Medical devices can significantly improve
the health and well-being of the public.
Most medical device inventions start out
as a single great idea, but how does that great idea
become a marketed medical device?
This brief video will provide a basic overview of
medical device clinical trials or studies under
an Investigational Device Exemption,
more commonly referred to as an IDE.
It's one way an idea or a medical device invention
can be developed and make its way
to the U.S. medical device market.
What is a medical device?
The Federal Food, Drug, and Cosmetic Act
defines a medical device as a product intended for
the diagnosis, cure, mitigation, treatment,
or prevention of disease that does not achieve
its primary intended purpose through chemical interaction
and which is not dependent upon being metabolized.
Formal development of a medical device begins
during concept and design by establishing
mechanical, physical, and performance requirements.
We're gonna have to think about how this joins in.
Think of an architect who starts with a vision of
the design of a structure in their mind.
The architect may go through several different designs
trying to optimize different features with each version.
The architect's formal development process only begins
once the requirements are captured and translated
into the specifications for the final blueprint
of the building construction.
Similar to an architect's design of a structure,
the development of a medical device goes through
a formal development process.
The prototype for a medical device is typically developed
in a laboratory setting where access to the proper tools
and equipment can be provided.
Medical device design and development should follow
the traditional quality engineering development models
which have been adopted across many industries.
Once mechanical, stress, and other bench testing has been
completed on the prototype, many devices will be ready
for human studies.
Devices with new materials, ground-breaking technology,
or novel mechanisms may require
additional biocompatibility testing prior to human use.
Standards, available on the FDA website,
should be consulted when developing a medical device.
Before the medical device is tested in people,
the degree of risk of how the device
is used in the study must be determined.
The sponsor is a person or entity that initiates a study,
and they are responsible for making the initial
determination of which category the study falls into.
For device clinical research, there are three categories of
studies, each with specific regulations:
Significant Risk, or SR,
Non-Significant Risk, or NSR, and Exempt.
An SR device is defined as an investigational device
that presents a potential for serious risk to the health,
safety, or welfare of a subject.
For example, the device may be an implant
or used to support or sustain human life,
or the device may be of substantial importance in
diagnosing, curing, mitigating, or treating disease.
If a study is deemed SR, it must follow
all the IDE regulations in 21 CFR Part 812.
Otherwise, if it does not meet the definition of SR,
it may be NSR.
If it is NSR, then it would only have to comply with
the abbreviated IDE requirements in 21 CFR 812.2(b).
An investigational device study involving the lowest level
of risk may be considered exempt from 21 CFR Part 812.
The Institutional Review Board, or IRB, is the ethical body
which is required to oversee the conduct of clinical trials.
The job of the IRB is to ensure conformance to
the ethical principles of clinical research,
FDA regulations,
as well as other subject protection requirements.
Does this project qualify as exempt research since
the research will not involve interaction with subjects?
Remember, sponsors are responsible for making
the initial risk determination and presenting it to the IRB.
The subject should be contacted to seek informed consent.
The IRB, when presented with an NSR study,
must review the sponsor's risk determination
and change the determination
if the IRB disagrees with the sponsor.
FDA is available to help the IRB
when making its risk determination.
In addition to this initial review, the IRB also provides
continuing review of studies.
Both IRB and FDA approval must be obtained
before anyone can be enrolled as a subject in any SR study.
During the development of the device,
FDA is available to meet with sponsors.
At this meeting, sponsors have the opportunity, at no cost,
to discuss aspects of their submission, such as
study design, safety and effectiveness end-points,
timelines, et cetera.
Early interaction with the agency
should help to increase the sponsor's understanding of
FDA requirements, regulations, and guidance documents,
and will allow FDA personnel to familiarize themselves
with new technologies.
Increased interaction between FDA and sponsors should help
to speed the regulatory process and minimize delays
in the development of novel devices
intended for human use.
Sponsors need to submit a pre-IDE submission
to FDA to request a meeting.
Sponsors should carefully select clinical sites with
investigators who are qualified to perform the procedure,
if one is involved,
who are qualified to conduct FDA regulated research
and who have the ability to recruit eligible subjects.
For example, in an orthopedic implant study, a sponsor
would likely target orthopedic surgical sites,
as opposed to a general practice facility.
Comprehensive clinical site training is also critical prior
to subject enrollment to ensure that all site staff are aware
of the responsibilities associated with the study.
Can you breathe in?
The role and responsibility of a physician
is different from that of a clinical investigator.
For a physician, the primary objective
is optimal patient care.
On the other hand, the objective of
a clinical investigator is to protect human subjects
while following the protocol.
This allows information to be obtained that may improve
healthcare in the future.
Prior to enrolling a subject into a device study,
it is important that the clinical site staff
verify that the subject meets the eligibility criteria
and is properly consented.
Sign on the dotted line.
This means the subject has signed
an IRB-approved informed-consent document
prior to any study-related procedures being conducted.
This document outlines the potential risks, benefits,
and other critical information for the subject.
Tracking subject consent and enrollment is often
an important part of measuring a study's progress.
Under 21 CFR Part 812, sponsors are required
to adequately monitor their device study.
Through monitoring, which may be done as part of
an on-site review
or through remotely accessing the clinical data in real time,
sponsors can ensure that the right data
is being collected and the clinical investigator
is following the protocol.
If errors are identified as part of the monitoring effort,
it is important that the sponsor take swift action
to correct them and prevent any similar problems.
Once the study has been completed, it's important that
the sponsor properly close out the study by completing
the following steps:
Ensure that all subjects have completed
their follow-up medical procedures;
submit a final report to FDA,
ensure that all documentation is maintained
at all sites after the study has been completed,
and make certain that the site is ready for an FDA inspection.
Once all of the data from the clinical study have been
collected, it's important to make sure it's suitable
for statistical analysis.
After the sponsor believes their safety and effectiveness
end-points have been met and are statistically valid,
the sponsor can begin the process
of filing their marketing application
by discussing their submission with FDA.
After the sponsor submits their marketing application,
they should anticipate inspections by FDA.
These inspections can occur at manufacturing sites and
wherever the study records are stored, as well as
at clinical investigator sites where the research
was actually conducted.
What started out as a great idea became
an IDE making its way towards the medical device market.
The FDA likes to get involved early in this process,
which helps us fulfill our mission to protect
and promote public health.
It also helps us support medical device innovation
and the development of medical products
that satisfy unmet public health needs.