Medical Design Briefs: 2022 Technology Leaders - 6

TECHNOLOGY LEADERS Test & Measurement
First, Do No Harm: Changing Strategies to
Prove Your Medical Device Is Safe
T
he Hippocratic Oath, attributed
to the Greek physician Hippocrates,
required doctors of the
time to " abstain from whatever is
deleterious and mischievous, " to " give
no deadly medicine, " and otherwise
avoid any voluntary act that may cause
harm. The maxim " first, do no harm " is
part of a broader set of commitments
that modern doctors promise, and all
who contribute to the art of healing
should abide.
Indeed, within the medical device
industry, we seek to enhance the lives of
patients through technology and design
and must never bring a device to market
that may do more harm than good.
There are many ways in which a medical
device could inadvertently cause harm,
confirming that a device doesn't cause
an unacceptable risk of harm amounts to
a demonstration of " biocompatibility. "
Verifying that a device is biocompatible
is a necessary burden. Of course,
devices are designed to be biocompatible,
but history has proven that unforeseen
complications or contaminants can
cause devastating harm.
As case studies rise to the surface
where people have been harmed, regulatory
scrutiny is renewed and the strategy
to prove biocompatibility changes. Prior
to the turn of the millennium, evaluation
was very much a check-box approach.
The G95 included a table of " Initial
Evaluation Tests for Consideration, " that
would inform the entire biological evaluation
plan. Knowing the contact type and
duration of contact, a manufacturer simply
ordered the required tests, and if
they all passed, the device was biocompatible.
The problem with check boxing
is that it required no knowledge of
device materials and any special risks
those materials would present. The outcome
was that very often burdensome
tests were executed and carried out
unnecessarily on materials certifiably biocompatible,
and other times materials
were used, like fishing line from the
sporting goods store, which could techni6
Biological
Evaluation
Plan (BEP): What are your
risks and how do you plan
to mitigate them?
Testing and risk
assessments
Biological Evaluation
Report (BER): Is the
device safe?
Fig. 1 - The Biological Evaluation Plan (BEP) has become the frontline vehicle to summarize testing and risks.
cally pass the test but do not belong permanently
in the body.
Therefore, ISO 10993-1 was drafted
and revised to insist on use of an intelligent
and risk-based approach. Knowledge
of the device materials and how
those materials may interact with the
body was made a prerequisite to conducting
animal tests. The FDA issued
guidance on application of a risk-based
and least-burdensome approach. Abandonment
of check-boxing necessitated
the formulation of strategies to effectively
evaluate biocompatibility: written documents
that lay out the materials, associated
risks, and how those risks would be
tested. The Biological Evaluation Plan
(BEP) has become the frontline vehicle
to summarize this information (see
Figure 1). Following formulation of the
BEP, tests and other scientific justifications
are made, and the results consolidated
and summarized in a capstone
story called the Biological Evaluation
Report (BER).
Regulatory expectations for the contents
and level of rigor in a BEP and BER
have rapidly been changing since the latest
update to ISO 10993-1:2018, ISO
10993-18:2020, and the European
Regulation 2017/745 (EU MDR). One
key requirement of 10993-1:2018 is that
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all devices, regardless of patient contact
or perceived risk, should have " physical
and/or chemical information. " While it
is explicitly clear that " physical and/or
chemical information " does not mean
chemistry testing, many device manufacturers
have pursued extractables chemistry
testing for the first time as a result
of this requirement.
Caution must be exercised in deciding
to do extractables testing, as not
every device type is amenable to such an
analysis, and there are examples where
generating extractables data can cause
more harm than good in a submission.
The first question should be whether
chemistry testing is truly necessary; if the
device is limited contact or resorbable,
other options should be explored first.
When chemistry testing is necessary, the
parameters must be perfectly clear and
checked against the most recent regulatory
expectation.
The requirements have shifted dramatically
over just a few short quarters.
Remember, the only reason to conduct
chemistry testing is to mitigate biological
risk that would otherwise require an
animal test. Therefore, the chemistry
results need to be reviewed by a toxicologist
who will make a claim regarding
safety. The parameters of testing must
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Medical Design Briefs: 2022 Technology Leaders

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