Introduction

The Food and Drug Administration’s (FDA) Expanded Access Program offers a potential pathway for patients with serious or immediately life-threatening diseases or conditions to gain access to an investigational medical product (a treatment not yet approved by the FDA) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

Before using an investigational medical product (drug, biologic, or medical device), patients and their physicians must carefully consider the risks. These products haven’t been proven safe or effective by the FDA and may or may not help treat the condition. They could also cause serious, unexpected side effects.

Whenever possible, these products should be used in a clinical trial, which offers more oversight and data collection. Expanded access, sometimes called “compassionate use”, may provide a way to use the investigational product if joining a clinical trial isn’t possible.

This guidance focuses on the IRB review of expanded access to investigational drugs and devices. Physicians must rely on FDA regulations and guidance for all FDA requirements including how to submit expanded access requests, and reporting requirements.

Guidance on emergency use is not included here but can be found in IRB Guidance Emergency Use of a Test Article.

Definitions

Immediately life-threatening disease or condition: Immediately life-threatening disease or condition means a stage of disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment. (21 CFR 312.300)

Investigational medical product: Includes investigational new drugs and biologics, and investigational devices. Investigational new drug means a new drug or biological drug that is used in a clinical investigation. The terms “investigational drug” and “investigational new drug” are deemed to be synonymous. Investigational device means a device, including a transitional device, that is the object of an investigation. (21 CFR 312.3 and 21 CFR 812.3).

Guidance

The FDA has published Information the following helpful expanded access guidance:

• Information for Patients
• Information for Physicians

Investigational Drugs

An investigational new drug number (IND) is required for expanded access. An individual physician may apply to the FDA for an IND or may function under an existing IND held by another physician or the drug manufacturer. Some IND holders will not allow expanded access to be amended to their existing IND; in this case, the physician must apply for a new IND. Physicians must communicate with the IND holder to determine if an existing IND can be amended.

The University of Utah IRB is responsible for initial and continuing review of expanded access protocols to ensure the informed consent requirements of 21 CFR 50 are met. The University of Utah IRB has an expanded access application in ERICA (Application for Expanded Access of an Investigational Drug or Device). IRB applications for expanded access will generally be reviewed by the convened IRB (including intermediate and treatment INDs and protocols), except in cases of emergency use or when a physician requests a waiver of full IRB review for individual patient expanded access, as described below.

Individual Patient Expanded Access INDs

For individual patient expanded access INDs, physicians may request a waiver of the full IRB review requirement under 21 CFR 56.105. In such cases, an IRB chair or designated IRB member may agree to the treatment before it begins.

• The IRB chair or designee will review the application and required documentation. Physicians must submit the signed Form FDA 3926 with box 10.b checked. The FDA will not send a separate notice confirming the waiver. The physician must indicate in the IRB application that they are requesting a waiver of the full IRB review requirement.
• Alternatively, physicians may submit a separate waiver request as part of an IND amendment. If they choose this route, the FDA will respond directly to the waiver request. The physician must provide the IRB with verification from the FDA that the amended IND is approved.

Both options described above are available in the Application for Expanded Access of an Investigational Drug or Device. If a waiver of the full IRB review requirement is not requested, the application will be reviewed by the convened IRB.

Investigational Devices

The FDA’s Expanded Access Program allows patients with serious or life-threatening conditions to access investigational medical devices (i.e., not FDA-approved) outside of clinical trials, when no comparable or satisfactory alternatives are available. Expanded access requires FDA submission and IRB review. Informed consent must be obtained according to FDA regulations.

Compassionate Use is for individual patients or small groups with serious conditions and no available alternatives. Compassionate use requires FDA approval with the concurrence of the University of Utah IRB Chair.

Treatment Use is for broader use in patients with serious or life-threatening when the device is also being studied under an approved Investigational Device Exemption (IDE). Treatment use is reviewed by the convened IRB.

The University of Utah has a specific application for expanded access (Application for Expanded Access of an Investigational Drug or Device) in ERICA.

Documents and References

FDA Guidance: Expanded Access

FDA Guidance: Expanded Access Information for Institutional Review Boards (IRBs)

FDA Guidance: Expanded Access Keywords, Definitions, and Resources

FDA Guidance: Expanded Access to Investigational Devices

FDA Guidance: Expanded Access Categories for Drugs (Including Biologics)

IRB SOP 507: Expanded Access

21 CFR 312 Subpart I – Expanded Access to Investigational Drugs for Treatment Use

University of Utah Expanded Access Consent Checklist

University of Utah IRB Guidance – Emergency Use of a Test Article

Points to Consider