Page 232 - Assurance of Sterility for Sensitive Combination Products and Materials

Developing new products 211

of success and allows timeline risk to be accurately estimated. Technical risk
is prioritized as the complexity and novelty of the product increases un-
certainty. An early literature review to evaluate material compatibility with
the various sterilization modalities will avoid the more costly build and test
strategy. This may provide an efficient and quick assessment as to whether a
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10 SAL is achievable.
The Association for the Advancement of Medical Instrumentation
(AAMI) has published an excellent resource “Compatibility of materials
subject to sterilization” TIR17:2017 [2], which enables the developer to
prioritize sterilization modalities based on general material compatibility
guidance. Initial testing of clinically relevant performance outputs will help
confirm risks and identify if additional resourcing would be required to
develop the product. Evidence that the product cannot be sterilized to a
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level of 10 SAL must be provided before other strategies such as aseptic
processing or an alternative SAL can be used.
Even after proof of principle has been confirmed, the development of
a robust and efficient sterilization process is important for the successful
development of the product. Ideally, if a pre- and poststerile correlation of
functional performance can be established, then the sterilization process can
proceed in parallel to the nonsterile device development. Often, however,
the relationship cannot be established because of the high variability in the
output. If the impact of sterilization on the output cannot be quantified,
then all the developmental studies that relate to those outputs will require
sterilization. Since the preliminary sterilization process is typically not op-
timized for efficiency, increased delays directly impact the critical path of
the program.
As the data package is being collected, other criteria such as the stability
of the product under accelerated aging at the sterilization process challenge
limits should be gathered to understand the robustness of the product to
the sterilization conditions. Accelerated aging is important because it is a
long lead time item. Challenge limits such as maximum acceptable dose for
radiation sterilization and challenge sterilization cycles for ethylene oxide
sterilization further aids in the assessment of the sterilization risk.
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In all three cases, terminal sterilization to 10 SAL is the default, unless
it can be demonstrated that it is unachievable. Only after it can be demon-
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strated that terminal sterilization at 10 SAL cannot be achieved can an al-
ternative SAL or aseptic processing can be utilized. The aseptic process and
the alternative terminal sterilization SAL process have taken slightly differ-
ent approaches to the demonstration that a product cannot be sterilized.