Overview of Exempt Medical Device Clinical Studies

May 15, 2016 - Lael Pickett; and Liz Scheurer, Principal Clinical Research Scientist, Neurocritical Care

The white paper “Overview of U.S. Medical Device Clinical Trials” provided a brief overview of US clinical studies regulations, the types of clinical studies and how to determine if an Investigational Device Exemptions (IDE) is required (Figure 1). This paper will focus on studies that are “Exempt” or rather, do not require an IDE application be filed with FDA for pre-study approval.

figure 1 us fda clinical study regulations by study type

US Food and Drug Administration (FDA) regulations in 21 CFR § 812.2(c) define what is considered to be an Exempt clinical study:

  • A device, other than a transitional device, in commercial distribution immediately before May 28, 1976, when used or investigated in accordance with the indications in labeling in effect at that time.
  • A device, other than a transitional device, introduced into commercial distribution on or after May 28, 1976, that FDA has determined to be substantially equivalent to a device in commercial distribution immediately before May 28, 1976, and that is used or investigated in accordance with the indications in the labeling FDA reviewed under subpart E of part 807 in determining substantial equivalence.
  • A diagnostic device, if the sponsor complies with applicable requirements in 809.10(c) and if the testing:
  • Is noninvasive,
  • Does not require an invasive sampling procedure that presents significant risk,
  • Does not by design or intention introduce energy into a subject, and
  • Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
  • Undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution, if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk.
  • A device intended solely for veterinary use.
  • A device shipped solely for research on or with laboratory animals and labeled in accordance with 812.5(c).
  • A custom device as defined in 812.3(b), unless the device is being used to determine safety or effectiveness for commercial distribution.

In general, Exempt studies consist of collecting long term patient outcome data on devices used in accordance with their labeling, consumer preference testing, testing of a device modification or testing of two or more commercial devices, if the testing does not collect safety or effectiveness data, or put subjects at risk.

The types of exempt devices defined in 21 CFR § 812.2 clearly provide sponsors with a sense that an Exempt study carries a much lower level of risk than studies that require an IDE application.

Note: Sponsor “means a person who initiates, but who does not actually conduct, the investigation, that is, the investigational device is administered, dispensed, or used under the immediate direction of another individual. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.”

Some “real-life” examples of Exempt studies include:

  1. Collecting information on medical devices that are used in accordance with their FDA cleared labeling, such as device registries (post market studies). Registry or retrospective studies that collect long-term patient data, e.g., pacemakers, for publication purposes are both examples of Exempt studies.
  2. A study testing consumer preferences or modification or a combination (but not determining safety or effectiveness), such as testing a thermometer with a smartphone interface.
  3. A study involving a diagnostic device e.g., evaluating a new skin patch thermometer for taking human body temperatures; where the temperature data collected will not be used to diagnose a subject.
  4. A Custom Device developed specifically for a patient, e.g. specialized orthopedic implant designed to replace a previously implanted orthopedic prosthesis and accommodate the patient’s anatomy.
  5. Medical devices used in veterinary research , which carry specific labeling requirements.

“CAUTION—Device for investigational use in laboratory animals or other tests that do not involve human subjects.”

While Exempt studies carry a lower risk profile and do not require an IDE, there are some elements of an IDE that do apply to the conduct of an Exempt clinical study. Specifically, the following regulations apply:

  • 21 CFR § 50- Protection of Human Subjects – All Exempt studies are required to provide informed consent to study participants. The Informed Consent Form (ICF) must contain all the required elements outlined in 21 CFR § 50.
  • 21 CFR § 54-Financial Disclosure of Clinical Investigators – All Exempt study Investigators are required to provide documentation that they do not carry a significant equity interest in the Sponsor’s company.
  • 21 CFR § 812.62-IRB Review – All Exempt studies must gain IRB (Institutional Review Board) approval of the Clinical Protocol and the ICF prior to study initiation. The IRB must also be in concurrence with the Sponsor that the study is considered “exempt” by federal definitions. If the IRB disagrees with the study type, the Sponsor may choose to reconsider the study design and resubmit the study to the appropriate branch of the FDA.
  • 21 CFR § 812.119 Disqualification of Clinical Investigators – All Exempt studies must ensure that they do involve investigators who have been disqualified by FDA.
  • 21 CFR § 812.150-Reports – Exempt studies are generally required to submit reports to any reviewing IRB.

FDA’s regulatory provisions for Exempt studies are meant to facilitate continued medical research that does not involve collection of medical safety and effectiveness data or put subjects at risk.

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