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Risk to the patient—Quantifying assurance of sterility 203
• annual certification of classified spaces to ensure engineering con-
trols are acceptable,
• routine maintenance of the heating, ventilation, and air conditioning
(HVAC) system,
• facility housekeeping procedures typically include cleaning and
refuse removal, frequency of cleaning, approved cleaning agents/
chemicals, and documentation of these activities,
• pest control to prevent facility contamination by pests, and
• gowning procedures, which typically describe personal hygiene and
gowning requirements, instructions for cleaning individual stations,
associated equipment, and items being transferred into the controlled
environment.
7.4.2.3 Sterilization validation methodology
Some sterilization validation methodologies provide extra assurance the
PNSU* requirement is met, as seen in the statistical analysis of the quan-
tifiable aspects of a terminal sterilization overkill method (Section 7.3.5).
There are other considerations that can be significant contributing factors
to the assessment of patient risk, for example, when sterilizing a product
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at a PNSU* of 10 because it cannot withstand a PNSU* of 10 . These
considerations add to confidence that such a terminal sterilization process
will not result in significant risk to the patient.
An example of such a consideration is the conservative nature of the
delivered dose compared to the sterilization dose in radiation sterilization.
Terminal radiation sterilization processes result in a distribution of doses, not a
homogeneous sterilization dose. Therefore product receives a range of doses
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as well as a range of SAL values. For instance, when applying a 20 kGy 10
sterilization dose, a dose range of 20–35 kGy is common and would likely
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provide a PNSU* range of 10 –10 or less. This is illustrated in Fig. 7.14,
the distribution of doses received in a radiation sterilization dose map-
ping validation. The maximum PNSU* at the lowest dose received by the
product (in this case just above 20 kGy taking uncertainty into account), is
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<10 . The SAL at the center of the dose distribution to the product, in this
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case approximately 28 kGy, is approximately 10 .
As noted in the introduction of Section 7.4.1, the application of this
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analysis could be applied for the special case of using an SAL of 10 for a
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product that cannot withstand sterilization to 10 as per Fig. 7.14B. This
puts into perspective the low patient risk of this scenario; the SAL at the
center of the dose distribution to the product, in this case approximately
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21 kGy, is <10 .