Emergency, Expanded Access for an Investigational Medical Product (One Patient)
Version Date: March 2020
Under FDA regulations, an investigational medical product may be used to treat a patient with an immediately life-threatening condition or serious disease or condition outside a clinical trial when no comparable or satisfactory alternative therapy options are available. The is called expanded access or compassionate use. This document addresses only emergency uses of an investigational medical product in one patient under the expanded access regulations. If you have any questions about this guidance or a potential emergency use, please contact emergencyuse@hsirb.wisc.edu.
For expanded access for a single patient or group of patients in a non-emergency setting (I.e. there is time to obtain prospective IRB approval), see Expanded Access of Investigational Medical Product Requests (Non-emergency).
What Is Expanded Access
FDA guidance states that using an investigational medical product under expanded access regulations (including emergency uses) may be appropriate when all the following apply:
- Patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition.
- There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
- Patient enrollment in a clinical trial is not possible.
- Potential patient benefit justifies the potential risks of treatment.
- Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.
The treating clinician should confirm that all the above criteria have been met before proceeding with an emergency use request.
Criteria for Emergency Use
To qualify as an emergency under FDA regulations, the proposed use must meet the following criteria, which differ for drugs/biologics and devices.
For a drug or biologic:
- Patient is in a life-threatening or severely debilitating situation;
- No standard acceptable treatment is available; AND
- There is insufficient time to obtain IRB approval prior to the proposed date of use.
For a device:
- Patient has a life-threatening condition that needs immediate treatment;
- No generally acceptable alternative treatment for the condition exists; AND
- There is insufficient time to obtain IRB approval prior to the proposed date of use.
- Because of the immediate need to use the device, there is not time to use existing procedures to obtain FDA approval for the use.
The FDA defines life-threatening as 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 subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
The FDA defines severely debilitating as 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.
Contacting the Manufacturer
For all types of investigational medical products, the FDA requires that the clinician contact the manufacturer to see if they will provide the investigational medical product for expanded access use. The manufacturer may provide the investigational medical product for use under its own IND or IDE.
If no IND for use of a drug or biologic exists, the clinician may need to obtain their own IND; however, the FDA may authorize shipment of a drug or biologic in advance of an IND submission in an emergency. For devices, the FDA does not require the clinician to obtain an IDE in emergency use situations if one does not already exist. See “Reporting to the FDA” below for contact information for the FDA.
Contacting the Pharmaceutical Research Center (PRC)
For emergency use of a drug or biologic only, the clinician must contact the PRC for assistance (608.263.8902).
Initial Notification to the FDA
- For drugs or biologics, clinicians MUST contact the FDA prior to use of the drug or biologic. Step-by-step instructions for this process are here: https://www.fda.gov/news-events/expanded-access/expanded-access-how-submit-request-forms#AccessPhysEmerg.
- For devices, clinicians are NOT required to contact the FDA prior to use of the device IF all the criteria listed above under “Criteria for Emergency Use” are met. The FDA still advises that the clinician follow as many patient protection measures as possible when emergency use of a device occurs. These include obtaining:
- Informed consent from the patient or a legal representative;
- Clearance from the institution as specified by their policies;
- Concurrence of the Institutional Review Board (IRB) chairperson;
- An independent assessment from an uninvolved physician; and
- Authorization from the device manufacturer.
To contact the FDA for approval of or guidance regarding a potential emergency use, please see the contact information found at the bottom of this page: https://www.fda.gov/news-events/public-health-focus/expanded-access.
Initial Notification to the IRB
For use of investigational medical products, clinicians should notify the IRB of the proposed use prior to the actual use or, if not feasible, within five days of the use. Please notify the IRB as follows:
- During business hours (Monday-Friday, 8AM-5PM), notify the IRB of the proposed emergency use by email (irbdirector@hsirb.wisc.edu and csrogers@wisc.edu) and include the following information:
- Description of how the use meets the criteria outlined above in the “Criteria for Emergency Use”, including whether any other reasonable alternative treatments are available;
- Summary of the patient’s diagnosis and treatment history; and
- Date and/or timing of the proposed use;
- Description of the informed consent process, including when and from whom consent will be obtained; and
- Attach the following as appropriate:
- Draft consent document
- For drugs or biologics only, documentation of approval of the use from the FDA (or include in the email the date when the request was submitted to the FDA).
- For devices only, a concurrence letter from an independent physician that states that use of device is warranted and no other reasonable alternative treatments are/were available.
- See “IRB Chair Concurrence Process” below for next steps in the process.
- Outside business hours, clinical judgement prevails over the need for administrative procedures. Emergency use of an investigational medical product in one patient outside IRB business hours may proceed as follows:
- For a drug or biologic, notify the PRC.
- Notify the IRB of the use by voicemail (608.263.2362) and email (emergencyuse@hsirb.wisc.edu).
- Within 5 business days of the use, submit a treatment use application in ARROW (see “Reporting to the IRB”, below).
- The application will then be reviewed by the convened IRB to determine a) whether the use met the criteria for emergency use of an investigational medical product per the FDA and b) that informed consent was obtained or met the criteria for exception to the requirements for informed consent (see “Obtaining Informed Consent” section below).
IRB Chair Concurrence Process
- If the IRB chair concurs with the request and agree it meets applicable IRB requirements, the treating physician will receive an acknowledgement via email.
- If the IRB chair determines that sufficient time exists for the convened IRB to review the request, the treating physician will need to submit an expanded access application in ARROW and treatment will be allowed to begin following IRB approval of the application.
Obtaining Informed Consent
For all emergency uses, informed consent must be obtained from the patient or their legally authorized representative prior to treatment unless the criteria in 21 CFR 50.23(a) are met.
Reporting to the IRB
If not completed before use, a treatment use application must be submitted in ARROW within 5 days of the emergency use. This application will be reviewed by the convened IRB to determine whether the convened board agreed with the IRB Chair’s assessment or additional information should be provided to the patient (or their representatives).
Reporting to the FDA
Additional reporting to the FDA may be required following the emergency use of the test. Please contact the FDA for guidance on what additional reporting may be required.
Resources
- For assistance in preparing an expanded access application, please contact the Office of Clinical Trials (OCT).
- Additional information for physicians about expanded access can be found on the FDA’s website.