PURPOSE

The University of Utah Institutional Review Board (IRB) requires investigators to submit a plan that ensures the proper use and management of investigational or unlicensed test articles. Humanitarian Use Devices (HUD) must also be reviewed and approved by the University of Utah IRB.

SCOPE

This policy applies to clinical investigations conducted at the University of Utah.

DEFINITIONS

1. Clinical investigation is a term used in the Food and Drug Administration (FDA) regulations meaning any experiment that involves a test article (e.g., drug, device, or biologic) and one or more human subjects. It qualifies as a clinical investigation if it requires FDA approval before starting or the results are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit. The terms research, clinical research, clinical study, and study are used interchangeably with clinical investigation in this policy.
2. Test Article is a term used in the FDA regulations meaning drugs, biologics, and devices intended for human use. The FDA has authorization to regulate the development, approval, and marketing of these products.

POLICY

Clinical investigations will be reviewed and approved by the University of Utah IRB and must abide by FDA regulations.

Investigators, including sponsor-investigators, must abide by University of Utah Clinical Research Standard Operating Procedures regarding investigational new drug (IND) applications and investigational device exemption (IDE) applications. These policies are posted on the University of Utah Office of Quality Compliance (OQC) website.

Investigational drugs used at University of Utah Health (U Health), Primary Children’s Hospital (PCH) or VA Salt Lake City Healthcare System (VASLCHCS) must use the respective investigational pharmacies unless the pharmacy grants an exception. Documentation of a pharmacy exception must be included in the IRB submission. Investigators responsible for a drug study where drugs are stored and dispensed by an investigational pharmacy must abide by that pharmacy’s policies.

An approved Humanitarian Device Exemption (HDE) authorizes marketing of a Humanitarian Use Device (HUD).  A HUD is a device that is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or is manifested in fewer than 8,000 individuals in the United States per year. Before a HUD under an approved HDE can be used at the University of Utah or its affiliates for clinical care, approval by an IRB is required, with the exception of emergency use.

PROCEDURES

1. Review of Clinical Research Involving Investigational Drugs and Biologics
   1. Investigators must submit all information and documents required by the IRB for the use of investigational drugs and biologics in the new study application.
   2. If the research involves the use of a drug other than a marketed drug in the course of medical practice, the drug must either have an IND or the research must meet one of the FDA exemptions from the requirement to have an IND.
      1. If an IND number is required, the investigator will provide the IND number and verification of the IND number (i.e., FDA letter, IND number printed in the protocol, letter from the sponsor, or other sponsor-generated document). The investigator must also complete the investigational drug data form in the application.
      2. If the investigator believes an IND is not required, they may attach the FDA letter granting an IND exemption or they may confirm the study’s eligibility for exemption from the IND requirements.
   3. IRB reviewers complete reviewer checklists documenting that the IND number has been provided or that the IND exemption criteria are met and whether the plan to control the investigational drug is adequate. IRB reviewers may seek clarification from a representative of the appropriate investigational pharmacy. IRB reviewers may also contact a qualified person who is not an IRB member that is knowledgeable about the drug with any concerns that may affect the risk/benefit assessment.
   4. The IRB reviews the proposed research, informed consent document(s), the procedure for obtaining informed consent, and additional information, when applicable, to determine whether the study meets criteria for approval. IRB reviewers complete the reviewer checklist documenting how the criteria are met.
2. Clinical Research Involving Investigational Devices
   1. Investigators must submit all information and documents required by the IRB for the use of investigational device in the new study application.
   2. If the research involves the investigational use of a device, the investigator must indicate in the application whether the study is a non-significant risk (NSR) device study, a significant risk (SR) device study, or that the study is exempt from investigational device exemption (IDE) requirements. The investigator must also describe the plan to control the investigational device.
      1. If the investigator (or sponsor) claims the medical device is SR, the investigator must provide the IDE number and verification of the IDE number (i.e., FDA letter providing the IDE, IDE number printed in the protocol, letter from the sponsor, or other sponsor-generated document).
      2. If the investigator (or sponsor) claims the medical device is NSR, the investigator must provide a justification of why the medical device used in the study meets the definition of an NSR device.
      3. If the investigator (or sponsor) claims the medical device is exempt from IDE requirements, they must indicate the category of exemption from IDE requirements in the application.
   3.  The IRB reviews the proposed research, informed consent documents, the procedure for obtaining informed consent, and additional information, when applicable, to determine whether the study meets criteria for approval. IRB reviewers complete the reviewer checklist documenting how the criteria are met and if the plan to control the investigational device is adequate. IRB reviewers may seek clarification from other qualified representatives who are not IRB members that are knowledgeable about the control of investigational devices. IRB reviewers may also contact a qualified person who is not an IRB member that is knowledgeable about the device with any concerns that may affect the risk/benefit assessment.
   4. The IRB determines whether, in the context of the study or by the nature of the investigational medical device (see significant risk devices list and IDE requirements exemption criteria), the study presents a significant risk (SR) of harm to study subjects, a non-significant risk (NSR) of harm to study subjects, or if the study meets criteria for exemption from IDE requirements. This assessment is based on the information provided by the investigator and/or the sponsor. In deciding whether a medical device is a significant risk, the IRB considers if the device:
      1. Is intended as an implant and presents a potential for serious risk to health, safety, or welfare of a participant.
      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 participant.
      3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents the potential for serious risk to the health, safety, or welfare of a participant.
      4. Otherwise presents a potential for serious risk, safety, or welfare of a participant.
   5.  IRB reviewers complete the board reviewer checklist (Risk Determination for Devices portion) documenting the risk determination. If the convened IRB disagrees with the determination made in the checklist, the minutes will reflect the discussion, resolution and final risk determination.
      1. Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling may be reviewed using expedited review procedure.
      2. If the convened IRB agrees with a NSR determination, the study may begin after IRB notification and FDA does not need to be notified.
      3. If the IRB determines that an investigation, presented for approval as a non-significant risk device study involves a significant risk device, the IRB administrator notifies the investigator and, where appropriate, the sponsor. The IRB will not approve the study until the FDA issues a device determination of significant risk or non-significant risk and all associated requirements are met.
3. IRB Oversight of a Humanitarian Use Device
   1. The convened IRB must review an initial application for the use of a HUD. Continuing review of a HUD may be done by way of an expedited procedure (similar to the expedited procedure described in section 21 CFR 56.110(b)) unless the IRB determines that a convened board must conduct continuing review.
   2. The IRB does not require a review and approval process for each individual use of a HUD. The IRB may approve the use of the HUD without any further restrictions, use of the device under a protocol, or use of the device on a case-by-case basis.
   3. The IRB requires that informed consent and documentation of consent be obtained when treating or diagnosing a patient with the use of a HUD. The convened board will consider exceptions to the requirement of full informed consent and documentation of consent on a case-by-case basis.