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6.2 Research Involving Investigational and Marketed Devices

Last Revised: 6/10/2026

For an abbreviated version intended for investigators, coordinators, and study teams - please visit here: Investigational and Marketed Devices

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for research involving investigational and marketed devices that are the objects of a clinical investigation.

2.0 Policy

It is the policy of the Organization that:

  • 2.1. The IRB will review all research involving devices in accordance with 21 CFR 50, 56; 21 CFR 812, 814; 45 CFR 46, and with HRPP policies.
  • 2.2. Investigators will conduct such research in accordance with the above cited regulations and applicable HRPP policies.
  • 2.3. Sponsors and any CRO acting on behalf of the sponsor will fully comply with FDA regulations at 21 CFR 812.

3.0 Definitions

  • 3.1. Device: an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is (a) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, OR (b) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, OR (c) intended to affect the structure or any function of the body of man or other animals, AND which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes (per section 201(h) of the FD&C Act).

    Note: FDA also defines certain software as a medical device if it is "intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device (software as a medical device, SaMD)" or software that is integral to a medical device (Software in a medical device)

  • 3.2. Investigational Device: a device, including a transitional device, which is the object of a clinical investigation (21 CFR 812(g)).

  • 3.3. In Vitro Diagnostic Devices (IVDDs): those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body (21 CFR 809.3).

    Note: an investigational IVDD is subject to FDA regulations at 21 CFR 812 and may require an IDE even if it is not the object of the clinical investigation (for example, if it is used to assess eligibility for an investigation).

  • 3.4. Clinical Investigation: research involving one or more subjects to determine the safety or effectiveness of a device (21 CFR 812.3(h)).

  • 3.5. Investigator: an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team (21 CFR 812.3(i)).

    Note: Per HRPP policy 1.26 (https://guides.unmc.edu/books/hrpp-policies-and-procedures/page/126-pi-qualifications-and-responsibilities) (PI Qualifications and Responsibilities), this individual is referred to as the Principal Investigator (PI).

  • 3.6. Subject: a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control. A subject may be in normal health or may have a medical condition or disease (21 CFR 812(p)).

  • 3.7. Significant risk (SR) device (per 21 CFR 812(m): a device that

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

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

    • 3.7.3. Is 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

    • 3.7.4. Otherwise presents a potential risk to the health, safety or welfare of a subject.

      Note: SR device studies must follow all the IDE regulations at 21 CFR 812, and must have an IDE application approved by FDA before they may proceed.

  • 3.8. Non-significant risk (NSR) device: a device that does not meet the definition of an SR device.

    Note: NSR device studies must follow the abbreviated requirements at 21 CFR 812.2(b). These abbreviated requirements address labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion. However, there is no need to make progress reports or final reports to FDA. NSR device studies do not have to have an IDE application approved by FDA.

    Note: FDA is the final arbiter as to whether a device study is SR or NSR and makes the determination when an IDE is submitted to FDA or if asked by the sponsor, clinical investigator, or IRB (per 21 CFR 812.2(b)).

  • 3.9. Investigational Device Exemption (IDE): an application submitted to FDA to conduct a clinical investigation with an investigational device that is subject to 21 CFR 812.2 and is classified as an SR device. An approved 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.

  • 3.10. Marketed Device: a device approved by FDA for marketing and is generally in use for treatment or diagnostic purposes.

    Note: When a marketed device is the object of a clinical investigation, it is subject to 21 CFR 812.2 unless it qualifies as an exempted investigation. IRB review and approval, however, is required.

  • 3.11. Sponsor: 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 (per 21 CFR 812(n)). The sponsor is responsible for complying with the requirements under FDA regulations at 21 CFR 812.40 through 47. The sponsor may be a device company, governmental agency, academic institution, private organization or an individual investigator.

  • 3.12. Sponsor-Investigator: an individual who both initiates and actually conducts an investigation, that is, under whose immediate direction the investigational device is administered, dispensed, or used (per 21 CFR 812(o)). An investigator who also serves as a sponsor must comply with all FDA requirements applicable to an investigator as well as a sponsor.

  • 3.13. Treatment Use of an Investigational Device: use of a device that is not approved for marketing, but may be under clinical investigation, for a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available. Under a treatment IDE, patients not in a clinical investigation may be treated utilizing the device in accordance with 21 CFR 812.36. IRB approval is required for treatment use of an investigational device.

  • 3.14. Emergency Use: use of a test article on a human patient in a life-threatening or severely debilitating circumstance where no standard medically acceptable treatment is available and there is not sufficient time to obtain full IRB approval for use of the test article to treat the patient.

  • 3.15. Unanticipated Adverse Device Effect (UADE): an adverse effect caused by, or associated with, a device, if that effect was (a) not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), and (b) the adverse effect relates to or impacts the rights, safety, or welfare of subjects (21 CFR 812(s)).

  • 3.16. A Custom Device (per 21 CFR 812.3(b) and section 520(b) of the Food Drug & Cosmetics Act): a device that (a) is not generally available to, or used by, other physicians or dentists; (b) is not generally available for purchase or dispensing upon prescription; (c) is not offered for commercial distribution; and (d) is intended for use by an individual patient, or to meet the needs of the individual physician or dentist.

4.0 Organization Responsibilities

  • 4.1. All contracts involving sponsored research conducted at UNMC/NM or CN (or affiliated clinics) where the investigational or marketed devices are the objects of the investigation will be negotiated in compliance with HRPP policy 1.12 (Sponsored Research).
    • 4.1.1. Contracts involving UNMC and/or NM faculty, staff and/or students will be negotiated by Sponsored Programs Administration (SPA) or by UNeHealth.
    • 4.1.2. Contracts involving Children’s Nebraska personnel who are not UNMC faculty, staff or students will be negotiated by CN Administration

5.0 IRB/ORA Responsibilities

  • 5.1. If the contract agreement requires compliance with ICH GCP, the IRB will review the submission in accordance with HRPP policy 1.13 (Compliance with ICH-GCP). The investigator will designate the need for ICH GCP compliance in the IRB application
  • 5.2. Prior to IRB approval of a clinical investigation involving investigational or marketed devices that are the objects of the investigation, the IRB will:
    • 5.2.1. ensure that a valid IDE is in effect for any device study subject to 21 CFR 812.2(a); or
    • 5.2.2. determine that the device is not a significant risk device, and ensure that the sponsor will comply with abbreviated requirements as described in 21 CFR 812.2(b); or
    • 5.2.3. ensure that the device is exempt from the requirements of an IDE (per 21 CFR 812.2(c)); specifically:
      • 5.2.3.1. A marketed device when used or investigated in accordance with the indications in labeling ; or
      • 5.2.3.2. A diagnostic device, if the testing (i) Is noninvasive, and (ii) does not require an invasive sampling procedure that presents significant risk, and (iii) does not by design or intention introduce energy into a subject, and (iv) Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure; or
      • 5.2.3.3. 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 subjects at risk; or
      • 5.2.3.4. A device intended solely for veterinary use, or shipped solely for research on or with laboratory animals; or
      • 5.2.3.5. A custom device, unless the device is being used to determine safety or effectiveness for commercial distribution.
  • 5.3. The determination that the device is not a significant risk device must be made by the convened IRB.
    • 5.3.1. the IRB will review the sponsor’s determination of the risk classification of the device and make a determination of risk based at least upon the following:
      • 5.3.1.1. The potential harm associated with the device itself
      • 5.3.1.2. The proposed use of the device
      • 5.3.1.3. Any procedure necessary for implantation of the device
      • 5.3.1.4. A comparison of the risks of the device against the risks of alternative devices or procedures.
    • 5.3.2. The IRB will document their determination of risk classification of the device and the rationale for the classification, and will inform the PI of the determination.
  • 5.4. Documentation of the IDE could be the industry sponsored protocol with the IDE number, written determination from the FDA, or other documentation or communication verifying the IDE number .

6.0 Investigator Responsibilities

  • 6.1. The Investigator must comply with all FDA regulations and additional responsibilities as described in the signed investigator statement (FDA form 1572), and per 21 CFR Parts 11, 50, 54, 56, and 812. These responsibilities include but are not limited to protecting the rights, safety, and welfare of subjects under the investigator’s care.
  • 6.2. The PI will ensure there are adequate controls in place for storage, security, and dispensing of investigational devices in accordance with 21 CFR 812.110.
  • 6.3. If a study involves an investigator-initiated IDE, the PI will comply with additional sponsor requirements per 21 CFR 812.40 and certify compliance by submitting Addendum P (Principal Investigator Responsibilities: Investigator-Initiated Device Trials).
  • 6.4. Any PI who has a study that will be audited by FDA must promptly notify IRB/ORA. The IRB/ORA must be provided with a copy of any findings resulting from that audit.
  • 6.5. Any PI who has a study that is undergoing a for-cause audit by the sponsor or CRO must promptly notify the IRB/ORA. The IRB/ORA must be provided with a copy of any findings resulting from that audit. Note that this does not include routine sponsor or CRO monitoring visits.
  • 6.6. The IRB/ORA must be provided with a copy of any findings resulting from an audit by the Fred & Pamela Buffett Cancer Center Protocol Review Monitoring System (PRMS) Audit Committee.

7.0 Expanded Access to Investigational Devices

Expanded Access to Investigational Device will be handled in accordance with HRPP policy 6.5 (Expanded Access to Investigational Drugs and Devices for Treatment Use).

8.0 Emergency Use of Investigational Devices

Emergency use of an investigational device will be administered to subjects in accordance with HRPP policy 6.4 (Emergency Use of a Test Article).

9.0 Waiver of Informed Consent for Planned Emergency Research

Waiver of informed consent for planned emergency research will be reviewed and approved by the full IRB in accordance with HRPP policy 5.6 (Exception from Informed Consent Requirements for Emergency Research).

DOCUMENT HISTORY:

 Written: 1/12/2016 - original author not recorded

 Revised: 3/2/2018 - revision not documented

 Revised: 5/6/2022 (Approved: 5/6/2022) - revision not documented

 Revised: 9/29/2022 - corrected typographic errors in section 4.2.

 Revised: 1/23/2024 – clarified IRB procedures (section 5.1); added definition of custome device, and included such devices as exempt from IDE requirements (sections 3.1.4 and 6.1.4).

 Revised 3/24/2026 – extensive stylistic revisions; added and modified definitions to accord with regulatory definitions; added appropriate regulatory citations; removed information present in other policies; removed information more appropriate in SOPs.

 Revised 6/10/2026 - Revised 6/10/2026 – added description of “software as a medical device” and “software in a medical device”; added definition of in vitro diagnostic device (IVDD); clarified that Children’s Nebraska Administration and not UNMC SPA or UNeHealth reviews clinical trial agreements or contracts involving Children’s Nebraska personnel who are not UNMC faculty, staff or students; clarified that the PI is responsible for ensuring that investigational devices are securely stored and dispensed in accordance with FDA regulations; other stylistic changes.

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