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Risk considerations for the installation of a new pharmaceutical facility

autoclave

Article · March 2018

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Risk considerations for the installation of a new
pharmaceutical facility autoclave
TIM SANDLE
ABSTRACT: This article considers some of the risk considerations that need to be accounted for
when replacing a steam sterilization autoclave within a pharmaceutical processing facility. In outlining the
key risk considerations, the article adopts a risk assessment approach – Failure Modes and Effects Analysis
(FMEA).
KEYWORDS:
Risk assessment, risk control, risk review, risk communication, failure modes, effects analysis, steam
sterilization, engineering systems,cross comparison, risk management, autoclaving, autoclave.
This is an edited extract from the book "Risk
Assessment and Management for Healthcare
Manufacturing: Practical Tips and Case
Studies" by Tim Sandle, available from the
PDA Bookstore at:
https://store.pda.org/ProductCatalog/Product.a
spx?ID=3329
Introduction
This article considers some of the risk
considerations that need to be accounted for
when replacing a steam sterilization autoclave
within a pharmaceutical processing facility. In
outlining the key risk considerations, the article
adopts a risk assessment approach – Failure
Modes and Effects Analysis (FMEA).
An autoclave is a pressure chamber used to
sterilize equipment and supplies by subjecting
them to high pressure saturated steam
(Sandle, 2013). Autoclaves are used within
pharmaceutical facilities to eliminate microbial
cells and spores from within a given device.
Autoclaves commonly use steam heated to
115–134°C (250 273°F). To achieve sterility, a
holding time of at least 30 minutes at 115°C,
15 minutes at 121°C (250°F) or 3 minutes at
134°C (273°F) is required (Hugo, 1991).
The validation and verification of the
sterilization process is well monitored in the
pharmaceutical industry and operators must
ensure that autoclaves comply with various
guidance and regulations. Nonetheless, the
purchase of a new autoclave and the
assessment requires evaluation. An additional
dimension is added when one autoclave is
being used to replace another, as with the
case study discussed here. To make such an
evaluation, a formal risk assessment is
required under the auspice of quality risk
management.
Risk management and risk assessment
principles should be applied as early as
possible during the design and construction of
steam sterilization devices. With steam
sterilization devices the most critical functions
are, arguably, the steam sterilization of direct
and indirect the product contact parts. A
second important aspect relates to air removal.
All of the trapped air must be removed from
the autoclave before activation. This is
because trapped air is a very poor medium for
achieving sterility
Formal risk approaches normally share four
basic concepts, which are listed below:
1) Risk assessment;
2) Risk control;
3) Risk review;
4) Risk communication.
This article considers the application of FMEA.
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Failure Modes and Effects Analysis (FMEA)
Risk management is fundamentally about
understanding what is most important for the
control of equipment or design quality and then
focusing resources on managing and
controlling these aspects to ensure that risks
are reduced and contained. Risks relate to a
situation, event or scenario where a
recognized hazard may result in harm. Before
risks can be managed they need to be
assessed (Sandle, 2011).
Risk assessment involves identifying risk
scenarios. In relation to cleanroom and clean
air design this should ideally be a prospective
exercise rather than in reaction to a failure.
This process involves determining what can go
wrong in the system and all the associated
consequences and likelihoods. To achieve
this, some kind of risk assessment tool is
required (Sandle and Lamba, 2012).
In ICH Q9 three key definitions are outlined
(ICH, 2009). These help to contextualize what
is meant by 'risks':
• Risk: The combination of the
probability of occurrence of harm and
the severity of that harm,
• Harm: Damage to health, including the
damage that can occur from loss of
product quality or availability,
• Hazard: The potential source of harm.
For engineering systems, one of the most
widely used tools is Failure Modes and Effects
Analysis (FMEA) (Sandle, 2006).
FMEA, as discussed at various stages in this
book, is a highly structured approach and can
be undertaken through the following steps:
a) Setting the scope;
b) Defining the problem;
c) Setting scales for factors of severity,
occurrence and detection (see below);
d) Process mapping;
e) Defining failure modes;
f) Listing the potential effects of each
failure mode;
g) Assigning severity ratings to each
process step;
h) Listing potential causes of each failure
mode;
i) Assigning and occurrence rating for
each failure mode;
j) Examining current controls;
k) Examining mechanisms for detection;
l) Calculating the risk;
m) Examining outcomes and proposing
actions to minimize risks.
Starting the risk assessment process
Before commencing a risk assessment it is
important to define the size and the scope of
the assessment (remaining focused on what is
to be achieved); to select the appropriate team
(often an interdisciplinary team is best);
selecting and reviewing the appropriate risk
management tool; deciding upon any
numerical scale to be used and prioritizing the
different problems to be addressed.
These steps can be broke down thus:
• Gathering data through an audit and
analysis;
• Constructing diagrams of work flows;
• Pin-pointing areas of greatest risk;
• Examining potential sources of
contamination;
• Deciding on the most appropriate
sample methods;
• Helping to establish alert and action
levels;
• Taking into account changes to the
work process / seasonal activities;
• Using some type of scoring system so
that the risk can be ranked and the
level of risk determined.
In doing so the following questions should be
asked:
• What is the function of the equipment?
How are its performance
requirements?
• How can it fail to fulfill these functions?
• What can cause each failure?
• What happens when each failure
occurs?
• How much does each failure matter?
What are its consequences?
• What can be done to predict or
prevent each failure?
• What should be done if a suitable
proactive task cannot be found?
These reflective questions help to structure the
risk assessment activity.
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Risk criteria
As part of the risk assessment exercise it is
important to establish the risk assessment
criteria. This is necessary in order to place
risks in proportion to one another and against
a universal scale. Without this, it cannot be
determined whether one risk is a greater or
lesser problem compared with another or if a
given risk could potentially result in patient
harm.
With FMEA either a numerical scoring system
can used or marker phrases, such as ‘high’,
‘medium’ or ‘low’ can be deployed. In this case
study, marker terms are used. These terms
are applied to three aspects. These are the
severity of the hazard; how likely the hazard is
to occur; and whether there are any
mechanisms in place to detect the hazard
should it occur. Here:
• Severity is the consequence of a
failure, should it occur;
• Occurrence is the likelihood of the
failure happening (based on past
experience);
• Detection is based on the monitoring
systems in place and on how likely a
failure can be detected. Sometimes, a
good detection system is described as
one that can detect a failure before it
occurs.
When these three are cross-compared, the
overall risk can be established. The best
means to do this is through the use of risk
Risk Classification and Risk Filtering
Record the risk classification based upon the impact and likelihood from the table (Table 1). This is
established through the use of a filter (or matrix).
Table 1: Classification of risk
CLASSIFICATION OF RISK
Impact Likelihood
Low
Low LOW
Medium LOW
High MEDIUM
filters (these are illustrated in Tables 1 and 2
below).
Before looking at the risk filter tables, it is
necessary to define each of the terms used to
establish the overall risk.
Severity of Impact
• High = Patients safety will be impacted
• Medium = Potential patient safety
issues
• Low = No impact on patient
Likelihood of Occurrence
• High = 1 failure per year
• Medium = 1 failure every 5 years
• Low = 1 failure every 10 years
For Documentation the likelihood is as follows:
• High = No Documentation
• Medium = Incorrect Documentation
• Low = Documentation present and
correct
Probability of Detection
• Low = Will not be detected by in-place
systems
• Medium = Only one mechanism for
detection by existing systems
• High = More than one mechanism for
detection by existing systems
Medium High
LOW MEDIUM
MEDIUM HIGH
HIGH HIGH
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Risk Priority
Record the risk priority based upon the risk classification and probability of detection from the table.
Table 2: Risk priority
RISK PRIORITY
Probability Of Detection
Risk Classification
High
Low LOW
Medium LOW
High MEDIUM
Risk process
In formulating the risk assessment a group
was assembled consisting of engineering,
validation, microbiology and the end-users.
The process began by identifying the key risk
factors and potential failure modes. These
were described as “functional details.” Once
these were defined, these primary categories
were broken down into sub-steps (termed
“sub-functional details.”
Once these were selected and agreed, the
steps were grouped together. The group then
proceeded to assess the risk for each step,
using the FMEA schema outlined above. This
consisted of:
a) Considering the relevance of each
sub-functional detail (for example,
whether it could potentially impact
upon product quality).
b) The possible risk scenarios were
considered.
c) The severity of impact was then
assessed as either “high”, “medium” or
“low”, using the definitions outlined
above.
d) The likelihood of impact was then
assessed, using the same descriptors.
e) With the severity and likelihood
assessed, the risk class was
determined using Table 1 (above).
f) The probability of detection was
assessed next.
g) Knowing the probability of detection
allowed the overall risk priority to be
determined (using Table 2 above).
h) The penultimate step was to consider
whether any controls or risk mitigation
factors were in place.
i) The final step was to reach a
conclusion in relation to risk
management.
Medium Low
LOW MEDIUM
MEDIUM HIGH
HIGH HIGH
The risk assessment process is outlined in
Appendix I. In terms of an example:
Equipment preparation
With equipment loading, an important sub-
functional detail is with equipment loading. The
relevance of loading an autoclave incorrectly is
an impact on product quality. Here the risk
scenario is an incorrect sterilization of the load.
In this case:
a) The severity of impact would be high;
b) The likelihood of impact could be
medium.
This produces, according to Table 1, a high
risk class.
The probability of detection would be low,
because the activity is operator dependent and
there are no system aspects that prevent an
incorrect load from being prepared. Therefore,
using Table 2, the risk priority is high.
However, in terms of risk mitigation and risk
management, a clear SOP can be put in place
and operators can be trained in order to lower
the possibility of an incorrect load being
prepared. In addition:
• Photos of the loads can be prepared
(during the Operational Qualification).
• Schematics to be included in the SOP.
• Worst-case loads can be verified
during both the Operational
Qualification and Performance
Qualification.
This example is included in Appendix I. Other
sub-functional steps were derived using similar
processes.
Downloaded from www.sterilize.it 4
Risk example
Appendix I contains an example of a
replacement autoclave. The table is arranged
in a fashion to facilitate the risk assessment
steps described above, where functional and
sub-functional steps are outlined. The case
study was designed around a particular device
and should be regarded as illustrative. Users
embarking on a similar process should take
note of the items covered; however, they
should construct their own risk schematic and
reach conclusions that are relevant to their
own particular circumstances. Some
abbreviations are used in the table; these are
defined in a glossary at the end .
Conclusion
The final assessment was that the new
autoclave can be fitted and that the risks are
adequately controlled. It was noted that
although the new autoclave has a newer
control systems technology the steam
sterilization principles together with the load/
test cycles remain in line with the autoclave
that is being replaced.
The methodology selected – FMEA – was
appropriate to the task. An alternative
approach could have been to use a numerical
risk assessment. However, the use of
descriptor words like “high”, “medium” and
“low” proved adequate in relation to the
activity.
References
Hugo WB (1991). A brief history of heat and
chemical preservation and disinfection. J.
Appl. Bacteriol. 71 (1): 9–18
ICH Q9: Quality risk management.
International Conference on Harmonization of
Technical Requirements for Registration of
Pharmaceuticals for Human Use ICH, Geneva
(November 2005)
Sandle, T. (2003). The use of a risk
assessment in the pharmaceutical industry –
the application of FMEA to a sterility testing
isolator: a case study, European Journal of
Parenteral and Pharmaceutical Sciences; 8(2):
43-49
Sandle, T. (2011): Risk Management in
Pharmaceutical Microbiology. In Saghee,
M.R., Sandle, T. and Tidswell, E.C. (Eds.)
(2011): Microbiology and Sterility Assurance in
Pharmaceuticals and Medical Devices, New
Delhi: Business Horizons, pp553-588
Sandle, T. (2013). Sterility, Sterilisation and
Sterility Assurance for Pharmaceuticals:
Technology, Validation and Current
Regulations, Woodhead Publishing Ltd.:
Cambridge, UK, pp93-110
Sandle, T. and Lamba, S. S. (2012) Effectively
Incorporating Quality Risk Management into
Quality Systems. In Saghee, M.R. Achieving
Quality and Compliance Excellence in
Pharmaceuticals: A Master Class GMP Guide,
New Delhi: Business Horizons, pp89-12
Downloaded from www.sterilize.it 5
Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Incorrect Documentation
Equipment Autoclave cGMP documentation High Medium High High Medium SAT check during
Operation And supplied IQ.
Maintenance No Documentation
Equipment Manuals cGMP documentation High Medium High High Medium SAT check during
supplied IQ.
Documentation
Drawings not review and
Equipment Drawings And Functional
cGMP the latest High Medium High High Medium approval of
Schematics Specification
revision Functional
(Including
Specification.
P&ID and
Documentation
General
review and
Equipment Assembly No drawings Functional
cGMP High Medium High High Medium approval of
drawings) supplied Specification
Functional
Specification.
Poor Design and Equipment
construction. inspection
Equipment cGMP Components not High Medium High High Medium SAT during
securely commissioning
Equipment installed & IQ checks.
Inspection Equipment
Poor
inspection
construction.
Equipment cGMP High Medium High High Medium during
Components
commissioning
damaged
& IQ checks.

Downloaded from www.sterilize.it 6

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Documentation
Manufacture not check to
performed confirm that
Equipment SAT
Equipment cGMP according to a High Low Medium High Low manufacturing
Inspection
recognized according to
standard BS5750 or
equivalent.
To be created/
Standard
Control SAT/ Approved post
Operating cGMP SOP not in place High Low Medium High Low
System Training supplier
Procedures
training.
Standard Supplier/
Control SOP followed
Operating cGMP High Low Medium Medium Medium Training Training and
System incorrectly
Procedures SOP sign off.
Maintenance Asset
Equipment cGMP requirements not High Low Medium High Low Asset register Registration
Maintenance identified Form
Programme Maintenance Asset
Equipment cGMP procedure not High Low Medium High Low Asset register Registration
produced Form
Equipment
Equipment Logbook not
Operations cGMP High Low Medium High Low SOP Registration and
Logbook present
Assessment
Equipment
Incorrect
Operations cGMP High Medium High High Medium SOP Registration and
labeling
Equipment Assessment
Identification Asset Number
Operations cGMP No identification High Medium High High Medium SOP check during
IQ.
Spare Parts Documentation
Spare Parts List
Operations And Business Critical High Low Medium Medium Medium SOP check during
not available
Consumables IQ.

Downloaded from www.sterilize.it 7

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Consumables Equipment
Operations Business Critical not identified so High Low Medium Medium Medium SOP Registration and
not in stock Assessment
Documentation
Materials not
Equipment cGMP High Low Medium High Low SAT check during
Materials In suitable
IQ.
Product
Documentation
Contact Documentation
Equipment cGMP High Low Medium High Low SAT check during
not available
IQ.
Incorrect Documentation
Equipment cGMP lubricants High Low Medium High Low SAT check during
supplied IQ.
Lubricants
Lubricants not Documentation
Equipment cGMP pharmaceutical High Low Medium High Low SAT check during
grade IQ.
Documentation
Filters not
High Low Medium High Low SAT check during
available
IQ.
Documentation
Equipment Filters Business Critical
check during
Incorrect filters
High Low Medium High Low SAT IQ. Engineering
supplied
Stores to stock
critical filters.
Documentation
Control Incorrect
and Hardware
Equipment System cGMP components High Low Medium High Low SAT
check during
Hardware supplied
IQ.
Documentation
Control Incorrect version
and Software
Equipment System Business Critical of the software High Low Medium High Low SAT
check during
Software supplied
IQ.

Downloaded from www.sterilize.it 8

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Documentation
and Hardware
EPROM failure High Low Medium High Low SAT
check during
IQ.
Control No software Back up disk
Equipment System Business Critical backup disk Medium Low Low High Low SAT check during
Software supplied IQ.
Back up battery
Monitoring Battery checked
Equipment cGMP failure in Chart Medium Low Low High Low SAT
System during IQ.
Recorder
Plant room
Plant room too temperature to
hot for be controlled
Environmental Preliminary
Operations Business Critical Autoclave High Low Medium High Low via extraction
Requirements works
control system and additional
to operate. cooling if
necessary.
Material type
Autoclave sheds
Equipment compliance
dust/ particles
Equipment Generated cGMP High Low Medium High Low SAT certs to be
into clean
Particles checked during
rooms.
IQ.
The utilities
supplied do not The critical
Utilities to be
Utility allow utilities will be
Operations cGMP High Low Medium High Low tested IQ/
Requirements sterilisation designed to be
SAT
conditions to be tested at SAT.
achieved.
Services to be
Services are not
Utility checked during
Operations cGMP satisfactorily High Low Medium High Low SAT
Requirements commissioning
connected
and SAT.

Downloaded from www.sterilize.it 9

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Autoclave
Operating To be checked
Operating
Equipment cGMP Specifications High Low Medium High Low SAT and documented
Specifications
are set-up during OQ
incorrectly
Maintenance
work on the
steam, water or
Tests must be
piped gas
Maintenance repeated before
Operations cGMP services is Medium Low Low High Low SAT
works commissioning
performed after
starts.
installation/
operational tests
are completed
Identification
Critical and
Calibration SAT/
Equipment cGMP instruments not High Low Low High Low classification of
Information SOP
identified instruments
during IQ
Identification
Critical and
Critical SAT/
Operations cGMP instruments not High Low Low High Low classification of
Instruments SOP
calibrated instruments
during IQ
Documentation
Calibration check during
Critical SAT/
Operations cGMP Certificates not Medium Low Low High Low IQ. Calibration
Instruments SOP
available schedule
updated.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Calibration
Documentation
Critical Laboratory not SAT/
Operations cGMP Medium Low Low High Low check during
Instruments traceable to SOP
IQ.
UKAS
Autoclave
Supplier
Training to be
completed on
Supplier
Operators not site post
Operations Training cGMP High Medium High High Medium Training/
trained commissioning
SOP
and SOP to
created and
signed off for
training.
Equipment
operation Utility Impact
Utility interferes with Assessment/
Operations cGMP Medium Medium Medium High Low SOP
Requirements other equipment Change
in the same Control/ SOP
room
Commissioning
Safety checks,
Equipment is
and SAT checks
Equipment Operation cGMP not safe to High Medium High High Medium SAT
to ensure safety.
operate
PUWER risk
assessment.
Equipment Training/ Training & Sign
Operations cGMP Setup incorrect Medium Medium Medium High Low
Setup SOP off against SOP.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
EPROM does Checks made
not have the during SAT and
SAT/
Power Failure latest version of any changes/ or
Equipment Business Critical Medium Low Low High Low Change
Recovery the software deviations noted
Control
after SAT in change
changes control.
Batch data lost SOP to train out
Power Failure Training/
Equipment Business Critical when equipment Medium Low Low High Low process for
Recovery SOP
power restored recovery.
Previous version
of the software Training and SOP to train out
Power Failure
Equipment Business Critical loaded after Medium Low Low High Low Maintenance process for
Recovery
power SOP recovery.
restoration
Checked during
Equipment Safety Steam Valve SAT/ SAT and added
cGMP High Low Medium High Low
Alarms Devices failure Maintenance to Maintenance
schedule
Checked during
Equipment Temperature SAT/ SAT and added
Sensors cGMP High Low Medium High Low
Alarms sensor failure Maintenance to Maintenance
schedule
Checked during
Unloading door
SAT/ SAT and
Equipment Interlocks cGMP opens after a Medium Low Low High Low
SOP regular SOP
Bowie Dick Test
checks
Checked during
Both doors open SAT/ SAT and
Equipment Interlocks cGMP Medium Low Low High Low
at the same time SOP regular SOP
checks

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Checked during
Unloading door
SAT/ SAT and
Equipment Interlocks cGMP opens after cycle High Low Medium High Low
SOP regular SOP
failure
checks
Algorithms used
in the Checked at
Functional
Control Algorithm calculation of Functional
cGMP High Low Medium High Low Specification/
System Verification critical Specification
SAT
parameters is review and SAT
incorrect
Operator panel
Operator Checked during
does not
Control Panel and SOP/ SAT and
Operation function as Medium Low Low High Low
System Screen Maintenance normal
specified in the
Navigation operation.
operator manual
Checked during
Security levels SAT and set-up
Control SOP/
Security cGMP not set up on the Medium Low Low High Low during Training
System Training
software and SOP
created.
The results on
Calibration/ Checked during
the printed
Control Report Maintenance/ SAT and set-up
cGMP report do not Medium Low Low High Low
System Generation Training/ during system
match the
SOP Calibration.
displayed values

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
The values used
for the display
and printed Calibration/ Checked during
Control Report reports are taken Maintenance/ SAT and set-up
cGMP Medium Low Low High Low
System Generation at different Training/ during system
times in the SOP Calibration.
cycle by the
software.
Checked during
Report And
Control The data is lost Training/ SAT and set-up
Data cGMP Medium Low Low High Low
System when archived. Maintenance during system
Archiving
maintenance.
Checked during
The data is
Report And System SAT and set-up
Control corrupted or
Data cGMP Medium Low Low High Low Maintenance/ during system
System changed when
Archiving Training maintenance
retrieved
training.
Checked during
Report And The report batch System SAT and set-up
Control
Data cGMP numbers are Medium Low Low High Low Maintenance/ during system
System
Archiving changed. Training maintenance
training.
Checked during
The software
Report And System SAT and set-up
Control does not allow
Data cGMP Medium Low Low High Low Maintenance/ during system
System the retrieved file
Archiving Training maintenance
to be viewed
training.
Checked during
Report And The software is System SAT and set-up
Control
Data cGMP not available for Medium Low Low High Low Maintenance/ during system
System
Archiving retrieval of data Training maintenance
training.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Checked during
The incorrect
SAT and set-up
Control Recipe parameters are Training/
cGMP High Low Medium High Low during Training
System Loading loaded in to the SOP/ O&M’s
and SOP
cycle
created
The software
Refer to
Control Recipe does not store Training/
cGMP Medium Low Low High Low supplier O&M’s
System Changes changes made to SOP/ O&M’s
and SOP
the recipe
The parameters
required to
move from one Refer to
Control Recipe Training/
cGMP phase to the next Medium Low Low High Low supplier O&M’s
System Changes SOP/ O&M’s
cannot be and SOP
changed on the
recipe screen.
Counter/ The counter Refer to
Control Training/
Sequence cGMP does not log all Medium Low Low High Low supplier O&M’s
System SOP/ O&M’s
Verification cycles and SOP
The counter
Counter/ Refer to
Control does not log Training/
Sequence cGMP High Low Medium High Low supplier O&M’s
System aborted or failed SOP/ O&M’s
Verification and SOP
cycles
The clock does
Counter/ Refer to
Control not record the Training/
Sequence cGMP High Low Medium High Low supplier O&M’s
System correct time SOP/ O&M’s
Verification and SOP
(GMT)
The phase
Checked and
parameters in
Equipment Operational SAT/ documented
cGMP the software Medium Low Low High Low
Operation Sequence PQ during SAT and
cause the cycle
PQ.
to abort

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
The temperature
in the chamber
does not meet Checked during
Equipment the specification SAT/ Autoclave
cGMP High Low Medium High Low
Operation in EN285 and PQ Commissioning,
Temperature HTM 2010 for SAT & PQ
Distribution Steam
Sterilization.
Checked during
There is uneven SAT/
Equipment Autoclave
cGMP heat distribution High Low Medium High Low PQ (Bowie
Operation Commissioning,
in the chamber Dick Tests)
SAT & PQ
Checked during
Air is not
Equipment Autoclave
cGMP removed from Medium Low Low High w SAT/ PQ
Operation Commissioning,
the equipment
SAT & PQ
Air Removal
Leak Rate Tests
There is an air
Equipment during
Operation leak in the Medium Low Low High Low SAT/ PQ
Operation commissioning,
chamber
SAT & PQ
Checked and
documented
Steam does not
Equipment Validation - against current
cGMP penetrate the High Medium High High Medium
Operation PQ validated load
equipment
Steam profiles during
Penetration PQ.
Equipment There are high Clean Steam
Operation levels of Quality Clean Steam to
cGMP High Medium High Medium High
Equipment particulates in Testing be quality tested
Operation the steam supply

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
To be checked
The equipment
and documented
orientation
Equipment Condensate PQ testing during PQ with
Operation causes drainage High High High High Medium
Operation Removal and SOP current
problems i.e.
validated load
Wet Loads
profiles.
To be checked
and documented
High levels of
Equipment PQ – BI during PQ with
Bio-burden cGMP bioburden on the High Medium High High Medium
Operation testing current
equipment.
validated load
profiles.
Sanitization To be checked
Load cycle High Low Medium High Low SAT/ PQ and documented
failure during PQ
Loading PQ Testing to
conditions use worst case
High Low Medium High Low PQ testing
change each load on all
time cycles.
Equipment
121°C Cycle cGMP PQ Testing to
Operation Sterilization
use worst case
Load cycle High Low Medium High Low SAT/ PQ
load on all
failure
cycles.
PQ Testing to
Sterilization
use worst case
Load does not High Low Medium High Low PQ testing
load on all
sterilize
cycles.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
PQ Testing to
Sterilization
include
conditions not
thermometric
achieved High Low Medium High Low PQ testing
testing and
throughout the
microbiological
load
indicators
Cycle phase
To be checked
time out due to
High Low Medium High Low PQ testing and documented
insufficient air
during PQ
removal
Sanitization To be checked
Load cycle High Low Medium High Low SAT/ PQ and documented
failure during PQ
PQ Testing to
Sterilization
use worst case
Load cycle High Low Medium High Low SAT/ PQ
load on all
failure
cycles.
PQ Testing to
Sterilization
use worst case
Load does not High Low Medium High Low PQ testing
Equipment load on all
134°C Cycle cGMP sterilize
Operation cycles.
Cycle phase
To be checked
time out due to
High Low Medium High Low PQ testing and documented
insufficient air
during PQ
removal
Cycle phase
time out due to PQ testing/ To be checked
insufficient Medium Medium Medium High Low Bowie Dick and documented
steam test during PQ
penetration

Downloaded from www.sterilize.it 18

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
To be tested and
documented at
SAT/ PQ. SOP
to refer to
Equipment Bowie Dick Maintenance/ trouble shooting
Quality Assurance Test cycle fails High Low Medium High Low
Operation Test O&M and Supplier to
provide
technical
support for new
Autoclave
To be tested and
documented at
SAT/ PQ. SOP
to refer to
Equipment Water Maintenance/ trouble shooting
Quality Assurance Test cycle fails Medium Low Medium High Low
Operation Intrusion Test O&M and Supplier to
provide
technical
support for new
Autoclave
Photos of the
loads (OQ).
Schematics to
Step 1 Incorrect be included in
Equipment
Equipment Product Quality sterilization High Medium High Low High SOP Training the SOP.
Loading
Preparation loads Worst-case
loads to be
verified in the
OQ and PQ.

Downloaded from www.sterilize.it 19

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Photos of the
loads (OQ).
Schematics to
Incorrect
be included in
Product Quality sanitization High Medium High Low High SOP Training
the SOP.
loads
Worst-case load
to be verified in
the OQ and PQ.
Equipment Chamber size Dimensional
Low Low Low Low Medium SAT
Critical incorrect checks (IQ).
Worst case
Maximum load loads to be
Product Quality High Medium High Low High SAT
weight exceeded verified in the
OQ.

Photos of the
loads (OQ).
Schematics to
Step 1 Equipment Loading pattern be included in
Product Quality High Medium High Low High None
Equipment Loading incorrect the SOP.
Preparation Temperature
Mapping Of
The Loads.

Downloaded from www.sterilize.it 20

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Photos of the
loads (OQ).
Equipment Schematics to
orientation be included in
incorrect the SOP.
High
causing B.Is to be put
Product Quality (Cycle Medium High Low High None
ineffective air into the load to
failure)
removal and verify that there
Equipment
condensate is sufficient air
Loading
drainage removal and
steam
penetration
Medium
(Not the
Wrong SOP and
Process Critical final Medium Medium Low High None
autoclave used training.
sterilizing
step)
SOP and
Medium
training. The
Step 2 (Not the
Cycle Wrong cycle sterilization and
Equipment Product Quality final Low Low Low Medium None
selection selected sanitization
Operation sterilizing
cycles will be
step)
the same.
The system
aborts the cycle
Step 2
Compressed air with critical
Equipment Utilities Equipment Critical Low Low Low Low Medium None
failure alarms. Alarms
Operation
will be verified
in the OQ

Downloaded from www.sterilize.it 21

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
The system
aborts the cycle
Failure of
with critical
Equipment Critical modified steam Low Low Low Low Medium None
alarms. Alarms
supply
will be verified
in the OQ
The system
aborts the cycle
Failure of new with critical
Equipment Critical High Low Low Low Medium None
Steam valve alarms. Alarms
will be verified
in the OQ
The system
Demineralized
aborts the cycle
Step 2 Water failure
with critical
Equipment Utilities Equipment Critical affecting the Low Low Low Low Medium None
alarms. Alarms
Operation jacket
will be verified
temperature
in the OQ
The system
aborts the cycle
with critical
alarms. They
will be verified
in the OQ. No
Equipment Critical Power failure Low Low Low Low Medium None
UPS. Machine
stops. Data
downloaded via
Ethernet
connection to
PC.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
The system
aborts the cycle
Step 2
with critical
Equipment Utilities Equipment Critical Vacuum Failure Low Low Low Low Medium None
alarms. Alarms
Operation
will be verified
in the OQ
All measuring
instruments will
be listed in the
IQ and their
criticality
Step 2
Measuring Instruments not assessed.
Equipment Process Critical High High High Low High None
Instruments calibrated In-process
Operation
Critical
instrument
calibration will
be verified in
the IQ.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
A Calibration
Specification
will be prepared
based upon the
User
Instruments
Requirements.
calibrated to the
Step 2 This is used to
Measuring incorrect
Equipment Process Critical High Low Medium Low High None check for the
Instruments specification
Operation correct
leading to errors
calibration
in the results
accuracy.
controls,
maintenance
and calibration
of instruments.
An
Collection of
independent
data will be
chart
Data not logged verified in the
Product Quality High Medium Medium Low High recorder
Step 2 by the software OQ. Data will
(cGMP) is
Equipment Software be checked for
attached to
Operation each batch.
the system.
Software errors
Verified in the
Product Quality causing alarms High Low Medium Low High None
OQ
or incorrect data

Downloaded from www.sterilize.it 24

Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Verified in the
SAT and OQ.
The control
system printout
cannot be used
as evidence of
Data not
sterilization, it
Step 2 transferred
is for
Equipment Hardware Product Quality correctly onto High Low Medium Low High None
information
Operation the printed
only. The two
report
reports will be
compared
during OQ.
A CFR Part 11
assessment to
be performed.
The software
will be
password
protected with
different access
Step 2 Parameters
Equipment/Process levels. Verified
Equipment Software changed on the High Low Medium Low High None
Critical in the OQ.
Operation cycle
These will then
be validated
cycles and
documented in
the SOP.
Step 2 A 21 CFR
Software not 21
Equipment Software Equipment Critical High Low Medium Low High None Assessment will
CFR compliant
Operation be performed.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Software is Revision history
Change
upgraded during to be covered
Control/
Equipment Critical commissioning High Low Medium Low High under Change
Validation/
so parameters Control during
HTM 2010
are changed. the validation.
The procedure
Yokogawa Chart
will be verified
Recorder not
in the OQ. This
Product Quality started at the High Low Medium Low High None
will be included
beginning of the
in the SOP and
cycle
training.
SOP and
training.
Medium There is an
High
(Not the operator check,
Incorrect cycle (Incorrect
Low final Low High None a second
selected temperature
sterilizing supervisor
selected)
step) check and the
Step 2 cycle traces are
Control
Equipment Product Quality also checked.
System
Operation The
Results changed
Engineering
on routine tests,
department
for example,
controls access
Bowie Dick, by High Low Medium Low High None
to the
manipulation of
instruments,
instrument
which are inside
readings
the unit.

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Project: Replacement of the Steam Sterilizing Autoclave - Risk Assessment
Assessment of Risk
Sub-
Function Probability Controls Risk
Functions Severity of Likelihood Overall
Details Relevance Risk Scenarios Class of In Place Management
Details Impact of Impact Priority
Detection
Critical alarm
not logged
Verified in the
because of High Low Medium Low High None
OQ.
active non-
critical alarm
Cycle not
aborted with
active critical
alarm because Verified in the
High Low Medium Low High None
active non- OQ.
critical alarm
not
acknowledged
This will be
included in the
Vent Filter Planned
damaged Preventative
Step 2
causing Maintenance
Equipment Filters Product Quality High Low Medium Low High None
contamination of System.
Operation
the air supply Integrity
Testing
Pre-filters in
place.
Pre-filters
Integrity
Step 2 damaged
Testing
Equipment Filters Product Quality causing High Low Medium Low High None
Pre-filters in
Operation contamination of
place.
the air supply
Dirty equipment
Step 3
Equipment removed from SOP and
Cycle Product Quality High Low Medium Low High None
Unloading unloading side training.
Completion
of autoclave

Downloaded from www.sterilize.it 27

 Key:

BI - Biological Indicator
IQ - Installation Qualification
O&M - Operation and Maintenance
OQ - Operational Qualification
PQ - Performance Qualification
PC - Personal Computer
SOP - Standard Operating Procedure
SAT - Site Acceptance Test
UPS - Uninterruptable Power Supply

Downloaded from www.sterilize.it 28

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