Page 218 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 197

In light of new regulatory paradigms in ISO TS19930:2017 as described
in Chapter 9, this example could have used a hypothetical terminally ster-
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ilized product with a process to achieve a PNSU* of 10 , the P1 estimate,
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resulting in a real-world estimate of a PNSU* of 10 or 10 as shown
below. The analysis could also have used a hypothetical aseptic process with
a P1 estimate from Table 7.7. Estimates of P2, P3, and P4 will be similar for
all of these scenarios.

7.4.1.1 Probability of P1
The basic probability of an organism present on a sterile product is ini-
tially estimated via the PNSU* for terminal sterilization processes and
by the estimate of contamination rate in aseptic processing (quantified in
Section 7.3.3 as the UCB of the aseptic process).
Terminal sterilization processes result in SAL ranges. For example, a ra-
diation sterilization dose range of 20–35 kGy that would provide a PNSU*
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range of 10 to 10 or less, as discussed below and seen in Fig. 7.14.
However, for a risk analysis, the lowest assurance of sterility must be as-
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sumed, which would be 10 for this particular PNSU* range. For purposes
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of this analysis, a standard assurance of sterility, PNSU* of 10 , is assumed.
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Hence P1 = 1 × 10 .
7.4.1.2 Probability of P2
The next factor in this analysis is the probability of viable organisms at time
of use. This factor is contingent on several factors including the storage envi-
ronment, the time of storage, types of organisms and their ability to survive.
In the manufacture of health-care products, the environmental organ-
isms are usually expected to be similar, regardless of the nature of the prod-
uct [5]. The environmental isolates recovered during the manufacture of
biologics and tissue-based products are typically the same types as those
recovered in medical device manufacturing. Because the manufacture of
biologics and tissue-based products relies heavily on screening of materials
and high-level disinfection, the resulting bioburden of both categories of
health-care products is, in most cases, made up of commonly encountered
microorganisms from activities related to the environment and handling.
Any significant difference between the bioburden of these two categories
of health-care products will usually be due to the bioburden found on the
raw materials.
This common spectrum of bioburden flora is the basis of the effec-
tiveness of most terminal sterilization processes. Therefore, although the