Biomedical Engineering Reference
In-Depth Information
have been isolated from the product, but also to choose highly resistant
organisms that could someday be encountered in the bioburden. The inactivation
kinetics of each of these microorganisms to the proposed process is determined,
and at least five time-points must be included, with at least a demonstration of
10
3
kill rate of the process for each organism. The inactivation curves are used to
establish the sterilization times, where the time is based on the most resistant
organism tested. Such a method ensures at least a 10
ÿ6
SAL of the process. ISO
14160 (1998) contains informative guidance in the annexes of the document to
assist in understanding what must be done, but it is highly recommended that an
experienced microbiologist be hired or used as a consultant during the
development and validation of the sterilization process.
While liquid chemical sterilization is the method of sterilization used today
for bioprosthetic heart valves, it has its disadvantages, particularly for the user of
the device. Residual chemical sterilant must be repeatedly rinsed from the
device before implantation, and this can lead to delays during the surgical
procedure. The remaining liquid sterilant in the container must be disposed of by
the hospital staff, and typically this must be collected and discarded as chemical
waste. Because of these inconveniences, which also represent safety hazards at
some basic level, there is continued interest in challenging the previous thought
that some of the more routine sterilization methods could not be used for
bioprosthetic valves.
Duran et al. (2001) have developed a means of treating tissues with a water-
soluble polar solvent to replace the water in the tissue with a mixture of low and
high molecular weight ethylene glycols. Thereafter, the tissue can be freeze-
dried for storage, while retaining its flexibility. Donnelly et al. (1973) reported
that freeze-drying produces large vacuoles in the porcine aortic valve tissue, and
questioned its utility in valve sterilization. Chen and Wika (2003) developed a
means of drying tissues with glycerol, which stabilizes the tissue dimensionally
such that the process can be applied to finished heart valves. The dried tissue can
then be sterilized using ethylene oxide or ionizing radiation. When the valve is
ready to be used, it can be implanted dry or rehydrated before use, and the tissue
will return to its original physical dimensions and mechanical properties. Shamis
and coworkers (2009) have evaluated the use of microwave radiation as a new
sterilization technique for bovine pericardial tissues. Their studies demonstrated
that the use of nonthermal microwave radiation did not alter the mechanical
properties of the pericardium, although they did not achieve complete
sterilization in their study.
Modern e-beam facilities enable biological materials to be irradiated frozen
or refrigerated, thereby reducing the damage that e-beam-generated free radicals
can cause to the biological material without interfering with its ability to kill the
microorganisms (Calhoun et al., 2008). The e-beam dose can be delivered in two
separate treatments, with a cooling period between the two treatments, to further
minimize damage to sensitive biological materials. Sometimes the delivery rate
