Page 222 - Assurance of Sterility for Sensitive Combination Products and Materials

Risk to the patient—Quantifying assurance of sterility 201

a large proportion of these skin scales will be contaminated with species of
the normal skin flora [5]. A key point, however, is skin flora are mainly non-
pathogenic micrococci, diphtheroids, and staphylococci. Other organisms
(e.g., Salmonella and Escherichia coli), not part of the resident skin flora, may also
be carried transiently on the skin surface and become a source of contamina-
tion [5]. This source of contamination is well recognized and manufacturers
utilize good hygienic practices to control this source of bioburden.
Given these factors and contamination from skin flora is mainly non-
pathogenic, the probability of viable pathogenic organisms is conservatively
−1
estimated at 0.5. P4 = 0.5 (5 × 10 ).
Thus, the estimated overall probability of infection for the conser-
vative case and more aggressive case of the examples above is shown in
Table 7.9 for a terminal sterilization process of a process that can achieve
−6
an SAL of 10 .
The analysis alone (see also below) concludes in the conservative case
scenario, there is a minor reduction in the overall probability of risk of in-
fection while the more aggressive case predicts a substantial decrease in the
risk of infection.
As noted in the introduction of Section 7.4.1, the application of this
−4
analysis could be applied for the special case of using an SAL of 10 for
−6
a product that cannot withstand sterilization to 10 . This is shown in
−6
Table 7.9B. The more aggressive case estimates an SAL of 10 . This puts
into perspective the low patient risk of this scenario.

Table 7.9 An estimated overall probability of infection.
Conservative case More aggressive case

Panel (A)
P1 1 × 10 –6 1 × 10 –6
−1
P2 1 0.1 (1 × 10 )
−1
P3 1 0.2 (2 × 10 )
−1
−1
P4 0.5 (5 × 10 ) 0.5 (5 × 10 )
Overall probability 5 × 10 −7 1 × 10 −8
Panel (B)
P1 1 × 10 –4 1 × 10 –4
−1
P2 1 0.1 (1 × 10 )
−1
P3 1 0.2 (2 × 10 )
−1
−1
P4 0.5 (5 × 10 ) 0.5 (5 × 10 )
Overall probability 5 × 10 −5 1 × 10 −6