Page 46 - Assurance of Sterility for Sensitive Combination Products and Materials

34 Assurance of sterility for sensitive combination products and materials

process. Materials react differently to the modality chosen. Sensitive combi-
nation devices should not only focus on material compatibility, but also on
how things such as the active ingredients react during sterilization and the
shelf life of the product after sterilization.
There are multiple approaches to the validation of a terminal steriliza-
tion process: bioburden-based approach, bioburden and BI-based approach,
and biological indicator approach (overkill). All three methodologies are
based on understanding the impact of the sterilant on the microbial biobur-
den or surrogate. All three methods tend to overestimate the SAL because
of inherent safety factors that are added to the method. The relative safety
factor tends to increase, going from the bioburden-based approach to the
bioburden and BI-based approach to the BI approach. These approaches
developed for radiation, EO, and dry/moist heat sterilization can be applied
to other sterilization modalities.

3.3 Future approaches to sterilization
There is a growing number of products that are submitted to the Food and
Drug Administration (FDA) that utilize sterilization processes beyond the
traditional methods, which are referred to as established methods given the
history and longtime acceptability. The FDA guidance considers these new
sterilization technologies to be novel methods [28]. Established sterilization
methods have a history of being applied to many products and understand-
ing of effects on materials. They are divided into two categories: A and B.
Category A includes methods with a long history such as radiation, EO, and
dry/moist heat. Category B includes methods that are newer but still have
precedence with the methods being applied to products, such as hydrogen
peroxide, ozone, and flexible bag EO systems. Novel methods such as va-
porized peracetic acid, microwave radiation, sound waves, and ultraviolet
light, have very limited data.
Established methods have worked successfully with typical materials
found in single-use medical device products and will likely continue to do
so in the future. With continuing innovations in electronics, materials, diag-
nostics, controlled and targeted delivery as well as active ingredients (par-
ticularly biologics) the limitations of the established methods are becoming
apparent. The complexities of sensitive combination products have intro-
duced new material compatibility challenges. The current simple devices
are tolerant to the sterilant and processing conditions optimized for these
devices, but this might no longer be adequate for more sensitive devices.