Biomedical Engineering Reference
In-Depth Information
0.2% solution of glutaraldehyde, you will not have a process that is entirely
effective in killing viable Mycobacterium cholonei. Therefore it is essential in
any good manufacturing process to measure your incoming bioburden,
understand how changes in vendors and shipping and other parameters can
affect it, and to also characterize the main species within your bioburden. Do
you have aerobic bacteria? Anaerobic bacteria? Molds and fungi? While this
chapter is not intended to provide an extensive training on microbiology, it
should educate you on the important issues that you will face in a heart valve
development project. In the case of microbiology, make sure you work with
someone who is well trained and has experience in heart valve manufacturing
and quality assurance.
After the tissue has been crosslinked, the initial bioburden will be reduced,
but it will not necessarily be completely eliminated. Therefore it is necessary to
introduce a bioburden reducing step, which is usually composed of a more
aggressive chemical cocktail, such as a mixture of formaldehyde±ethanol±
Tween (Nashef and Ahmed, 1989) or a high concentration of glutaraldehyde
with alcohol (Lentz and Pollock, 1982). The exact composition and exposure
conditions would depend upon your residual incoming bioburden after fixation,
but they could include prolonged exposure times, elevated temperatures, or both,
if necessary. A process of systematic determination of bioburden reduction rates
as a function of solution composition and concentration, as well as optimization
of process time and temperature, combined with the knowledge of your residual
bioburden after fixation, will help you determine the precise processing condi-
tions required. The goal at this point should be complete elimination of the
incoming bioburden without placing unnecessary restrictions on the manufac-
turing department.
Once you have sterilized the tissue from its incoming bioburden, you must
continue to monitor bioburden, as the process of manufacturing a valve will also
contribute bioburden to the tissue. The amount of bioburden added by the
process during valve fabrication is very much a matter of the cleanliness of your
facility, the operating environment and its control, the number of personnel in
the room and their work practices, and the cleanliness of everything going in to
the process/product/environment. All these factors must be considered and
controlled to minimize the contamination of the valve by the process. After the
valve is fabricated and tested, it is typical to subject the valve once again to a
bioburden reduction step, to protect the valve from the bioburden generated by
the process. Ensuring the bioburden reducing step is effective will be done by
measuring, on a regular basis, the bioburden of the product as it is built, and
characterizing its species. Because this bioburden was caused by the manu-
facturing process, it is likely to be different from the incoming bioburden from
the abattoir. It is possible that the two bioburden reducing steps will require two
different chemical solutions, or at least different conditions of time and/or
temperature. Again, these parameters will have to be developed specifically for
