Biomedical Engineering Reference
In-Depth Information
5.7 Additional considerations
5.7.1 Overall process design
In the initial processes which were employed, many companies took a
minimalist view towards glutaraldehyde, believing it to be the source of
irritation and toxicity, and resulting in calcification. With that view, they strove
to reduce glutaraldehyde concentrations as low as possible and to eliminate
glutaraldehyde wherever possible. In at least one case, the use of very low levels
of glutaraldehyde was associated with the persistence of viable Mycobacterium
chelonei in commercial product (Levy et al., 1977; Rumisek et al., 1985).
As a result of this experience, every commercial producer has implemented a
bioburden-reducing process into their valve manufacturing protocol. The key
process steps to a commercial process are thus: receipt of tissue from abattoir/
supplier; isolating desirable tissue and crosslinking it; exposing the tissue to a
bioburden-reducing treatment; implementing an optional calcification mitigation
treatment; cutting out the leaflets and fabricating the valve; and finally,
sterilizing the finished product. While it is beyond the scope of this chapter to
discuss each of these steps in detail, there are several items worth noting.
5.7.2
Tissue sourcing
An important consideration is the source of the tissue, not just the animal
species, but also the location and practices of the supplier of the tissues. In most
cases, this is the abattoir or a tissue broker. As was demonstrated in the 1980s, it
is possible for humans to develop disease by eating beef from cattle infected
with bovine spongiform encephalopathy (BSE) (Erdtmann and Sivitz, 2004).
Given the seriousness of the resulting disease, new variant Creutzfeld±Jacob
disease (nvCJD), and the inability of most known bioburden-reducing practices
to inactivate the organism responsible for disease transmission, the World
Health Organization (WHO) has worked with regulatory agencies worldwide to
adopt a policy of safe sourcing (EMEA, 2004).
Safe sourcing is a series of best-practices designed to safeguard the public by
minimizing the risk of transmitting BSE to humans through medicinal products
and devices. It includes demonstration of source controls to ensure that feed
does not contain proteins from ruminant sources. It continues with a demon-
stration of good veterinary practices, both at the farm and at the abattoir.
Abattoirs are required to employ trained veterinarians to inspect animals prior to
slaughter, as well as inspect the carcass during the slaughter process, in order to
evaluate the lymph nodes and other tissues which might signal a latent or
undetected disease in the animal. Abattoirs must have a means to isolate
questionable carcasses until further evaluation can be performed, and in general
to keep the tissues most likely to transmit BSE (specified risk materials, SRMs)
away from other tissues and organs that will be used in food, medicines, and
