Expanded Access to Unapproved Devices
There are two options for treating patients with an unapproved medical device outside of a clinical trial.
One option is Expanded Access.
The other is Right to Try.
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)).
Investigational Device Exemption (IDE) - A Food and Drug Administration (FDA) approved IDE 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.
According to FDA regulations, an unapproved medical device may normally only be used on human subjects through an approved clinical study in which the subjects meet certain criteria and the device is only used in accordance with the approved protocol by a clinical investigator participating in the clinical trial.
However, FDA recognizes that there may be circumstances under which a health care provider may wish to use an unapproved device to save the life of a patient or to help a patient suffering from a serious disease or condition for which no other alternative therapy exists. Patients/physicians faced with these circumstances may request access to investigational devices under one of the following mechanisms by which FDA may make an unapproved device available.
Expanded Access: Emergency Use
List of Previous Emergency Uses of Test Articles (Drugs, Biologics and Devices) at UCI
As mentioned above, an unapproved device should normally only be used in human subjects if it is approved for clinical testing under an IDE and if it is used by an investigator for the sponsor in accordance with the terms and conditions of the application.
Emergency use of an unapproved device, however, may also occur when: (i) an IDE for the device does not exist, (ii) when a physician wants to use the device in a way not approved under the IDE, or (iii) when a physician is not an investigator under the IDE. The sponsor must notify the FDA within 5 days through submission of an IDE report describing the case and the patient protection measures that were followed.
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.
Criteria: The physician who intends to use the device must determine that the following criteria are met
- Life-threatening or serious disease or condition that needs immediate treatment
- No generally acceptable alternative treatment for the condition exists
- Because of the immediate need to use the device, there is no time to obtain FDA approval
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.
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.
Procedures for IRB Submission of Emergency Use
UCI IRB requires that, when possible, the IRB be notified in advance of the proposed emergency use of an unapproved device. The IRB notification is notified by completing the KRP Application for Emergency Use. There are two parts to this application. First, a new protocol application for emergency use must be completed prior to the emergency use of the unapproved device. The IRB Chair or Vice Chair will review and acknowledge the emergency use. Secondly, an amendment must be submitted for the same protocol to the IRB within five business days after the emergency use. Note that acknowledgment of the emergency use by the IRB Chair or Vice Chair should not be construed as IRB approval. IRBs are informed of Emergency Use situations during convened IRB meetings.
In the event of a waiver of informed consent for an emergency use, the IRB Chair or Vice Chair will confirm that both the investigator and a physician who is not otherwise participating in the clinical investigation 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 not sufficient to obtain consent from the patient’s legal 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;
If, in the investigator’s opinion, there is not sufficient time to obtain an independent physician’s determination that the four criteria are met, the investigator should make the determination and subsequently obtain (i.e., within five business days) a review of his/her determination by a physician not participating in the investigation.
NOTE: 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 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
Expanded Access Single Patient
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.
- 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 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 the expanded access use has ended.
Expanded Access Intermediate Size Populations
IRB Submission of Protocols for Expanded Access of Unapproved Devices
Expanded access protocols for devices must be submitted per usual IRB process. In the case of a single patient, a subcommittee review is possible. For intermediate size populations (i.e., more than one patient) full IRB review and approval is required under FDA regulations.
Other Treating Physician Responsibilities
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.
- FDA: Emergency Use Definition: 21 CFR 56.102(d)
- FDA: IRB Reporting: 21 CFR 56.104(c)
- FDA: Consent Exception: 21 CFR 50.23
- FDA: Physician Care: 21 CFR 50.25(e)
- FDA Information Sheet: Emergency Use of an Investigational Drug or Biologic
Resources for Expanded Access
- UCI Expanded Access Consent Template
- Definition of the 3 types of Expanded Access
- Individual Patient Expanded Access Applications: Form FDA 3926 (PDF - 356KB)
- Expanded Access for Medical Devices
- Federal Regulation on Expanded Access
- Timeline for registration and updating an Expanded Access Record
- Who should submit an Expanded Access record
- FDA "Project Facilitate"
- A new pilot program to assist oncology health care professionals in requesting access to unapproved therapies for patients with cancer
- "Project Facilitate" helps treating physicians submit an Expanded Access request for an individual patient