Medical Design Briefs - April 2021 - 8

EUA Devices

must be submerged into the extraction
solvent, thereby exposing materials that
may not actually contact the patient to
the solvent. Another difficulty is solvent
selection for extraction. Would chemical characterization of the materials
using strong, nonclinically relevant solvents correctly assess a patients' potential risk, or would doing such work
merely provide erroneous data that
incites more chemistry work and would
therefore prevent necessary devices
from coming to market?
Toxicological Assessment. Solvent
selection has been a hot button topic for
all devices in extractables and leachables
testing for quite some time, and breathing gas pathway devices have just furthered that discussion. With breathing
gas pathway devices, water is typically
used along with a secondary, semi, or
nonpolar solvent. With water, the assessment is more straightforward as water is
clinically relevant (as a simulant for
humidified air). Other solvents prove to
be difficult, as none of these devices are
intended to be in contact with harsher
semi and nonpolar solvents. As with the
air VOCs and particulates discussion,
extracting only the interior of the device
in solvent is more problematic, since the
ends of tubing or face masks cannot be
blocked off to prevent solvent from
escaping. This means that the whole
device must be submerged in the extraction solvent, and an extrapolation from
total surface area to interior surface area
must be made to assess the clinically relevant concentration of the compounds
that are detected.
More often than not, the adjusted
data is not clinically relevant because it
assumes that the total amount of solvent used for the extraction will be
exposed to the patient. Often the volume of solvent used for extraction is in
the 0.5-2.0-L range. But if clinical practices are considered, the amount of liquid that could potentially reach a patient is only the liquid condensation
forming on the interior of the device
tubing. A logical estimation for that
volume of liquid is orders of magnitude below the volume of liquid used
in the extraction testing. Understanding these challenges is key to properly
testing and assessing these devices.
Using this condensate example, there
are ways to address this gap between
how the device was tested and how the

data can then be assessed to ensure
patient safety. One way is to adjust the
amount of extractable concentrations,
which can be done in two ways - surface area or condensate volume - as
discussed below.
The concentration of extractable compounds can be adjusted through consideration of the surface area extracted.
The interior of the device is compared to
the total surface area that was extracted
to model the potential patient exposure
concentrations against the total concentrations that were extracted. This
method can often decrease the concentration of the extractable compounds by
approximately 50 percent, if the exterior
and interior are similar in surface area.
However, this still is not an accurate
approximation to the actual patient
exposure.
A more accurate way to adjust the
amount of extractable concentrations is
to assess for a condensate volume.
However, to do this, the amount of condensate needs to be determined. There
are a couple of ways this can be accomplished, with the more common way
being via gravimetric analysis. The
device is run through a simulated test
cycle with maximum humidification to
determine the amount of water mass
that can collect in the tubing. The
device is weighed before and after the
simulation, with the difference in
weight being the amount of water condensate that has collected in the tubing
during the simulation. A second option
is to conduct a similar study but instead
of a gravimetric weight determination,
a drip chamber is used. The amount of
water that collects in the drip chamber
is assumed to be the maximum amount
of condensate that could contact the
patient. In using either measuring
method, the concentration of extractables present is then decreased by the
ratio of solvent volume in the extraction, to the total condensate volume
that was determined.
Face Masks
Face masks are also an important
aspect in the support of controlling the
spread of COVID-19. While some testing was able to be addressed through
justification for EUA approval, it is suggested that assessment for cytotoxicity,
sensitization, and irritation be considered when assessing the safety of facial

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masks. There is a plethora of clinical
data available to support that the
masks, in general, are safe. When considering the biological approach to be
taken for masks, it would be good to
consider the draft guidance released
from FDA in October 2020, " Certain
Devices in Contact with Intact Skin. "
This guidance, when fully approved,
will allow for simpler justification of
intact skin-contacting devices made
from common materials with a history
of safe use (i.e., polyester and cotton).
One of the tests that can be problematic is cytotoxicity.
Many of the ear bands demonstrate
a cytotoxic reaction due to the elastomeric content of the bands themselves. Options to address this outcome include to test the components
of the mask individually or to perform
a dilution series through a comparative study to show similar cytotoxicity
to a face mask already approved and
on the market.
Toxicological Assessment. The rationale for these approaches can be made
in a toxicological risk assessment
(TRA), which outlines how to assess the
device in a way that accurately reflects
the intended use and clinical application of the device. In the TRA, the
aforementioned adjustments are used
to understand what the clinically relevant exposure concentrations are and
how to ultimately reduce any possible
hazardous risks to the patients. These
assessments must be completed using
the best scientific thought, logical practices, and reasonings available to correctly ascertain any risk posed to the
patient.
When presenting these arguments to
any regulatory agency, it is imperative
for both the composer of the risk assessment and the reviewer to use not only
knowledge of the current standards,
but also to understand the arguments
and scientific reasoning used to assess
the device and ensure patient safety. It
is our duty, as engineers, scientists, and
toxicologists to provide the best options
available to patients and avoid getting
caught up in a strict approach to testing
in place of scientific reasonings.
This article was written by Christopher
Pohl, Associate Toxicologist, Nelson Laboratories, LLC, Salt Lake City, UT. For more
information, visit http://info.hotims.com/
79412-340.
Medical Design Briefs, April 2021

http://info.hotims.com/79412-340 http://www.medicaldesignbriefs.com

Medical Design Briefs - April 2021

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