6.2 Research Involving Investigational and Marketed Devices

Last Revised: 1/23/2024

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

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2.0 Policy

2.1.

It is the policy of the Organization thatthat:

the

2.1. The IRB will review all research involving investigational devices and FDA-approved devices (test articles) in full accordance with the following: 21 CFR 50, 56; 21 CFR 812, 814; 45 CFR 46.46, and with HRPP policies. 2.2. It is the policy of the Organization that investigatorsInvestigators will conduct such research in full accordance with the above cited regulations and applicable HRPP policies. 2.3. It is the policy of the Organization that sponsorsSponsors and any CRO acting on behalf of the sponsor will fully comply with FDA regulations at 21 CFR 812.

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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 meansDevice: a device, including a transitional device, which is the object of a clinical investigation. As further defined, a device is any healthcare product that does not achieve its primary intended purpose by chemical action or by being metabolized.

3.2. Clinical Investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA under Section 505(i) or 520(g) of the Act or need not meet the requirements for prior submission to the FDA under these sections of the Act but the results of which are intended to be later submitted as part of an application for a research or marketing permit. The terms research, clinical research, clinical study, and clinical investigation are(21 deemedCFR to be synonymous.812(g)).

3.3. InvestigatorIn meansVitro 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 whichwhose immediate direction the test article is administered or disperseddispensed toto, or used involving, a subject.subject, Underor, 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 PI.Principal Investigator (PI).

3.4.6. HumanSubject: Subjecta meanshuman who participates in an investigation, either as an individual whoon whom or on whose specimen an investigational device is or becomes a participant in a clinical investigation either as a recipient of the test articleused or as a control. A subject may be eitherin normal health or may have a patientmedical condition or adisease healthy(21 individual.CFR 812(p)).

3.5.7. Significant risk (SR) device (SRD)per is21 CFR 812(m): a device that

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

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

• 3.5.7.3. 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

• 3.5.7.4. 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.

3.6.8. Non-significant risk device(NSR) (NSRD) isdevice: a device that does not meet the definition of an SRD.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.IRB See(per 21 CFR § 812.2(b)(1)).

3.7.9. Investigational New Device Exemption (IDE) is: 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 SRD.SR Thedevice. An approved IDE is submitted by the sponsor of the research. The FDA will providepermits a writtendevice authorizationthat otherwise would be required to conductcomply with a clinicalperformance investigationstandard within 30 days after receipt of the IDE. If the device is not an SRD, the investigation is considered by FDAor to have anpremarket approvedapproval IDEto unlessbe FDAshipped notifieslawfully for the sponsorpurpose otherwise.of conducting investigations of that device.

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

Note: When a marketed device is usedthe inobject 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.

3.9.11. SponsorSponsor: is thea person who initiates, but who does not actually conductconduct, the investigation.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 812.40-40 through 47. The sponsor may be a device company, governmental agency, academic institution, private organization or an individual investigator.

3.10.12. Sponsor-Investigator isInvestigator: an individual thatwho both initiates and actually conducts an investigation, that is, under whose immediate direction the investigational device is administered, dispenseddispensed, or used.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.

3.11.13. Treatment Use of an Investigational Device meansDevice: use of a device that is not approved for marketing, but may be under clinical investigational,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.

3.12.14. Emergency Use meansUse: 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.

3.13.15. Unanticipated Adverse Device Effect (UADE) means: an adverse effect caused by, or associated with, a device, if that effect was:was 1)(a) not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), and 2)(b) the adverse effect relates to or impacts the rights, safety, or welfare of subjects.subjects (21 CFR 812(s)).

3.14.16. A Custom Device (as defined inper 21 CFR 812.3(b) and section 520(b) of the FFDA)Food meansDrug & Cosmetics Act): a device that meets all of the following criteria:

It is necessarily different from generally available devices or performance standards to meet the order of an individual physician or dentist;

(a) It is not generally available to, or used by, other physicians or dentists;

(b) It is not generally available for purchase or dispensing upon prescription;

(c) It is not offered for commercial distribution;

and (d) It is intended for use by an individual patient, or to meet the needs of the individual physician or dentist.

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4.0 RequirementsOrganization Responsibilities

• 4.1. All contracts betweeninvolving sponsorssponsored andresearch UNMC,conducted Nebraskaat Medicine,UNMC/NM andor BMCCN for(or affiliated clinics) where the investigational deviceor studiesmarketed mustdevices are the objects of the investigation will be reviewed and approved by UNMC Sponsored Programs Administration (SPA) or by UNeHealth, in compliance with HRPP policy 1.12 (Sponsored Research).

4.2. All contracts between sponsors and CHMC for investigational device studies must be reviewed and approved by UNMC Sponsored Programs Administration (SPA) or by UNeHealth, or by CHMC Administration,negotiated in compliance with HRPP policy 1.12 (Sponsored Research). If

the4.1.1. contractContracts isinvolving reviewedUNMC andand/or approvedNM faculty, staff and/or students will be negotiated by CHMCSponsored Programs Administration it(SPA) will also be reviewedor by UNMC SPA or UNeHealth to assure the requirements of HRPP policy 1.12, section 4.3 are met.UNeHealth. 4.3.1.2. Clinical investigationsContracts involving SRChildren’s devicesNebraska mustpersonnel who are not UNMC faculty, staff or students will be reviewed and approvednegotiated by theCN full IRB in accordance with HRPP policy 2.2 (Full IRB Review). However, the IRB may determine select clinical investigations involving NSR devices and exempt devices that are no more than minimal risk may be eligible for expedited review in accordance with HRPP policy 2.3 (Expedited Review).Administration

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5.0 IRB/ORA Responsibilities

4.4.5.1. 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.application 4.5.2. IfPrior to IRB approval of a studyclinical involvesinvestigation aninvolving investigator-initiatedinvestigational IDE,or itmarketed isdevices that are the expectationobjects of the Organization that the PI will also comply with the FDA-mandated sponsor requirements (21 CFR 812) and certify compliance by submitting Addendum P (Principal Investigator Responsibilities: Investigator-Initiated Device Trials) which specifies all of the responsibilities of the Sponsor-Investigator. 4.6. Any PI who has a study that is audited by the sponsor, a CRO or FDA must immediately notify the UNMC Chief Compliance Officer and provideinvestigation, the IRB with a copy of the report following the audit. When the study is audited by the Fred & Pamela Buffett Cancer Center Protocol Review Monitoring System (PRMS) Audit Committee, a copy of the report must be provided to the IRB. 4.7. If a study involves an investigator-initiated IDE, the PI must also comply with the FDA-mandated sponsor requirements.

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5.0 IRB Procedures

will:

• 5.2.1. The IRB will review information in the application to ensure that (1)a thevalid IDE is in effect for any device hasstudy ansubject IDEto issued21 byCFR the FDA,812.2(a); or

satisfies5.2.2. thedetermine requirements for exemption from IDE; and (2)that the device is not a bannedsignificant device.risk device,

5.2. The IRB will review the information in the application toand ensure that the PIsponsor haswill adequatecomply controlswith abbreviated requirements as described in place for storage, security, and dispensing of investigational devices in accordance with 21 CFR 812.110. The IRB will assess whether:

5.2.1. The device is stored and secured in a manner that restricts access to investigators. As appropriate this may be a cabinet that has a physical lock to which only an investigator has a key (physical2(b); or electronic), or some other equivalent process. 5.2.2. The device is dispensed in a manner that assures that only subjects who have provided informed consent will be treated or tested/examined using the investigational device. This should involve marking the device in an easily visible manner that it is for investigational use only, and, as appropriate, include a mechanism to have a second party review the signed consent form prior to dispensing the device from a storage location, or some other equivalent process. 5.2.3. The investigator and the departments, sections, or operating rooms where device is used maintains records sufficient to documentensure that the storage, security and dispensing of investigational devices has been in accordance with 21 CFR 812.110. These records may be physical or electronic, as long as they satisfy the requirements of 21 CFR 812.140, including, but limited to records of receipt, use or disposition of a device that relate to: (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 have been returned to the sponsor, repaired, or otherwise disposed of.

5.3. Unless the research is exempt from the FDA IDE regulations, the IRB will review the sponsor’s determination of the risk classification of the device (SR or NSR) and make a determination of risk based upon the following:

5.3.1. The potential harm associated with the device itself 5.3.2. The proposed use of the device 5.3.3. Any procedure necessary for implantation of the device 5.3.4. A comparison of the risks of the device against the risks of alternative devices or procedures.

5.4. The IRBs determination of risk classification of the device and the rationale for the classification will be documented in the IRB minutes.

5.5. If the IRB has any question or concern about whether a study is SR and, therefore, requires an IDE, the PI will be instructed to contact the Food and Drug Administration (FDA) Center for Devices and Radiologic Health (CDRH) and obtain a written determination.

5.6. The IRB will notify the PI of the Board’s SR/NSR determination. If the IRB disagrees with the sponsor or PI’s determination that a device is NSR, the study can only be conducted within the Organization if an IDE is obtained. The PI is responsible for notifying the sponsor of the IRB’s determination. The PI must provide the IRB with confirmation of this action.

Note: In accordance with 21 CFR 812.150(b)(9), if the IRB determines that a device is SR and the sponsor had classified the device as NSR, the sponsor must submit to FDA a report of the IRB’s determination within 5 work days after the sponsor first learns of the IRB determination. If FDA does not agree with the IRB’s SR determination, the IRB will re-review the study. However, the IRB retains the ultimate authority in deciding whether or not to accept FDA’s NSR classification.

5.7. NSR device studies do not require submissionrequirements of an IDE application to the FDA before starting the study. The FDA considers an NSR device study to have an approved IDE application after obtaining and maintaining IRB approval. Sponsors and the PI must meet the abbreviated requirements at(per 21 CFR 812.2(b).c)); Thesespecifically: abbreviated requirements address labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion.

• 5.2.3.1.

  5.8.A If the IRB classifies amarketed device aswhen NSR,used theor IRB will continue to follow proceduresinvestigated in accordance with the IRB approval criteria HRPP policy 2.5 usedindications in consideringlabeling approval; of any research involving an FDA-regulated product including all applicable local and regulatory requirements.

  or

• 5.9. SR devices require submission of an IDE application to the FDA before starting the study. Final IRB approval and release of IDE studies is contingent upon the assigned IRB administrator’s receipt of FDA notification approving the IDE. All protocol-related documents, including FDA notification, must contain matching IDE numbers.

5.10. For studies involving marketed SR devices for potential new indications, the IRB may require submission of an IDE application to the FDA upon consultation with both the sponsor and the FDA.

5.11. All unanticipated adverse device effects (UADEs) will be reported in accordance with HRPP policy 8.1 (IRB Review of Adverse Events and Adverse Device Effects).

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6.0 Exemptions from IDE Requirements

6.1. Any of the following types of clinical investigations are exempt from IDE requirements (21 CFR 812.2(c)):

6.1.1. A clinical investigation with approved devices used in accordance with labeling. The device may have been approved for commercial distribution before May 28, 1976 or deemed substantially equivalent to a device commercially approved before May 28, 1976. 6.1.2.3.2. A clinical investigation with in vitro diagnostic devices,device, if the sponsortesting complies(i) withIs applicable labelling requirements in 21 CFR 809.10(c)noninvasive, and if(ii) the testing:

6.1.2.1. Is noninvasive; and 6.1.2.2. Doesdoes not require an invasive sampling procedure that presents significant risk;risk, and 6.1.2.3.(iii) Doesdoes not by design or intention introduce energy into a subject;subject, and 6.1.2.4.(iv) Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.procedure; or 6.1.5.2.3.3. A clinical investigation with a marketed device undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution, unlessif the testing is not for the purpose of determining safety or effectiveness and efficacydoes and/ornot putsput subjects at risk.risk; or 6.1.5.2.3.4. 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 as defined in § 812.3(b),device, unless the device is being used to determine safety or effectiveness for commercial distribution. 6.2.5.3. ExemptionThe fromdetermination IDEthat regulationsthe doesdevice is not meana significant risk device must be made by the studyconvened isIRB. exempt

from5.3.1. the IRB will review the sponsor’s determination of the risk classification of the device and approval.make Ifa determination of risk based at least upon the studyfollowing: involves

5.3.1.1. The potential harm associated with the device itself 5.3.1.2. The proposed use of athe device,device whether5.3.1.3. orAny notprocedure necessary for implantation of the device 5.3.1.4. A comparison of the risks of the device hasagainst beenthe approvedrisks byof 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, theor IRB’sother reviewdocumentation andor approvalcommunication ofverifying the studyIDE number .

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6.0 Investigator Responsibilities

6.1. The Investigator must comply with all applicableFDA localregulations and federaladditional regulations.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.

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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).

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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).

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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).

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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.