Expanded Access to Unapproved Medical Devices

NOTE: An emergency use DOES NOT require IRB Concurrence or FDA approval BEFORE use.

Unapproved medical device: is a device that is utilized for a purpose, condition, or use for which the device requires, but does not have, an approved application for premarket approval under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360e)(the act) or an approved IDE under section 520(g) of the act (21 U.S.C. 360j(g)).

IDE: An approved investigational device exemption permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device.

If enrollment in an existing clinical trial is not possible (e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials to address the patient’s condition), patients/physicians have the potential to receive expanded access to investigational devices under one of three alternative mechanisms.

Single Patient Emergency Use of an Unapproved Medical Device:

Note:  DO NOT USE CRConnect or Protocol Builder to create your templates.

The FDA defines "emergency use" as the use of a test article when:

1. The patient has a life-threatening condition that needs IMMEDIATE treatment.
2. No generally acceptable alternative treatment for the condition exists; and
3. Because of the immediate need to use the medical device, there is no time to use existing procedures to obtain FDA approval for the use obtain IRB approval [21 CFR 56or.102 (d)] [PDF].

Emergency use of an unapproved device may also occur when:

1. An IDE for the device does not exist, or
2. When a physician wants to use the device in a way not approved under the IDE, or
3. When a physician is not an investigator under the IDE 

Life-threatening, for the purposes of section 56.102(d), includes the scope of both life-threatening and severely debilitating, as defined below.

• Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the patients must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
• Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

FDA expects the physician to make the determination that the patient’s circumstances meet the above criteria (1-3), to assess the potential for benefit from the use of the unapproved medical device and to have substantial reason to believe that benefits will exist.

If there is an IDE for the unapproved medical 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 UVA physician should submit a follow-up report on the use of the device (description of device used, details of the case, and the patient protection measures that were followed) 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

Procedures for IRB submission for Single Patient Emergency Use of an Unapproved Medical Device

Emergency Use does not need IRB concurrence or FDA approval before use. However, if there is time, the UVA IRB-HSR asks that, the IRB-HSR be notified in advance of the proposed emergency use of an unapproved medical device.  

FDA guidance indicates that BEFORE using an unapproved medical device, the physician should take as many of the following patient protection measures as possible, and provide the following information in the submission:

• Obtain a written independent assessment of the use of the device by an uninvolved, independent physician.
• Obtain documented informed consent from the patient or patient’s legally authorized using the template: Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device
  • If consent cannot be obtained before use, please let the IRB-HSR know why this was the case in your correspondence. The UVA physician and an independent licensed physician who is not participating in the medical care of the patient must certify in writing that:
    • • The patient has a life-threatening or serious disease or condition
      • There was an inability to communicate with or obtain legally effective informed consent from the patient
      • There was not sufficient time to obtain informed consent from the subject or legally authorized representative
      • There was no available alternative method of FDA-approved or generally recognized therapy that provided an equal or greater likelihood of saving the patient’s life.
• Obtain documented authorization from the holder of the IDE/device manufacturer.
• Obtain clearance from UVA Clinical Engineering for use of the unapproved investigational medical device.
• Notify the UVA IRB using the form “Expanded Access - Single Patient Emergency Use of Investigational Device" along with the completed informed consent template, and the IDE holder’s authorization.

NOTE: In the event of a waiver of informed consent for an emergency use, the IRB Chair or Designated IRB member, will confirm that both the investigator and an independent physician who is not otherwise participating in the care of the patient, have certified in writing all of the following:

• the patient is confronted by a life-threatening situation necessitating use of the test article;
• informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the patient;
• time is insufficient to obtain consent from the patient’s legally authorized representative;
• no alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the patient’s life;

Prior FDA approval for shipment or use of the device is not necessary but emergency use needs to be reported to the FDA and IRB. The information to the FDA should be submitted by the sponsor (IDE holder). If the unapproved medical device is not under an IDE, the investigator should submit the information directly to the FDA.

Send the following documentation to the UVA IRB via IRBHSR@virginia.edu

Subject: Request for Single Patient Treatment Use of an Unapproved Medical Device 

Emergency use must be reported within five working days to the UVA IRB-HSR and the FDA.

Include the following documentation:

• Expanded Access - Single Patient Emergency Use of Investigational Device
• Copy of the IDE protocol or treatment plan with description of device and name of IDE holder, if this exists.
• A copy of the informed consent that was used. You may use the template: Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device.  If a consent form was not used, please let us know why consent was not obtained (as explained above). For example, if there was not time to consent the subject, please explain how the subject (or legally authorized representative) was informed after the use. You may submit an unsigned copy of the informed consent, so you can obtain documentation of consent after the IRB reviews the use.
• Copy of Authorization from the IDE holder
• Obtain clearance from Clinical Engineering for use of the unapproved investigational medical device (New Medical Device Application)
• IDE# and FDA Acknowledgment (this can be obtained before or after the IRB Concurrence)

Single Patient Non-Emergency Use of an Unapproved Medical Device

Note:  DO NOT USE CRConnect or Protocol Builder to create your templates.

FDA approval and IRB Concurrence is required BEFORE the use of the unapproved medical device in a non-emergent situation for a single patient. The submissions to the FDA and the IRB -HSR can occur simultaneously, but both are needed before use.

FDA guidance indicates that BEFORE using an unapproved medical device, the physician should take as many of the following patient protection measures as possible, and provide the following information in the submission:

• Obtain a written independent assessment of the use of the device by an uninvolved, independent physician.
• Obtain documented informed consent from the patient or patient’s legally authorized using the template:  Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device
  • If consent cannot be obtained before use, please let the IRB-HSR know why this was the case in your correspondence. The UVA physician and an independent licensed physician who is not participating in the medical care of the patient must certify in writing that:
    • • The patient has a life-threatening or serious disease or condition
      • There was an inability to communicate with or obtain legally effective informed consent from the patient
      • There was not sufficient time to obtain informed consent from the subject or legally authorized representative
      • There was no available alternative method of FDA-approved or generally recognized therapy that provided an equal or greater likelihood of saving the patient’s life.
• Obtain documented authorization from the holder of the IDE/device manufacturer
• Obtain clearance from Clinical Engineering for use of the unapproved investigational medical device

Notify the UVA IRB with a written description of the circumstances necessitating the use of the device, along with documentation of the uninvolved physician’s assessment, informed consent, and the IDE holder’s authorization.

The physician who intends to use the device must determine that the following criteria are met:

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

Single Patient Non-Emergency Treatment Use of an Investigational Medical Device

Send the following documentation to the UVA IRB-HSR via IRBHSR@virginia.edu Subject: Request for Single Patient Non-Emergency Treatment Use of an Unapproved Medical Device 

• Request for IRB Concurrence for Single Patient Non-Emergency Treatment with an Investigational Drug/Biologic and Device
• Copy of an uninvolved physician’s assessment of use.
• Copy of the IDE protocol or treatment plan with description of device and name of IDE holder, if this exists.
• A copy of the informed consent that was used. You may use the template: Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device.  If a consent form was not used, please let us know why consent was not obtained (as explained above). For example, if there was not time to consent the subject, please explain how the subject (or legally authorized representative) was informed after the use. You may submit an unsigned copy of the informed consent, so you can obtain documentation of consent after the IRB reviews the use.
• Copy of Authorization from the IDE holder
• Obtain clearance from Clinical Engineering for use of the unapproved investigational medical device
• IDE# and FDA Acknowledgment

The sponsor of the IDE/device manufacturer 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 physician may not treat the patient identified in the IDE supplement until FDA approves the treatment use for the intended patient.  FDA will consider preliminary evidence of safety and effectiveness as well as whether the compassionate use would interview 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 compassionate use has ended.

FOLLOW-UP:

After the use of the test article, you are required to notify the UVA IRB-HSR within 5 working days about the status of the patient using the Single Patient Treatment Follow-up form.  The FDA and sponsor will need a similar report. Be aware of the reporting requirements noted in the table that follows.

Treatment Use for Unapproved Medical Devices  (intermediate or large groups)

These procedures are intended to facilitate that availability of devices that are not FDA approved for marketing but are under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom there is no comparable or satisfactory alternative device or treatment available.  During the trial or prior to final FDA action on the marketing approval, it may be appropriate to use the device to treat patients not in the trial under treatment IDE regulations (21 CFR 812.36).
For the purposes of treatment use, immediately life-threatening disease means a stage of a 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.

The physician who intends to use the device must determine that the following criteria are met:

• The device is intended to treat or diagnose a serious or immediately life-threatening disease or condition;
• There is no comparable or satisfactory alternative device or other therapy available to treat or diagnose that stage of the disease or condition in the intended patient population;
• The device is under investigation in a controlled clinical trial for the same use under an approved IDE, or such clinical trials have been completed; and
• The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence.

Procedures for IRB submission of protocols for treatment use of unapproved devices

For investigator-initiated IDEs, compassionate use protocols must be submitted per usual procedures through CRConnect and the UVA IRB-HSR and requires full IRB review and approval under FDA regulations.  Please see the School of Medicine website for information about preparing an IDE submission to FDA.

Continued Access (Extended Investigation) of an Unapproved Medical Device

FDA may allow continued enrollment of subjects after the clinical trial under an IDE has been completed to allow access to the investigational medical device while the marketing application is being prepared by the sponsor or reviewed by FDA.  This is known as an “extended investigation”. A sponsor’s request for an extended investigation should be submitted as an IDE supplement. 

The physician who intends to use the device must determine that the following criteria are met:

• Public health need for the device, OR
• Preliminary evidence that the device will be effective and there are no significant safety concerns

Procedures for IRB submission of protocols for continued access to unapproved devices

For investigator-initiated IDE supplements for an extended investigation, continued access protocols must be submitted per usual procedures through CRConnect and the UVA IRB-HSR and requires full IRB review and approval under FDA regulations.  Please see the School of Medicine website for information about preparing an IDE submission to FDA.