More
Than Materials: A Risk-Based Framework For
Biocompatibility Assessment
(Courtesy : Lubrizol Life Science Driven by Innovation,
Powered by Partnership)
The safety of a medical device is of
utmost concern and importance at all times during its
development, manufacturing, regulatory submission and
use. One critical step in establishing the safety of a
device is to evaluate how the device interacts with
the body. This is better known as the device
biocompatibility. Evaluation of biocompatibility
can be a complex topic involving many considerations,
starting from the materials of construction through
device design, processing, sterilization and
intended use. The evaluation can be at the material
level and the device level.
At the material level, USP Class VI is a group
of tests developed to evaluate materials intended for
use in medical applications. These rigorous tests
evaluate materials and their extractable substances
for the potential to cause toxicity and irritation.
The process provides basic assurances that the
materials are not inherently toxic when used in
medical applications. The tests include three in vivo
biological reactivity evaluations, generally performed
on mice or rabbits to
mimic use in humans.
ISO 10993 is a standard that covers evaluation of
medical devices that come into direct or indirect
contact with the human body for biocompatibility using
a risk-based approach. The biological evaluation of
the devices (and their materials of construction)
based on the overall device risk depends on a large
number of considerations, which are explored in part 1
of ISO 10993 (ISO 10993-1) and in the FDA’s recently
finalized updated guidance document on this standard.
Device makers’ materials suppliers may
be helpful in conducting the evaluations at both the
material and device levels.
A risk-based approach
ISO 10993 guidance emphasizes using a risk-based
approach. What exactly is a “risk-based approach?”
ISO 14971 defines the term “risk” as “the combination
of the probability of occurrence of harm and the
severity of that harm.” The standard defines harm
primarily as physical injuries and damage to health,
but it also includes harm to goods and to the
environment.
The risk-based approach adds the harm resulting from
regulatory non-compliance and bureaucracy. It is about
weighing the likelihood and the consequence of the
identified risks and adapting the expenditure of
resources accordingly.
As stated in ISO 10993-1 (page 9), “The biological
evaluation of a medical device (or a material
component of such) should be conducted within the
framework of a risk management process. Such a process
should generally begin with assessment of the device,
including the material components, the manufacturing
processes, the clinical use of the device including
the intended anatomical location, and the frequency
and duration of exposure. Considering this
information, the potential risks from a
biocompatibility perspective should be identified.
Once the risks have been identified, the [OEM] should
assess what information is already available regarding
those risks and identify the knowledge gaps that
remain. Considering the potential biological impact, a
plan should be developed to address the knowledge gaps
either by biocompatibility testing or other
evaluations that appropriately address the risks.” The
new, risk-based guidance moves away from a check-the
box approach to biocompatibility testing. One of the
FDA’s goals is to reduce unnecessary testing,
particularly animal testing, by giving preference to
chemical constituent testing and in vitro models where
these methods yield equally relevant information.
As intended by the FDA, more OEMs seem to be adopting
chemical characterization assessments as part of their
biocompatibility evaluation process. If an OEM has a
good, comprehensive chemical and physical
characterization of a material, it may not be
necessary to conduct testing for all or a portion of
the biocompatibility endpoints suggested by the FDA.
Chemical assessments
Because an understanding of all the chemicals that
could contact a patient during the use of a device is
critical to the evaluation of biocompatibility, a
chemical assessment of the device and its materials of
construction may be informative. This assessment may
be needed not only during initial development of the
device, but also upon any changes, such as
manufacturing process or material supply changes. An
OEM’s material supplier can support the OEM’s chemical
assessment in two ways:
• by providing information on chemical composition
• by providing guidance to ensure materials are
converted with minimal chance for degradation or
creation of unintended byproducts during the OEM’s
processing and sterilization cycles
For example, some thermoplastics contain chemical
building blocks that are susceptible to degradation
under extreme environmental conditions. The high heat,
temperature, and pressure of an autoclave can degrade
some thermoplastics and create potential for harmful
byproducts. So, even though the material coming from
the supplier passes all the biocompatibility testing,
the sterilization process should be carefully
considered to prevent creation of additional risk. |