Page 47 - Assurance of Sterility for Sensitive Combination Products and Materials

Terminal sterilization 35

These processes are being pushed to their limits in order to tighten ranges
as more innovative devices are being developed. Combination products in-
crease the challenge further as different product functions often have differ-
ent tolerances to the sterilization modalities. For example, a sensitive drug
with an electronic medical device will have increased stability issues with
both EO and radiation sterilization.
Established terminal sterilization methods may not be compatible with
new products. Alternative gas sterilization technologies provide an additional
tool to terminally sterilize innovative products. These technologies will be
referred to as alternative gas methods as opposed to the established EO gas
methods. The vendors of these alternative gas methods have taken a similar
approach as established methods to characterize effects on materials. AAMI
35
TIR 17:2008 expanded the scope of material evaluations to include radia-
tion, EO, moist heat (steam), dry heat, hydrogen peroxide, and ozone.
The alternative gas methods follow a similar sterilization validation
methodology as EO, with the general requirements detailed in ISO 14937:
2009 [29]. The physical sterilization processes are different from EO be-
cause of the nature of the three novel gases, for example, nitrogen dioxide,
vaporized hydrogen peroxide, and vaporized peracetic acid. All these gasses
have the ability to operate at ambient conditions with temperature ranging
between 18 and 30 °C. Although humidity typically ranges between 30%
and 100% for standard cycles, vaporized peracetic acid has the ability to
sterilize as low as 16%. As with any process, there are tradeoffs. As the dwell
time decreases, the relative humidity must increase to provide the microbial
kill. The standard full-length cycle of the alternative gasses is much shorter,
typically under 4 h. The cycle time for most of these alternative gasses is
much shorter than EO because the gasses and their breakdown products are
much less toxic than the carcinogenic EO.
The mechanism of gas delivery has changed dramatically. Rather than
an extended injection and dwell commonly used for EO, alternative gasses
are exposed to the product in multiple short pulses of specific duration and
dwell time. The gases are evacuated and exchanged with air between pulses
resulting in dramatically shorter product contact time. The unique prop-
erties of the gases, in combination with the dramatically lower exposure
times, result in an expanded list of compatible materials to screen during the
development of the product.
Exploitation of the unique properties of novel gasses may enable the
sterilization of new products. An example of this is the terminal sterilization
of pre-filled syringes. Sterilization gas with low permeability could enable