Contains Nonbinding Recommendations
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A. Evaluation of Local and Systemic Risks
Biological evaluation of medical devices is performed to determine the acceptability of
any potential adverse biological response resulting from contact of the component
materials of the device with the body. The device materials should not, either directly
(e.g., via surface-bound chemicals or physical properties) or through the release of their
material constituents: (i) produce adverse local or systemic effects; (ii) be carcinogenic;
or (iii) produce adverse reproductive and/or developmental effects, unless it can be
determined that the benefits of the use of that material outweigh the risks associated with
an adverse biological response. Therefore, evaluation of any new device intended for
human use requires information from a systematic analysis to ensure that the benefits
provided by the device in its final finished form will outweigh any potential risks
produced by device materials over the intended duration and use of the device in or on
the exposed tissues.
When selecting the appropriate endpoints for biological evaluation of a medical device,
one should consider the chemical characteristics of the device materials and the nature,
degree, frequency, and duration of exposure to the body (i.e., intended use), as outlined in
Attachment A. In general, the biocompatibility endpoints to be considered include: in
vitro cytotoxicity; acute, subchronic and chronic toxicity; irritation; sensitization;
hemocompatibility; implantation; genotoxicity; carcinogenicity; and effects on
reproduction, including developmental effects. However, depending on device physical
properties (e.g., surface topography, device geometry),
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the intended use of the device,
target population, and/or the nature of contact with the body, not every biocompatibility
endpoint will require testing. In contrast, the biocompatibility endpoints identified in
Attachment A may not be sufficient to demonstrate the safety of certain devices (e.g.,
devices that include submicron or nanotechnology components, see Section V.D). In
addition, biocompatibility endpoints such as neurotoxicity and immunotoxicity should be
considered for devices where local or end organ toxicity assessments relevant to the
implant location or toxicity issues of concern would not be assessed in a traditional
biocompatibility study. For example, a neurological device having direct contact with
brain parenchyma and cerebrospinal fluid (CSF) may necessitate an animal implant test
to evaluate its pathological and physiological effects (e.g., effects on the brain
parenchyma, neurobehavioral effects and/or neurological deficits, and effects on the
functional mechanisms of the choroid plexus and arachnoid villi to secrete and absorb
CSF). The specific clinical application and the materials used in the manufacture of the
new device will guide selection of the appropriate biocompatibility evaluations. Where
available, device-specific guidance documents may include additional safety assessments
to be considered within the context of a biocompatibility evaluation.
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For example, a material may be selected to provide a certain stiffness required for the device to perform
appropriately (i.e., device characteristic), but may also have other material characteristics that could impact the
biological response to the device (e.g., hydrophilic or hydrophobic surface).