120. Investigational Device Research and Exempted Device Investigations

Updated June 29, 2021

For research involving medical devices, the University IRB will comply with the requirements set forth in 21 CFR Part 812. Per FDA regulations at 21 CFR 812, FDA’s regulations specify the circumstances under which either an IND (21 CFR 312) or an IDE (21 CFR 812) are required prior to conducting a clinical investigation. The Investigational Device Exemptions (IDE) regulations (21 CFR 812) describe three types of device studies: significant risk (SR), non-significant risk (NSR), and exempt studies.

Research to assess the safety or effectiveness of an investigational or unapproved medical device or a new indication for an FDA-approved device must:

have an FDA Investigational Device Exemption (IDE) (per 812.2, item (a));
be eligible for an Abbreviated IDE (per 812.2, item (b)) (see below for more information about Abbreviated IDE); or
be an exempted investigation (per (812.2, item (c)) (see below for more information about exempted device investigations).

An IDE permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device. (See IRB policy on overview of FDA regulations, information sheets and guidance for a listing of relevant references.)

NOTE: This policy addresses only those FDA regulations that are relevant to investigators and IRB review of research conducted under an IDE, Abbreviated IDE, or exemption from IDE requirements. It is not a comprehensive review of IDE regulations.

Individuals requiring additional information about IDEs are encouraged to review §812 Subpart B; §812 Subpart C; §812.119 (disqualification of a clinical investigator); FDA Guidance for IRBs, Clinical Investigators, and Sponsors: Frequently Asked Questions About Medical Devices; or contact Research Integrity.
Individuals interested in other uses of unapproved medical devices are encouraged to review IRB policy for information about Humanitarian Use Devices; and emergency, treatment, or continued uses of investigational devices.

Submission Requirements for Investigational Device Research

University/Affiliate investigators conducting device research must submit a device research application and the related documentation to provide the IRB with sufficient information to confirm the validity of the IDE, or to determine an Abbreviated IDE applies or the investigation is exempted. Investigators must complete the relevant section of the supplemental form entitled, “Research with Drugs, Biological Product, or Dietary Supplement, Blood or Specimen Collection, and Devices.” This form covers the type of IDE investigation requested, details about the device, device risks, and control of the device. Sponsors are responsible for making the initial risk determination and should provide the IRB with their risk assessment and the rationale used in making its SR or NSR determination. The IRB will confirm the validity of the IDE number by requiring that the investigator submit the notification of the IDE number assigned from the FDA, a letter from the sponsor, or the commercially or NIH-sponsored protocol containing the IDE number.

Significant Risk Devices

If the Sponsor or the FDA has already determined that the device is a significant risk device, the investigator must present evidence of an FDA approved IDE.

Non-Significant Risk Devices

An IDE is not required prior to IRB review and/or approval of a study of a NSR device, however the IRB must make a determination that the device is an NSR device.
1. In order to make a determination, the IRB will review the relevant information provided by the sponsor and investigator at a convened meeting. The required information includes a description of the device, reports of prior investigations conducted with the device, the proposed investigational plan, and subject selection criteria.
2. The IRB may agree or disagree with the sponsor's initial determination.
If the IRB determines the device is NSR, the IRB may approve the study using the criteria at 21 CFR 56.111. The study may begin without submission of an IDE application to FDA. The approved NSR device must comply with the abbreviated IDE requirements defined below:
1. The device is not a banned device.
2. The sponsor labels the device in accordance with 21 CFR §812.5.
3. The sponsor obtains IRB approval of the investigation after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device and maintains such approval.
4. The sponsor ensures that each investigator participating in an investigation of the device obtains, from each subject under the investigator’s care, consent under 21 CFR §50 and documents it, unless documentation is waived.
5. The sponsor complies with the requirements of 21 CFR §812.46 with respect to monitoring investigations;
6. The sponsor maintains the records required under 21 CFR §812.140(b) (4) and (5) and makes the reports required under 21 CFR §812.150(b) (1) through (3) and (5) through (10);
7. The sponsor ensures that participating investigators maintain the records required by 21 CFR §812.140(a)(3)(i) and make the reports required under §812.150(a) (1), (2), (5), and (7); and
8. The sponsor complies with the prohibitions in 21 CFR §812.7 against promotion and other practices.
The sponsor complies with the prohibitions in 21 CFR §812.7 against promotion and other practices. If an IRB determines that an investigation, presented for approval under 812.2(b)(1)(ii), involves a significant risk device, it shall so notify the investigator and, where appropriate, the sponsor. The study may not be approved until the investigator presents evidence of an FDA-approved IDE or the FDA makes a final determination that the device is NSR.

IRB Review of Investigational Device Research

The University requires Full Committee Review for investigational device research unless:

the research involves a nonsignificant risk device and is otherwise eligible for expedited review (per §56.111);
a continuing review package meets the DHHS (Common Rule) criteria for expedited review under Categories 8(a), 8(b), or 8(c); or
an amendment review package qualifies for expedited review (see the expedited review section in the IRB policy concerning overview of requirements for project amendments).

The IRB affirms validity of the IDE by matching the IDE number with information in the Sponsor protocol or through communication from the Sponsor or the FDA. When a University/Affiliate investigator holds the IDE, the IRB must be able to confirm the number matches information provided by the FDA.

In presenting a new investigational device research project to the IRB, the primary reviewer confirms:

the status for the IDE (i.e., valid IDE, Abbreviated IDE, or exempted investigation); and
the research complies with the additional FDA requirements for device research.

The IRB maintains records to document IRB activities regarding investigational device research as required at §56.115 (see IRB policy concerning IRB Records).

Requirements for Abbreviated IDE for Device Research

The University IRB complies with FDA regulations at §812.2, item (b) for categories of research that are considered to have an approved application for an IDE as an Abbreviated IDE.

Research conducted under an Abbreviated IDE must comply with the requirements for IRB review (at §56.111); informed consent (at §50.20); and documentation of consent unless the IRB waives the requirement for participants to sign a written consent form in accordance with regulations at §56.109, item (c).
For research to be conducted under an Abbreviated IDE, the investigational device cannot be a banned device.
For research to be conducted under an Abbreviated IDE requires IRB determination of Significant Risk Device (see online Policy Manual Definitions) or nonsignificant risk device as evidenced by documentation from the sponsor, device manufacturer, or FDA.
Investigators must confirm the sponsor complied with FDA regulations for device labeling (at §812.5) (see requirements for device labeling below).
Investigators must comply with requirements for monitoring investigations as codified at §812.46 (see requirements for monitoring device investigations below).
Investigators must agree to maintain accurate, complete, and current study records as required under §812.140, item (a) (see requirements for record-keeping below); and comply with reporting requirements at §812.150, item (a) (see reporting requirements below).
Investigators and sponsors must comply with the prohibitions at §812.7 against promotion and other practices involving investigational devices.

NOTE: The IRB may require documentation from the investigator or FDA to confirm that all Abbreviated IDE requirements have been satisfied.

IRB Assessment for Significant Risk Device (Required for Abbreviated IDE)

Investigators planning to conduct research under an Abbreviated IDE must provide the IRB with documentation from the FDA, study sponsor, or device manufacturer relevant to an IRB determination of significant risk device (see Policy Manual Definitions) or nonsignificant risk device. (See FDA information sheet guidance: Significant Risk and Nonsignificant Risk Medical Device Studies for more information and a list of nonsignificant risk devices.)

The IRB may consult with or request documentation from FDA for significant or nonsignificant risk determinations for investigational device research. If FDA has already made a significant or nonsignificant device risk determination for the study, the agency's determination is final (i.e., supersedes that of the IRB).

The IRB reviews information in the protocol application, device instruction manual and labeling, and investigator brochure (as applicable) related to descriptions of the device and its proposed use; the nature and seriousness of the harm that may result from the use of the device or from procedures required for use of the device (e.g., surgical implants); reports of prior investigations conducted with the device; participant selection criteria, and safety monitoring procedures. The IRB considers the following questions when assessing for significant risk device research:

Is the device intended as an implant and does that use present a potential for serious risk to the health, safety, or welfare of participants?
Is the device purported or represented to be for a use in supporting or sustaining human life and does that use present a potential for serious risk to the health, safety, or welfare of participants?
Is the device for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and does that use present a potential for serious risk to the health, safety, or welfare of participants?
Does the device otherwise present a potential for serious risk to the health, safety, or welfare of a participant?

A determination of nonsignificant device research is NOT the same as a determination of minimal risk for human research.

Nonsignificant risk device research conducted by University/Affiliate investigators under an Abbreviated IDE may start as soon as the IRB reviews and approves the study. Prior FDA approval for such studies is not required.

If the IRB makes a determination of significant risk device, the IRB will notify the investigator in writing of its determination and will require resubmission and review of the research under an IDE.

The IRB documents determinations of significant or nonsignificant device research and justification for same in meeting minutes.

Exempted Device Investigations

According to FDA regulations at §812.2, item (c) the following types of devices are exempted from requirements for IDE, even when the purpose of the investigation is to assess the safety or effectiveness of an investigational device in humans:

The device is other than a transitional device and was in commercial distribution immediately before May 28, 1976; and is used or investigated according to the indications in labeling in effect at that time.
The device is other than a transitional device and was introduced into commercial distribution on or after May 28, 1976; FDA determined the device is substantially equivalent (under Subpart E of §807) to a device in commercial distribution immediately before May 28, 1976; and the device is used or investigated according to the indications in the labeling reviewed by FDA in determining substantial equivalence.
A diagnostic device if the sponsor complies with the requirements for labeling in vitro diagnostic products as “for research” or “for investigational” use only (per §809.10, item (c)); 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 participant; and the device is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
A device 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 participants at risk.
A custom device (see online Policy Manual Definitions) that is not being used to determine safety or effectiveness for commercial distribution.

The IRB is not required to assess for significant risk devices in exempted investigations.

Exempted investigations must comply with the requirements for IRB review and informed consent (at §56.111 and §50.20, respectively).

Additional FDA Requirements for Investigational Device Research

FDA Requirements for Device Labeling

Investigators and the IRB are responsible for ensuring investigational devices comply with FDA requirements for device labeling at §812.5. Specifically, the package labeling must:

NOT represent the device as safe or effective;
provide the name and place of business of the device manufacturer; packer, or distributor; quantity of package contents; and the statement “CAUTION—investigational device. limited by Federal (or United States) law to investigational use;” and
note relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions related to use of the device.

FDA Prohibitions Against Promotion and Other Practices for Investigational Devices

Investigators must provide the IRB with sufficient information to assess compliance with FDA prohibitions against promotion of investigational devices (at §812.7). Specifically, neither investigators nor sponsors may:

promote or test market an investigational device until after FDA has approved the device for commercial distribution;
commercialize an investigational device by charging the participants or investigators for a device a price larger than that necessary to recover costs of manufacture, research, development, and handling;
unduly prolong an investigation; or
represent that an investigational device is safe or effective for the purposes for which it is being investigated.

FDA Requirements for Importing/Exporting Investigational Devices

When applicable, the IRB considers the additional FDA requirements for import/export requirements for device research as codified at §812.18.

FDA Requirements for Emergency or Treatment Uses of Investigational Devices

FDA regulations at §812.36 provide general information and criteria for use of an unapproved device (including those under clinical investigation) for treatment of a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available.

IRB policy describes the requirements for physicians and the IRB for emergency or treatment (compassionate) uses of investigational devices.

FDA Requirements for Monitoring Investigational Device Research

Investigators must provide the IRB with sufficient information to assess compliance with FDA requirements for monitoring investigations (at §812.46). Specifically, investigators must submit for IRB review:

a copy of the signed agreement between the investigator and the sponsor;
the investigational plan for use of the device; and
sponsor requirements for disposing or returning the device following termination of an investigator’s participation in the investigation.

Investigators must comply with any post-approval conditions required for IRB approval (as specified in the approval letter).

Investigators Responsibilities for Device Investigations

Related to the conduct of device investigations, per §812, Subpart E, investigators are responsible for:

conducting the investigation according to the signed agreement with the sponsor, the investigational plan, applicable FDA regulations (as addressed in this policy), and any additional requirements from the IRB or FDA;
protecting the rights/welfare of participants under their care;
ensuring written informed consent is obtained from all prospective participants prior to their participation in the investigation; and
establishing controls for handing the device that ensure the investigational device is only used with participants under the investigator’s supervision and the device is not supplied to any person not authorized to receive it.

Following completion or termination of the device investigation or her/his part in same, investigators must dispose of or return the device as required by the sponsor.

University/Affiliate investigators conducting research involving investigational devices must complete the supplemental form for devices. The form requires investigators to describe how they will maintain control of the device during and after the investigation. The IRB may request additional documentation from the performance site to assess the investigator’s control of investigational devices.

FDA Requirements for Record-Keeping for Investigational Device Research

Investigators must agree to maintain accurate, complete, and current study records as required under §812.140, item (a). Specifically, investigators must maintain:

all correspondence with another investigator, an IRB, the sponsor, a monitor, or FDA;
all required reports (see reporting requirements above;
records of receipt, use, or disposition of the device including (i) the type and quantity of the device, the dates of its receipt, and the batch number or code mark; (ii) the names of all persons who received, used, or disposed of each device; and (iii) why and how many units of the device were returned to the sponsor, repaired, or otherwise disposed of;
records of each participant’s case history and exposure to the device including case report forms, signed and dated consent forms, and medical records related to use of the device;
documentation confirming informed consent was obtained prior to participation in the study, or for any use of a device by the investigator without informed consent, the required written concurrence of a licensed physician and written justification for using the device without obtaining and documenting informed consent;
records of adverse device effects (whether anticipated or unanticipated);
records describing the condition of each participant upon entering and during the course of the investigation, including relevant previous medical history and the results of all diagnostic tests;
records documenting the exposure of each participant to the investigational device, including the date and time of each use, and any other therapy;
documentation of dates and reasons for deviation from the approved investigational plan; and
any other records required by FDA as communicated to the investigator by the sponsor.

FDA Reporting Requirements for Investigators Conducting Investigational Device Research

Investigators must comply with FDA reporting requirements as codified at §812.150, item (a)). Specifically, investigators must:

report unanticipated adverse device effects to the sponsor no later than 10 business days of learning of the effect, and the IRB according to the IRB policy for reporting problems;
report the withdrawal of approval by the University IRB to the sponsor within 5 working days of the withdrawal;
submit progress reports on the investigation to the sponsor and the monitor as specified in the sponsor agreement or investigational plan, and the reviewing IRB as specified in the IRB approval letter;
notify the sponsor and the University IRB of deviations from the investigational plan which are necessary to protect the life or physical well-being of a participant in an emergency as soon as possible, but no later than 5 working days after the emergency occurred (per IRB policy for reporting problems);
report any uses a device without prior informed consent to the sponsor and the University IRB within 5 working days of the device use;
submit a final report to the sponsor and the reviewing IRB within 3 months after termination or completion of the investigation or the investigator's part of the investigation; and
provide any other reports/information requested by the sponsor, the University IRB, or FDA.

FDA Inspections for Investigational Device Research

Investigators and the IRB must comply with FDA requests for inspections related to investigational device research as codified at §812.145. Specifically, those with the authority to grant access must allow authorized FDA employees, at reasonable times and in a reasonable manner, to:

enter and inspect locations where devices are held, installed, used, or implanted;
enter and inspect locations where records of results from use of devices are kept; and
inspect and copy all records relating to an investigation.

Under the following two conditions, investigators must permit authorized FDA employees to inspect and copy records that identify participants:

FDA has reason to suspect that adequate informed consent was not obtained;
FDA has reason to suspect that reports from the investigator, sponsor, or the IRB were not submitted or are incomplete, inaccurate, false, or misleading.