Page 241 - Assurance of Sterility for Sensitive Combination Products and Materials

Developing new products 217

A third alternative approach to minimize the impact of sterilization on the
component is to alter the sterilization conditions. Reduction of temperature
or exposure time may be effective solutions for most sterilization modalities.
For example, if temperature during exposure is an issue, moving from gamma
radiation to e-beam can enable the product to be realized. The documented
justification why alternative established sterilization modalities are not viable
options is an integral part of the due diligence to justify alternate SALs.

8.4.2 Reducing exposure time
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The second approach to achieving a 10 SAL is to explore packaging
changes or sterile load configurations that will reduce the exposure time.
Understanding how the product and packaging interacts with the sterilizer
provides the sterilization professional critical process parameters or leavers
to impact component compatibility. For example, product is exposed to a
distribution of doses during radiation sterilization. Understanding the dos-
ing at a granular level enables the sterilization professional to modify the
load configuration to narrow the distribution of dose (maximum to mini-
mum). This allows a reduction in both the nominal as well as the maximum
dose. For ethylene oxide sterilization, the duration of the cycle is dependent
on the diffusion of the sterilant into the product. Changing the design of
the packaging to increase the area of Tyvek to increase the gas exchange or
decreasing the path length of narrow channels can reduce overall exposure
times of the product to the sterilant.

8.4.3 Reducing bioburden
The third option, reducing the bioburden load, enables an alternative ap-
proach to reducing exposure time. Bioburden-based sterilization validation
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methods achieve a 10 SAL based on the initial bioburden. Reduction
in the average bioburden enables lower exposure to achieve a given SAL.
The distribution of bioburden is typically non-normal with just a few units
having orders of magnitude higher levels of microbes than the rest of the
population of units. A single unit with a high bioburden load can have a
disproportionately large impact on the averages. Minimizing these “high
fliers” can significantly reduce the sterilizing dose.
A key to improved bioburden control is to understand their sources.
Microbial monitoring is invaluable to develop effective controls. Common
sources of contamination control include raw material controls, gowning
and handling procedures, and presterilization of subassemblies. An alternate
method to establish the sterilization process is another approach particularly