Page 221 - Assurance of Sterility for Sensitive Combination Products and Materials

200 Assurance of sterility for sensitive combination products and materials

for P2 would be a 1 in 10 chance that an organism would be viable at the
time of use on a patient, possibly based on the bioburden having vegetative
bacteria only, the product being one that does not support growth, the lead
time from sterilization to use being longer, and there being uncontrolled/
hostile shipping/storage conditions.
If a product is capable of supporting growth, then maybe a 1 in 1 like-
lihood of a surviving organism still being viable at the time of use, and at
minimum P2 = 1.
For this example P2 (conservative case) = 1 while P2 (more aggressive
−1
case) = 0.1 (1 × 10 ).
7.4.1.3 Probability of P3
The third factor is the probability of introducing viable organisms into
the patient. This factor assumes the surviving organism (a) is transferred
from the package to the device if it is on the interior of the package,
(b) is resident on the device, (c) is not removed during device prepara-
tion, (d) resides on a part of the device that contacts the patient, or (e)
resides on a part of the device that contacts the user and is transferred
to the patient and the organism is not removed during handling. Using
facts such as the portion of the device that contacts the patient being 20%
of the device, one could use a conservative likelihood of 1 in 5. In this
−1
example P3 = 0.2 (2 × 10 .) A very conservative approach would assume
the organism is introduced despite the location, possibility of removal or
possibility of transfer.
For this example P3 (conservative case) = 1 while P3 (more aggressive
−1
case) = 0.2 (2 × 10 ).

7.4.1.4 Probability of P4
The fourth factor, the probability of an organism being pathogenic is con-
tingent on the types of organisms prevalent in the manufacturing envi-
ronment and on the bioburden of the product materials. Organisms from
the manufacturing environment are of less concern since there is no direct
product contact, however, controls are still required. Environmental con-
tamination of dry surfaces such as floors and walls comprise mainly Gram-
positive rods, cocci, and fungal spores. Gram-negative bacteria are more
susceptible to the lethal effects of drying, but small numbers may persist on
dry surfaces for substantial periods [6].
Contamination from process operators is considered a significant source of
4
−1
risk. During normal activity, loss of skin scales by shedding is about 10 min ;