Biomedical Engineering Reference
In-Depth Information
the given operating environment. Proving that the conditions chosen will
effectively mitigate bioburden is part of the validation process.
As you can now appreciate, bioburden measurement and determination are
essential aspects of any facility manufacturing a tissue-based product (ISO
11737-1, 2006). Not only is it important to do this during the initial development
and validation of the process, but it is also important to do this routinely, to
make sure the bioburden has not changed significantly, either in amount (in
which case, the SAL of 10
ÿ6
may not be sufficient) or in the type of micro-
organism. Every manufacturing change that is considered must also be evaluated
from the perspective of its effect on the bioburden, whether it is a change in
supplier, cleaning procedures, or expanding production capacity by adding
another work shift. These and other changes have the potential to greatly
increase bioburden, and if you are not measuring it, you will not know it ± that
is, until the Center for Disease Control and the FDA appear at your door, and by
then it will be too late! It is best to keep your destiny in your control, and
regularly measure the parameters that have the most risk for creating a harmful
product. Bioburden is one of those critical parameters.
5.7.6
Sterilization
Sterilization of a bioprosthetic valve is complicated and unlike most other
devices. Because of the mixture of different synthetic and biologic materials
used, the traditional methods of sterilization including autoclaving, gamma
irradiation, e-beam treatment, ethylene oxide exposure, or peroxide plasma
sterilization typically are not used. Because of the increasingly widespread use
of bioprostheses and other tissue-based products, guidelines have been published
on the use of liquid chemical sterilants to ensure terminal sterilization of the
device (ISO 14160, 1998). These guidelines include a discussion of the quality
system requirements for the manufacturer, a description of process development
and product compatibility with the proposed terminal liquid sterilization (TLS)
method, and a detailed discussion of the validation of the method.
There are a number of considerations that go into designing a suitable TLS
method. First, the sponsor must know the bioburden (amount and type) of the
product prior to application of the TLS method. Second, they must know that the
product can still perform adequately after the sterilization process, and typically
this is tested after worst-case conditions, such as excessively long exposure
times which may simulate an equipment failure, or the need to repeat a
sterilization cycle. The test methods themselves must be validated prior to use in
the sterilization validation, to ensure that the methods do not generate erroneous
results. For example, residual liquid chemical sterilant must be neutralized prior
to culturing for surviving microorganisms.
The choice of microorganisms used in the performance qualification of the
device is essential. It is important to test both representative microorganisms that