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Demystifying The Investigational Device Exemption Process – Life Sciences, Biotechnology & Nanotechnology


The FDA regulatory gauntlet can be a daunting challenge.

That’s especially true for startups new to the field. But it
need not be. The process serves an important purpose—ensuring
that new drugs and medical devices marketed to the public are safe,
effective, and result in the intended health outcomes.

That’s why in my 30 years of advising tech and life sciences
companies, I often have to remind eager entrepreneurs of this:

Having great science is not enough.

The pathway for getting a product to market
does require great science, but that science must
also be grounded in a practical understanding of what it takes to
clear Food and Drug Administration (FDA) requirements. In the case
of a new medical device, this includes navigating the premarket
approval (PMA) or 510(k) process.

In short, the PMA process (or the 510(k) for devices that are
deemed “substantially equivalent” to an already approved
device) provides the FDA the information it needs to determine if a
medical device is safe, effective, and ready to market to the
public. In most cases, a device sponsor will also need to first
conduct clinical studies in support of its PMA or 510(k)
application. To conduct these clinical studies, a sponsor must
first submit an investigational device exemption application or

The IDE process is designed to ensure that a clinical study is
well-designed, that the anticipated benefits outweigh the potential
risks to human subjects, and that appropriate safeguards are in
place to minimize those risks. As such, successfully navigating the
IDE process is a critical frontrunner to receiving PMA or 510(k)


What is an IDE and when do you need one?

Medical devices vary widely and so too do the regulations
regarding their testing.

For example, a tongue depressor is minimally invasive and low
risk, so it requires much less stringent pre-marketing and testing
approval requirements than a pacemaker or artificial organ. The
regulatory scheme appreciates this variability by providing
different pathways for approval depending on the relative risk
posed by the intended use of a particular device.

Class I devices present the lowest risk and are
subject to general controls but are generally exempt from FDA
approval and premarket notification requirements. Manufacturers
must still comply with baseline general controls including
registration, manufacturing, labeling and device listing

Class II devices present a moderate risk of
harm and while still subject to the same general controls as Class
I devices, may also require 510(k) approval from the FDA before
marketing. The 510(k)-approval process is designed to determine
whether the device is substantially equivalent to an already
approved predicate device. While clinical data, and consequently an
IDE, is not typically required for most 510(k) applications, a
small percentage of applications do require clinical testing and an

Class III devices present the highest risk and
generally require a premarket notification (PMN) approval from the
FDA before marketing. Class III devices typically require evidence
from animal studies and clinical trials to judge the relative
safety and effectiveness of the device. Consequently, most Class
III devices will require IDE approval.

Still, not all Class III devices require an IDE prior to
clinical studies. The need for and level of FDA review and approval
required to conduct a clinical study largely depends on the level
of risk posed by the proposed clinical trials.

Exempt and Diagnostic Device Studies

As the name implies, exempt device studies require no federal
filings or additional FDA approval prior to conducting a clinical
study. Exempt devices generally include:

  1. Those already in use in a manner that is consistent with their
    labeled use;

  2. One that is substantially equivalent to another device already
    in distribution;

  3. A device being studied for consumer preference, veterinary use,
    research in laboratory animals, and customary devices, and;

  4. Non-invasive diagnostic devices that do not present a
    significant risk to humans.

Non-Significant Risk Devices

Non-significant risk (NSR) devices require filing an abbreviated
IDE but do not require FDA approval. The sponsor must only receive
approval from the reviewing institutional review board (IRB) at
each institution where the investigation is being conducted. If the
IRB considers the device to pose a significant risk, it must report
this to the FDA and the sponsor must receive FDA IDE approval
before commencing any studies.

Significant Risk Devices

A medical device that is deemed by the sponsor or IRB to pose a
significant risk must file an IDE and obtain approval from the FDA
before beginning clinical studies. FDA regulations define a significant risk (SR)
device as one that is

  • intended as an implant and presents a potential for serious
    risk to the health, safety or welfare of a subject;

  • purported or represented to be for use supporting or sustaining
    human life and presents a potential for serious risk to the health,
    safety, or welfare of a subject;

  • for a use of substantial importance in diagnosing, curing,
    mitigating, or treating disease or otherwise preventing impairment
    of human health and presents a potential for serious risk to the
    health, safety or welfare of a subject;

  • or otherwise presents a potential for serious risk to the
    health, safety or welfare of a subject.” The FDA provides
    additional guidance on determining a device’s risk
    classification. Notably, a device that is otherwise considered to
    pose a nonsignificant risk may fall in the significant risk
    category if its proposed use presents a novel significant risk,
    such as by increasing surgery time or when used in combination with
    another device that increases the risk.


The IDE Application

There is no standardized form for the IDE application, but the FDA
has issued helpful guidance that details what information should
be included. The FDA has 30 days to approve or disapprove the
application. Along with a cover letter, the application should

  • Prior investigations, including prior clinical and other
    testing and any adverse information

  • Manufacturing information about the quality control of the

  • Investigator information and commitment statement

  • Institutional review board information

  • Device sale and labeling details

  • Informed consent materials for use in clinical trials

  • Any other relevant materials

In addition, the IDE must include information about the
investigational plan, including:

  • A detailed description of the device, name and objectives of
    the study

  • The study protocol, including a description of its methodology,
    study subjects, study endpoints, endpoint assessment methods and
    adverse event definition

  • Risk analysis and justification of the relative risk to
    subjects along with an explanation of how risks will be

  • A detailed device description and anticipated device changes
    during the investigation

  • Description of the monitoring process and contact information
    of monitors

  • Additional records and reports that may be required

Getting Early Feedback

The FDA has established several pathways by which medical device
sponsors can engage in early conversation and receive helpful
feedback about the PMA, 510(k), and IDE process. Early interaction
opportunities with the FDA should be used to the greatest extent
possible. Doing so can improve the quality of IDE submissions,
shorten review times and streamline the development process.

Study Risk Determination Meetings

Study risk determinations can be requested to receive FDA
guidance on whether a proposed study is exempt or considered a
significant or non-significant risk for the purposes of requiring
an IDE. The FDA provides detailed guidance on risk determination
and meeting availability here.

Informational Meetings

Informational meetings may be appropriate where a sponsor wants
to familiarize the FDA with a new device or to provide an overview
of device development when multiple submissions may be planned in
the coming year. The FDA does not give feedback in an informational
meeting. If a sponsor wants to receive FDA feedback, they should
utilize the pre-submission or early collaboration meeting


The FDA encourages new sponsors or those who are proposing
studies with new technologies or new uses for existing technologies
to utilize the pre-submission process. The pre-submission process
provides an opportunity for the sponsor to request and receive
formal feedback on its IDE request from the FDA in writing or via a
telephonic or in-person meeting.

Formal Early Collaboration Meetings

Formal early collaboration meetings provide an opportunity for
the agency to provide early feedback to sponsors on the proposed
bench/animal testing and clinical trial design. An informal version
of this process was once referred to as a “pre-IDE”
meeting but has more recently been formalized under the FDA
Modernization Act (FDAMA). Under the new formal meeting
regulations, any advice given must be in writing and is generally
binding on the agency.

Two types of formal early collaboration meetings can be

1. Determination Meeting

A determination meeting may be appropriate for sponsors
anticipating submitting a PMA. The meeting can help the sponsor
better understand what type of evidence will be necessary to
demonstrate device effectiveness and whether clinical studies are
needed. The FDA will also work with the applicant to determine the
least-burdensome way to evaluate the device’s effectiveness and
that also has a reasonable likelihood of success.

2. Agreement Meeting

An agreement meeting is available to sponsors investigating a
class III device and who intend to submit a 510(k) request. The
purpose of the meeting is to agree on clinical protocol and other
key parameters of the investigational plan.

The Pathway to IDE Success

The IDE is a critical step in new device development and
requires careful and informed planning. Utilizing early
communication channels with the FDA can help you secure IDE
approval and ultimately smooth the pathway to market. Approaching
the agency with a spirit of cooperation and transparency is
paramount. It will help establish trust and reveal potential
concerns at an early stage when it’s more likely they can still
be easily remedied.

An experienced consultant can help you successfully navigate the
IDE process and set the foundation for PMA and 510(k) success. Crowley Law LLC is a full-service law firm for
tech and life science companies with an extensive network of
experienced FDA consultants with whom we can work to optimize your
overall business, legal and regulatory strategy.

Originally published 8.4.21

The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.


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