Page 44 - Assurance of Sterility for Sensitive Combination Products and Materials

32 Assurance of sterility for sensitive combination products and materials

The bioburden and BI-based approach establishes a resistance pro-
file of the product bioburden against a BI. The BI is composed of a
homogenous population of an organism with a known resistance to the
sterilization process being validated. Bacillus atrophaeus is commonly used
for EO sterilization, while Geobacillus stearothermophilus is used for moist
heat. The BI is typically selected with a population equal to or slightly
greater than the product bioburden. Product samples and BIs are exposed
to graduated conditions and sterility tested to establish the resistance
profiles between the two populations. Once the comparative resistance is
known, the validation of the sterilization process can be executed with
only the BI.
The bioburden and BI-based approach introduces the concept of a
process challenge device (PCD), defined as an “item designed to constitute
a defined resistance to a sterilization process and used to assess performance
of the process.” [5] As previously discussed, the resistance of the product to
the sterilization process involves the product configuration, packaging, and
the types and quantities of organisms present. While validating the steril-
ization process with only the product bioburden, product configuration
challenges are inherent in the process—meaning the microbial flora and
the location on/in the device have already been considered in the vali-
dation approach (bioburden-based approach). When using a surrogate BI,
the difficulty of getting the sterilant to all locations in the device should
be challenged. This leads to the development of the PCD. An evaluation
of the product configuration and the packaging should determine where
the PCD/BI should be placed to create the greatest challenge to the ster-
ilization process. The comparative resistance of the BI and the bioburden
should account for the use of the PCD—the BI is placed in the most chal-
lenging location to sterilize.
The PCD may be generated by inoculating the actual product in dif-
ficult to reach locations, or may be composed of a surrogate device that
presents an equal or greater challenge to sterilize as the product and associ-
ated bioburden. Again, this is accomplished through product tests of sterility
following exposure to reduced, or fractional, conditions.
Once the PCD and the comparative resistance between the PCD and
bioburden are understood, the validation of the sterilization process is exe-
cuted using only the PCD. The PCD is exposed to incremental conditions
to establish the D-value. Once the D-value is understood, the exposure
conditions can be extrapolated to determine the final cycle conditions re-
quired to deliver the specified SAL.