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6.1 Research Involving Investigational and Marketed Drugs

Last Revised: 1/24/2024

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

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for research involving investigational or marketed drugs and biologics 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 the use of drugs and biologics in accordance with 21 CFR 50, 56; 21 CFR 312, 314; and 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 312.50 through 59

3.0 Definitions

  • 3.1. Investigational Drug: a) an unapproved drug or a biologic that is used in a clinical investigation, or b) a marketed drug that is the object of a clinical investigation.

  • 3.2. Clinical Investigation: any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice (21 CFR 312.3(b)).

  • 3.3. Investigator: an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the drug is administered or dispensed to a subject). In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team (21 CFR 3123(b)).

    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).

  • 3.4. Subject: means an individual who participates in an investigation, either as a recipient of the investigational drug or as a control. A subject may be a healthy human or a patient with a disease (21 CFR 312.3(b)).

  • 3.5. Investigational New Drug (IND) Application: an application submitted to FDA to conduct a clinical investigation with an investigational drug that is subject to 21 CFR 312.2(a).

  • 3.6. Marketed Drug: a drug or biologic approved by FDA for marketing and is generally in use for treatment purposes.

  • 3.7. Sponsor: a person or organization who takes responsibility for and initiates a clinical investigation. The sponsor may be a pharmaceutical company, governmental agency, academic institution, private organization or an individual investigator. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator (21 CFR 312.3(b)).

  • 3.8. Sponsor-Investigator: an individual that both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. An investigator who also serves as a sponsor must comply with all FDA requirements applicable to both an investigator as well as a sponsor (21 CFR 312.3(b)).

  • 3.9. Emergency Use: the 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.

  • 3.10. Expanded Access: the use of an investigational agent outside of a clinical trial. “Expanded access” is also referred to as “compassionate use” though this term is not defined or described in FDA regulations.

4.0. Organizational Responsibilities

  • 4.1. All contracts involving sponsored research conducted at UNMC/NM or CN (or affiliated clinics) where the investigational or marketed drugs 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 drugs that are the objects of the investigation, the IRB will (1) ensure that a valid IND is in effect for any drug study subject to 21 CFR 312.2(a) OR (2) ensure that an IND is not required.
    • 5.2.1. A clinical investigation of a marketed drug is exempt from the requirements of an IND (per 21 CFR 312.2(b)(1)) if:
      • 5.2.1.1. The investigation is not intended to be reported to FDA in support of a new indication for use or any other significant change in the labeling for the drug; AND
      • 5.2.1.2. The investigation is not intended to support a significant change in the advertising for the product; AND
      • 5.2.1.3. The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug; AND
      • 5.2.1.4. The investigation is conducted in compliance with 21 CFR 50, 56, and 21 CFR 312.7 (Promotion of investigational drugs)
    • 5.2.2. A clinical investigation involving blood grouping serum, reagent red blood cell and anti- human globulin is exempt from the requirements of an IND if (a) it is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure, and (b) it is shipped in compliance with 312.160 (per 21 CFR 312.2(b)(2)).
    • 5.2.3. A drug intended solely for tests in vitro or in laboratory research animals is exempt from the requirements of an IND if it is shipped in accordance with 21 CFR 312.160 (per 21 CFR 312.2(b) (3))
    • 5.2.4. A clinical investigation involving use of a placebo is exempt from the requirements of an IND if the investigation does not otherwise require submission of an IND (21 CFR 312.2(b)(5)).
  • 5.3. Documentation of the IND could be the industry sponsored protocol with the IND number, written determination from the FDA, or other documentation or communication verifying the IND 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 312. 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 that investigational drugs are securely stored and dispensed in accordance with FDA regulations at 21 CFR 312.60 through 62.
  • 6.3. If a study involves an investigator-initiated IND, the PI will comply with additional sponsor requirements per 21 CFR 312.50, and certify compliance by submitting Addendum O (Principal Investigator Responsibilities: Investigator-Initiated Drug 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 Drugs

Expanded Access to Investigational Drugs 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 Drugs

Emergency use of an investigational drug 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: 1/25/2016 (Approved: 1/25/2016) - original author not recorded

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

 Revised: 1/24/2024 - add reference to FDA 30-day rule (section 5.1.1); added IND exemption 4 (section 6.4).

 Revised 3/17/2026 – extensive stylistic revisions; removed information present in other policies; deleted requirement that clinical investigations involving drugs must be reviewed by the convened IRB.

 Revised 6/10/2026 - clarified definitions of investigational drug and clinical investigation to match regulatory definitions; further stylistic revisions to describe organization’s, IRB/ORA’s and investigator’s responsibilities; 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 drugs are securely stored and dispensed in accordance with FDA regulations; removed materials redundant to other policies (Expanded Access); other stylistic changes.

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