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ABSTRACT
This paper addresses some of the risk considerations that must be evaluated when
replacing a steam sterilizing autoclave within a pharmaceutical processing facility. It
demonstrates the application of Failure Modes and Effects Analysis (FMEA) for
assessment of risk as part of quality risk management. Formal risk approaches
normally share four basic concepts including risk assessment, risk control, risk
review, and risk communication. 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. Before risks
can be managed, they need to be assessed. FMEA is a widely used risk assessment
tools. Steps to perform FMEA are identified; questions to be asked are listed.
Criteria for risk assessment must be defined. Either a numerical scoring system or
marker phrases such as high, medium, low may be utilized. Three areas are
evaluated: Severity of the hazard, likelihood of occurrence, and likelihood of
detection. Tables for classifying these aspects are provided. A team approach to risk
assessment is recommended. The risk assessment process is demonstrated using the
example of a steam sterilizing autoclave replacement.
INTRODUCTION
This paper addresses some of the risk considerations that must be evaluated when
replacing a steam sterilization autoclave within a pharmaceutical processing facility.
A cast study format is utilized. In outlining the key risk considerations, the paper
demonstrates 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 (1). Autoclaves are used within
pharmaceutical facilities to eliminate microbial cells and spores from within a given
device. Autoclaves commonly use steam heated to 115134C (250 273F). To
achieve sterility, a holding time of at least 30 minutes at 115C, 15 minutes at 121C
(250F) or 3 minutes at 134C (273F) is required (2).
The validation and verification of the sterilization process is well monitored in the
pharmaceutical industry. Operators must ensure that autoclaves comply with
various regulatory guidances 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
auspices of quality risk management.
Formal risk approaches normally share four basic concepts, which are listed below:
Risk assessment
Risk control
Risk review
Risk communication.
This paper considers the application of FMEA, failure modes and effects analysis, to
the replacement of a steam-sterilizing autoclave in a pharmaceutical manufacturing
facility.
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 for risk assessment is
Failure Modes and Effects Analysis (FMEA) (6).
FMEA is a highly structured approach and can be undertaken through the following
steps:
c) Setting scales for factors of severity, occurrence and detection (see below)
d) Process mapping
RISK CRITERIA
It is important to establish the risk assessment criteria as part of the risk assessment
exercise. 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.
FMEA may utilitze either a numerical scoring system or marker phrases such as
high, medium, low for quantitation. Marker terms are used in the following
case study.
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:
When these three are cross-compared, the overall risk can be established. The best
means to do this is through the use of risk 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
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
Risk Priority
Record the risk priority based upon the risk classification and probability of
detection from the table.
TABLE 2: RISK PRIORITY
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 that are 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:
The risk assessment process is outlined in Appendix I using the example of a steam
sterilizing autoclave replacement.
Equipment preparation
The defined loading of the autoclave with equipment to be sterilized in an important
sub-functional detail is in autoclave operation. The relevance of loading an autoclave
incorrectly significantly impacts 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.
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:
RISK EXAMPLE
Appendix I contains an example of risk assessment for a replacement steam-
sterilizing 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 may 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.
CONCLUSION
The final assessment of the FMEA risk exercise was that the new autoclave can be
fitted and that the risks are adequately controlled. It was noted that although the
new autoclave has 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 FMEA risk assessment methodology 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
FMEA KEY
BI - Biological Indicator
IQ - Installation Qualification
OQ - Operational Qualification
PQ - Performance Qualification
PC - Personal Computer