Biomedical Engineering Reference
In-Depth Information
requirement of the heart valve regulations to demonstrate a sterility assurance
level (SAL) of 10
ÿ6
(ISO 5840, 2005). This can also be stated as the need to
develop a process which can demonstrate a 6-log reduction in bioburden. If your
incoming tissue is highly contaminated, however, it can have a bioburden of
more than 10
6
viable microorganisms per tissue. If that is the case, a process that
provides a SAL of 10
ÿ6
will not provide a sterile product. That is, the incoming
tissue was so contaminated that its bioburden level overwhelmed the process's
ability to kill microorganisms, and thus some extraordinary actions must then be
taken. Because of the risk of a non-sterile product, the usual action that is taken
in such a case is to discard the tissue. As this has an associated cost in terms of
monetary loss, as well as loss in starting materials, this cannot be a regular
occurrence. If it is, then something about the process must be changed to prevent
this from occurring regularly. In a manufacturing environment with a well-
established quality system, there should be alert levels and action levels estab-
lished on bioburden, in order to ensure that the incoming bioburden never
exceeds the SAL of the process.
Ideally, you would never receive tissue with more than a million viable
microorganisms, but this can easily occur, especially when working with
abattoirs that are not sensitive to the high cleanliness standards of the medical/
pharmaceutical industry. Other factors can also contribute to higher incoming
bioburden, such as extended shipping times, or delays in receiving fresh tissues.
This is particularly a problem for US-based companies wishing to comply with
worldwide regulations on minimizing the risk of BSE. One universally accepted
way of meeting those regulations is to source tissues from a country with a
minimal risk of BSE, such as Australia or New Zealand. While it is possible to
express-freight a chilled cooler of tissue to the US in 24 hours, it can be difficult
to ensure the shipment will be released through US Customs, FDA, and USDA,
all in the same day that it was received. It is likely that a delay of at least 24±48
hours will occur during this release process, before the tissue can be shipped to
your facility. If it is a Friday by then, will you process the tissue immediately, or
place it in the refrigerator for the weekend? Delays in processing will also
increase the bioburden of the tissue.
From the moment the tissue is received, it should be your goal to try to reduce
bioburden. This can be accomplished via a number of different mechanisms.
First, prompt processing of the tissue once it is received. Second, vigorous
rinsing of tissue is useful in mechanically removing microorganisms from the
tissue. A typical rinsing regimen will involve a series of rinses, usually three
consecutive rinses, prior to selecting tissue for fixation. Fixation with
glutaraldehyde will reduce the bioburden significantly, and thus was its original
intent when Professor Carpentier fashioned the first glutaraldehyde-treated
porcine aortic valves. But how much does your fixation process reduce bio-
burden, and does it affect all the possible microorganisms that might be
contained on your tissue? As we have seen from previous examples, if you use a
