Expanded Use of Investigational Drugs and Devices

The regulations allow clinicians to use an unapproved drug, biologic or device without prior IRB approval in limited circumstances; however, the clinician must comply with FDA requirements in these situations. 

When seeking to use an unapproved product, it is critical that the patient and his/her licensed physician consider all possible risks because the FDA has not determined whether the products are safe. Such products may, or may not, be effective in the treatment of the condition.

 

 Compassionate Use Workflow

  • Emergency Use

    “Emergency Use” is a provision of the FDA regulations that allows a physician to use an investigational product in a life-threatening emergency when there isn’t sufficient time to obtain IRB review and approval.  Physicians must complete the following seven steps.

    Step One

    When you decide that the investigational product is the best option for the patient in an emergency, contact the FDA to obtain approval. 

    1. For an investigational drug or biologic call (888) 463-6332 or email druginfor@fda.hhs.gov
    2. For an investigational device call (301) 796-7100 or email dice@fda.hhs.gov.

     

    Step Two

    The next step is to contact the sponsor and obtain agreement for the use of the investigational product.  

     

    Step Three

    Check to see if the regulatory criteria for use of the investigational product without IRB approval are met by reviewing  Worksheet Emergency Use (HRP-322).. If time permits, complete and submit an Emergency Use Request Form and Worksheet Emergency Use (HRP-322) to hsro@miami.edu and call the HSRO at 305-243-3195. During evenings or weekends you can call one of the IRB Chairs to discuss the emergency use. 

    Step Four

    If time permits, you must obtain informed consent from the patient using TEMPLATE CONSENT DOCUMENT – Emergency Use (HRP 502h).   If the patient is not able to provide informed consent due to incapacity and there is insufficient time to obtain consent from a legally authorized representative, see the Exception from the Requirement for Informed Consent for Emergency Use below.  

     

    Step Five

     You must report the use of the unapproved drug, biologic or device to the IRB through an eProst submission within five business days using the electronic Report of New Information SmartForm in eProst.  Regulations require that you submit this report even when you discussed the use of the investigational product with the sponsor and IRB Chair. If you fail to submit the report within five days, you will be restricted from submitting new Human Research until the IRB receives this report and your action plan to ensure you submit timely emergency use reports in the future.

     

    Step Six 

    Complete and submit the IND or IDE application to the FDA.  For IND, use FDA Form 3926.  For IDE, look here for information:

     

    Step Seven

     Finally, according to the FDA, the emergency use provision can be used only once.  If there is any possibility that you will need to use the same investigational product with the same patient or with a different patient, you must submit a protocol to the IRB and obtain an IND or IDE from the FDA.  The FDA regulations have provisions for expanded access use through a treatment protocol.  See

    FDA Guidance on Expanded Access for additional information. 

  • Exception to Informed Consent Requirement for Emergency Use

    The FDA regulations allow the use of an investigational product without informed consent when the investigator and a physician who is not involved in the study, both certify the following in writing: 

     

    1. The human subject is confronted by a life-threatening situation necessitating the use of the test article;
    2. Informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from the subject;
    3. Time is not sufficient to obtain consent from the subject's legal representative; and
    4. There is available no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject.

     

    If the investigator is not able to obtain the second opinion due to time constraints and the above requirements are met, the investigator must:

     

    1. Make and document the required determinations above;
    2. Have a physician who is not part of the research review and evaluate the documentation;
    3. Have the physician sign the document indicating his/her concurrence;
    4. Submit the document to the IRB by completing an electronic Report of New Information SmartForm through eProst within five business days.
    5. If the Investigational product is a device, the investigator must submit a report of the use of the product without informed consent to the sponsor within five business days.

     

    This process is described in “SOP: EMERGENCY AND TREATMENT USE OF INVESTIGATIONAL DRUGS, BIOLOGICS AND DEVICES (HRP-23).”

  • Treatment (Compassionate) Use

    Under FDA regulations (21 CFR § 312.300), expanded access (often referred to as “treatment use” or “compassionate use”) is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device). This access is for treatment outside of a clinical trial when no comparable or satisfactory alternative therapy options are available. Even though expanded access is not a clinical investigation, FDA submission and IRB review are required.

    The IRB will require an eProst submission for initial review. This submission must include at least:

    • Protocol
    • If the investigational product will be used in only one patient, the IRB will need redacted information demonstrating the patient’s need for the product.
    • TEMPLATE CONSENT DOCUMENT – Emergency Use (HRP 502h) revised to indicate the use is for non-emergency treatment use
    • Information about the investigational product such as an investigator brochure

    If the need for the investigational product is urgent, the IRB will forego the requirement for a formal protocol but will require sufficient information to make the determinations required under 21 CFR § 56.111. In these instances, the IRB will require:

    • Information about the efficacy and risks of the investigational product
    • Information about the patient’s condition supporting a finding that the patient has a condition for which no other comparable treatment or therapy is available
    • FDA approval of use of the investigational product for that patient (IND or IDE)
    • The procedures the physician will follow when using the investigational product, including the procedures to monitor patient safety during and after use of the investigational product.

     

    Click HERE for information about the FDA’s requirements.

  • Right to Try

    The “Right to Try Act” (H.R.878 - Right to Try Act of 2017) allows investigational drugs, biological products or devices without FDA approval under the following conditions:

    • To be eligible for “Right to Try,” the patient must:
      • Be diagnosed with a life-threatening disease or condition;
      • Have exhausted approved treatment options and is unable to participate in a clinical trial involving the eligible investigational drug (this must be certified by a physician who is in good standing with their licensing organization or board and who will not be compensated directly by the manufacturer for certifying);
      • The subject or their LAR must provide written informed consent for use of the investigational drug;
    • The investigational drug or biologic must meet the following criteria:
      • A Phase 1 clinical trial must have been completed;
      • The drug/biologic/device must not have been approved FDA approved for any use;
      • One of the following must be met:
          • An application has been filed with the FDA;
          • The drug/biologic is undergoing a clinical trial subject to an IND that is intended to provide data to support FDA;
      • Clinical trials are ongoing and have not been discontinued or placed on hold by the FDA. 

     

    UM strongly encourages the use of the expanded use pathway initiated by the FDA (described above) instead of Right to Try. Therefore, physicians should gently inform patients who invoke the Right to Try Act of the following:

    • The Act does not require institutions to accede to requests for unapproved drugs
    • UM follows Federal research regulations, and
    • Efforts to obtain unapproved drugs should be made to the FDA under its emergency use expanded access program.