Biomedical Engineering Reference
In-Depth Information
produced by device materials. When selecting the appropriate tests for the
biological evaluation of a medical device, one must consider the chemical
characteristics of device materials and the nature, degree, frequency, and
duration of their exposure to the body. In general, the tests include acute, sub-
chronic, and chronic toxicity; irritation to skin, eyes, and mucosal surfaces;
sensitization; hemocompatibility; genotoxicity; carcinogenicity; and effects
on reproduction including developmental effects. However, depending on
varying characteristics and intended uses of devices as well as the nature of
contact, these general tests may not be sufficient to demonstrate the safety
of some specialized devices. Additional tests for specific target organ toxic-
ity, such as neurotoxicity and immunotoxicity, may be necessary for some
devices. For example, a neurological device with direct contact with brain
parenchyma and cerebrospinal fluid (CSF) may require an animal implant
test to evaluate its effects on the brain parenchyma, susceptibility to seizure,
and effects on the functional mechanism of choroid plexus and arachnoid
villi to secrete and absorb CSF. The specific clinical application and the mate-
rials used in the manufacture of the new device determine which tests are
appropriate. Some devices are made of materials that have been well char-
acterized chemically and physically in published literature and have a long
history of safe use. For the purposes of demonstrating the substantial equiv-
alence of such devices to other marketed products, it may not be necessary
to conduct all the tests suggested in the FDA matrix of this guidance. FDA
reviewers are advised to use their scientific judgment in determining which
tests are required for the demonstration of substantial equivalence under
section 510(k). In such situations, the manufacturer must document the use
of a particular material in a legally marketed predicate device or a legally
marketed device with comparable patient exposure.
International Guidance and Standards
In 1986, the FDA, Health and Welfare Canada, and Health and Social Services
UK issued the Tripartite Biocompatibility Guidance for Medical Devices. This
Guidance has been used by FDA reviewers, as well as by manufacturers of
medical devices, in selecting appropriate tests to evaluate the adverse biologi-
cal responses to medical devices. Since that time, the International Standards
Organization (ISO), in an effort to harmonize biocompatibility testing, devel-
oped a standard for biological evaluation of medical devices (ISO 10993). The
scope of this 12-part standard is to evaluate the effects of medical device
materials on the body. The first part of this standard, “Biological Evaluation
of Medical Devices: Part 1: Evaluation and Testing,” provides guidance for
selecting tests to evaluate the biological response to medical devices. Most
of the other parts of the ISO standard deal with appropriate methods to con-
duct the biological tests suggested in Part 1 of the standard. ISO 10993, Part 1,
and the FDA-modified matrix thereof, use an approach to test selection that
is very similar to the currently used Tripartite Guidance, including the same
