operation.

• LED indicators for the motor operation shall be provided.


Example: MCDP

System

Sub componen

ts

Risk Justification Mitigation

MCDP Temperature controller

Temperature of steam goes down

Controller not get activate whenever steam temperature falls below the set limit.

• Controller challenge test shall be performed during OQ/OQ.

Steam pressure valve

Delay in distillation

Due to insufficientsteam supply Multicolumn efficiency may bedecrease

• Steam pressure valve shall be provided and Controllers shall be challenge in OQ

Risk mapping For Process


Initiate Process Map Review process steps 9 times(e.g. Personnel,

Process, Equipment failure, Facility/utility) Identify the process GAP’s or Risk ranking

(e.g. Training, Supplier quality, audit, review validation and process SOP)

Communicate the risk Buildup the process control Reduce the risk Revisit the risk for review


Process flow Manufacturing


Process Mapping


Reference ICH Q9 PDA TR 44 PIC/S Quality Risk Management PS/INF 1/2010 Annex 2, WHO TR 981 EudraLex The rules governing medicinal products in the

European Union, Vol. 4. Good manufacturing practice (GMP) guidelines (http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm).


Thank You

workshop on risk assesment by palash ch das

Health & Medicine