Expanded Access to Unapproved Devices

Emergency use is when there is a need to use a device that has not received the FDA’s approval or clearance in an emergency. Expanded access to an investigational device under the emergency use mechanism is intended to provide patients and physicians with access to investigational devices to address immediately life-threatening situations when there is no available alternative and no time to use existing procedures to obtain FDA approval.

Emergency use may apply if the device is being studied in clinical trials under an investigational device exemption (IDE) such as when a physician who is not part of the IDE clinical study wishes to use the device to treat a patient in an immediately life-threatening situation. An IDE allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data.  Emergency use may also apply if there is no IDE or ongoing clinical studies for the device.

Criteria for Emergency Use

• The patient has a life-threatening condition that needs immediate treatment;
• No generally acceptable alternative treatment for the condition exists; and
• Because of the immediate need to use the device, there is no time to use existing procedures to obtain FDA approval for the use.

Is FDA approval required prior to Emergency Use?

No. If all of the above criteria are met, an unapproved device may be used in an emergency situation without prior approval by the FDA.

The FDA expects the physician to make the determination that the patient's circumstances meet the above criteria, to assess the potential for benefit from the use of the unapproved device, and to have substantial reason to believe that benefits will exist. In the event that a device is used in circumstances meeting the criteria listed above, the physician should follow as many patient protection procedures as possible. Such patient protection procedures include obtaining:

1. Informed consent from the patient or a legal representative;
2. Clearance from the institution as specified by their policies;
3. Concurrence of the Institutional Review Board (IRB) chairperson;
4. An independent assessment from an uninvolved physician; and
5. Authorization from the device manufacturer.

Under the emergency use provisions in the FDA regulations (21 CFR 56.104(c)), the emergency use of an unapproved test article is an exemption from prior review and approval by the IRB, but must be reported to the IRB within 5 working days. FDA guidance indicates that the physician should follow as many patient protection procedures as possible, including:

• Informed consent from the patient or a legal representative
• Clearance from the institution as specified by their policies
• Concurrence of the IRB Chairperson
• An independent assessment from an uninvolved physician; and
• Authorization from the IDE sponsor, if an approved IDE exists.

IRB Submission: Step by Step Instructions:

1. At any stage in the following process, for assistance in determining whether an emergency use of a test article in a life threatening situation meets the criteria for use, contact the UCI Human Research Protection staff at one of the following numbers (during business hours (M-F, 8-5)): IRB A Administrator India: 949-824-1082 or IRB B Administrator Cheree: 949-824-3711.  Physicians may also reach out to the IRB Chairs.  IRB A Chair: Tahseen Mozaffar, MD.  IRB B Chair: Kenneth Linden, MD, PhD.
2. Optional Initial Submission to the IRB: The PI may submit an application in ZOT IRB via the Reportable New Information module. This is not required however note that the FDA does suggest that concurrent from an IRB Chairperson should be obtained.  This may be achieved through a prospective ZOT IRB Application. Complete the following:
   1. The PI Worksheet for Emergency Use: HRP-322 PI WORKSHEET - Emergency Use
   2. An Expanded Access Consent form (this will be used to consent the patient regardless if IRB review occurs prospectively): HRP-506 CONSENT - Expanded Access
   3. If consent cannot be obtained provide the physician attestation. This is included as part of the PI Worksheet for Emergency Use: HRP-322 PI WORKSHEET - Emergency Use
   4. Sponsor Letter of Authorization for the use of the IDE (if applicable) and
   5. FDA Authorization (if available - not required prior to use)
   6. An independent assessment from an uninvolved physician of the proposed use
3. Upon receipt of the IRB application of Emergency Use for the single patient, HRP Staff will notify the IRB (i.e., the IRB Chair or a designee not involved in the patient's care). The IRB will review the documentation to determine whether the circumstances will follow regulatory or legal requirements for use of a test article.
4. Required IRB Submission: Within five working days of the emergency use, the investigator must provide the IRB with follow-up information and documentation regarding the emergency use. The PI must submit an application in ZOT IRB via the Reportable New Information module.This is a federal requirement. No exceptions.
5. If an initial IRB submission was not made,  at the time of the five working day follow up, provide all documents as noted in 4.1, 4.2, 4.3, 4.4, 4.5 and 4.6 above.  If an initial IRB submission was made, provide any requisite materials not already submitted.
6. The IRB will review the Emergency use of the test article and the follow up report at a Committee to determine whether the circumstances follow regulatory requirements for the emergency use of a test article, consent was obtained in accordance with FDA regulations, or the circumstances met the exception to the requirement for consent.
7. The investigator should maintain copies of all paperwork involved in the emergency use.
8. Physicians should consult with the Clinical Trials Team in Sponsored Projects Administration to determine whether an agreement is necessary with the sponsor/manufacturer.
9. In addition, physicians must consult with UCI Health Research Revenue Integrity (RRI) to determine any related billing implications, as well as confirm the registration of the patient in OnCore.
10. There will be additional paperwork and report filing as required by sponsors, drug companies, and the FDA (such as follow up/ annual reporting requirements). This is the responsibility of the UCI Principal Investigator. FDA follow up requirements are listed below.

Reporting the Emergency Use to the FDA

If there is an IDE for the device, the IDE sponsor must notify the FDA of the emergency use within 5 days through submission of an IDE Report (§812.35(a)(2)). This follow-up report should include a summary of the conditions constituting the emergency, the patient protection measures that were followed, and patient outcome information.

If no IDE exists, the physician should submit to the FDA a follow-up report within 5 days on the use of the device including: a description of device used, details of the case, and the patient protection measures that were followed.  The report should be submitted to:

Food and Drug Administration
Center for Devices and Radiological Health
10903 New Hampshire Ave
Document Control Center
WO66 Rm G-609
Silver Spring, MD 20993

Reference

The FDA allows for access to an investigational device for patients who are not eligible for the clinical trial but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. Expanded access may be used only during the clinical trial for which the device is being tested. Expanded access may be approved for a single patient or a small group of patients.

Criteria:

• The device is intended to treat or diagnose a serious disease or condition
• There is no comparable or satisfactory alternative device or therapy available

Prior Institional Review Board (IRB) and FDA approval is required before expanded access use may occur / the patient may be treated. The sponsor of the IDE is required to submit an IDE supplement requesting approval under 812.35(a) in order to treat the patient. For further instructions about FDA requirements for the IDE supplement, please refer to the FDA website.

FDA will consider preliminary evidence of safety and effectiveness as well as whether the expanded access would intervene with the conduct of a clinical trial to support marketing approval. Once approved, the patient should be monitored for safety. Follow up information on the use of the device should be submitted in an IDE Report after the expanded access use has ended.

The FDA provides guidance on How to Request Single Patient Expanded Access.

IRB Submission Process:

• Researchers should submit a new study application in ZOT IRB.
• Complete PI WORKSHEET - Expanded Access
• Also include a completed HRP-506 CONSENT - Expanded Access
• To streamline the submission process for individual patient compassionate use, FDA guidance allows for review and approval  by an IRB chair or by a designated IRB member, before the treatment use begins.
• Physicians should consult with the Clinical Trials Team in Sponsored Projects Administration to determine whether an agreement is necessary with the sponsor/manufacturer.
• In addition, physicians must consult with UCI Health Research Revenue Integrity (RRI) to determine any related billing implications, as well as confirm the registration of the patient in OnCore.

The FDA allows for access to an investigational device for patients who are not eligible for the clinical trial but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. Expanded access may be used only during the clinical trial for which the device is being tested. Expanded access may be approved for a single patient or a small group of patients. Expanded access to intermediate size populations provides access to an investigational device for use by more than one patient, but generally fewer patients than are treated under a typical treatment protocol.

Criteria:

• The device is intended to treat or diagnose a serious disease or condition
• There is no comparable or satisfactory alternative device or therapy available

This type of expanded access is used when multiple patients with the same disease or condition seek access to a specific drug or biological product that has not been approved by the FDA.

Prior Institional Review Board (IRB) and FDA approval is required before expanded access use may occur / the patient may be treated. The sponsor of the IDE is required to submit an IDE supplement requesting approval under 812.35(a) in order to treat the patient. For further instructions about FDA requirements for the IDE supplement, please refer to the FDA website.

The FDA allows for access to an investigational device for patients who are not eligible for the clinical trial but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. Expanded access may be used only during the clinical trial for which the device is being tested. Expanded access may be approved for a single patient or a small group of patients. Expanded access to intermediate size populations provides access to an investigational device for use by more than one patient, but generally fewer patients than are treated under a typical treatment protocol.

Criteria:

• The device is intended to treat or diagnose a serious disease or condition
• There is no comparable or satisfactory alternative device or therapy available

Allows a large, widespread population access to a drug or biological product that has not been approved by the FDA. This type of expanded access can only be provided if the product is already being developed for marketing for the same use as the expanded access use.

Prior Institional Review Board (IRB) and FDA approval is required before expanded access use may occur / the patient may be treated. The sponsor of the IDE is required to submit an IDE supplement requesting approval under 812.35(a) in order to treat the patient. For further instructions about FDA requirements for the IDE supplement, please refer to the FDA website.