Equipment Risk Management

A Quality Systems Approach

Palash Chandra Das

 Agenda
• Brief Introduction
• Correlation between Quantitate and
qualitative approach
• Implementation and assessment
• Discussion with practical example

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 What is Quality
• The degree to which a set of inherent
properties of a product, system or process
fulfills requirements. (ICH Q9)

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 So what is the concept of Risk
Assessment?

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 Risk

• Anything that
may cause harm

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 Overview of a typical quality risk
management process

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 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)?

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 Risk identification
• 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.

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 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.

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 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.

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 Risk control
Risk 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?

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 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.

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 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.

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Risk communication

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 Risk review

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 Life cycle of Risk Program

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 Risk Assessment is embed into Quality
Management System

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 Sub-components
• Design
• Control system
• Components
• Safety
• Measuring instrument
• Document
• Process
• Computerized system controls

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

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 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

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 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

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 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

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

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

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 Computerized system controls (1/2)
• User should auto reset password in case of periodic password expiry without
intervention from admin.
• Availability of auto lockout facility, if the system is idle more than 2 min
• Minimum availability of three level of user
• Defined user privilege matrix, need to be provide from vendor with DQ/FDS.
• Software/application backup/restore CD
• Data backup compatibility connected through LAN
• Password history. E.g. should not accept recent 3 password
• In case of back up data review, all Audit trail, cycle data / reports, Alarm should be
in readable non editable format e.g. PDF

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 Computerized system controls (2/2)
• Auto password expiry, setting need to be enable by admin privilege
• Date & time change, parameter setting, data deletion or transfer privileges, exit
application should to under administrator only.
• Date and Time synchronization with organization network time server
• For SCADA based system , application should to be boot with system start up. Exit
application option only enable with admin.
• The Installed SCADA application should support the periodic antivirus scan.
• OEM and Plant admin should to be clearly identified in authorization list.
• Availability of user manuals , preventive manual and electronic diagram and P&ID
should to be available in soft format e.g. PDF format
• Remote service should be enable for SCADA applications for maintenance/up
gradation by the OEM. E.g. Team Viewer application

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 Qualitative approach

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 Qualitative risk ranking

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 FMEA model

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 Relationship of CQA, CPP, and Critical Aspects

Critical Process step need to be

relook to evaluate the impact

Identify all Critical Aspects

whichever directly or indirectly
impacting your process step

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 Example: Compounding or Filtration vessel
System Sub Risk Justification Mitigation
components
Vessel Agitator Agitator Mixing may • To control the speed, agitator
not not be shall be provided with VFD
working uniformed with indicator
properly • 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
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Example: De-pyrogenation Tunnel
System Sub Risk Justification Mitigation
components
Conveyor Over If Filling M/C is • Inter lock in between
Loading stopped vial filling and tunnel shall be
of will checked during OQ
conveyor accumulate in
to the
conveyor
Tunnel
Conveyor Speed Improper heat • VFD shall be provided
variability distribution with VFD with indicator
and • Conveyor speed shall be
penetration verify
during routine
operation

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 Example: Filling M/C
System Sub Risk Justification Mitigation
components
Filling Nitrogen Oxidation Nitrogen Gas • Nitrogen flow shall be
M/C purging after flow controlled by flow meter
filling reduces or • Alarm shall be indicated
stops at for low pressure by
purging station machine

Filling Load cell Filling Load cell • Operation range shall be

M/C rejects malfunctioning verified
• Routine calibration policy
need to be establish
• PM procedure
• SOP shall be prepared
and training shall be
imparted

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 Example: LAF Bench
System Sub Risk Justification Mitigation
components
Blower Vibration Sample may Anti vibration pads /
In work fall on other mechanism
bench bench due to shall be provided to
vibration avoid vibration.

LAF Blower Blower Continuous • The ON/OFF switch shall

Bench efficiency running of be provided for
reduce the blower controlling the blower
shall cause operation.
lot of power • LED indicators for the
loss and may motor operation shall be
damage the provided.
blower.

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 Example: MCDP

System Sub Risk Justification Mitigation

components
MCDP Temperature Temperature Controller not • Controller challenge
controller of steam get activate test shall be
goes down whenever steam performed during
temperature falls OQ/OQ.
below the set
limit.
Steam Delay in Due to • Steam pressure valve
pressure valve distillation insufficient shall be provided and
steam supply Controllers shall be
Multicolumn challenge in OQ
efficiency may be
decrease

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 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).

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 Author
Palash Chandra Das
M. Pharma
LinkedIn Link
Pharmaceutical Chemistry
Core Technical Area: Qualification &
Validation , Sterility Assurance, QMS, Risk
Management

Palash Chandra Das is the Technical Writer focuses on technical writing including investigative reports and
operating procedures. His passion for writing is displayed in the many writing sessions he hosts via his
Blogs at https://pres.net.in.

Mr. Palash Chandra Das is recognized as an expert in the field of aseptic manufacturing of parenteral
products, and is a frequent presenter at several web conferences and technical training for Sterile Drug
Manufacturing.

He earned his Master’s for Pharmaceutical chemistry from the University of West Bengal University of
technology in India.

Since 2011 Palash has associated with installation, qualification and operation several production-lines in
standard Clean room Technology as well as in Isolator Technology at major regulatory facility across India.

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 Visit Us:
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4/15/2018
Thank You
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