This guidance is specific to the single patient non-emergent and emergency expanded access use of an unapproved investigational drug, biologic, or device.
Expanded Access, Non-Emergency Use
The FDA allows for expanded access of unapproved drugs, biologics, and devices outside of a clinical trial for patients with serious diseases or conditions when there is no satisfactory alternative therapy to treat the patient’s disease or condition. This is sometimes referred to as compassionate use or treatment use. The terms expanded access and compassionate use are often used interchangeably. FDA submission and IRB review are required even though expanded access is not clinical research.
All of the following conditions must exist to justify the expanded access of an unapproved investigational drug, biologic, or device:
- The patient has a life-threatening or serious disease or condition;
- There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; and
- Potential patient benefit justifies the potential risks of the investigational device.
- Patient taking the investigational medical product will not affect the investigational trials. (drugs/biologics only)
In addition to the above conditions, the following determinations must also be made for drugs/biologics:
- The physician must determine that the probable risk to the person from the investigational drug is not greater than the probable risk from the disease or condition; and
- FDA must determine that the patient cannot obtain the drug under another IND or protocol.
Immediately life-threatening disease or condition - a stage of 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.
Serious disease or condition - a disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one.
Single patient, non-emergency expanded access requests require IRB review and approval under FDA regulations. Investigator initiated single patient expanded access IND/IDE requests will be processed through PittPRO. Please see the IND and IDE Support (IIS) website for information about preparing an IND/IDE submission to FDA. Industry sponsored single patient non-emergent expanded access and IND/IDE treatment protocols must be processed through the UPMC OSPARS office.
Expanded Access, Emergency Use
The FDA permits emergency use of a test article on a human patient in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval. Although prospective IRB approval is not required for emergency use per FDA regulations, treating physicians are highly encouraged to reach to the IRB for guidance. All of the conditions listed for non-emergency must also be met for emergency use.
- It is the physician’s responsibility to determine whether the criteria for emergency use have been met, to assess the potential for benefits from the emergency use of the drug or device, and to have substantial reason to believe that benefits will exist.
- The physician may not conclude that an “emergency” exists in advance of the time when the treatment may be needed, solely on the expectation that IND or IDE approval procedures require more time than available.
- Physicians should be aware that the FDA expects them to exercise reasonable foresight with respect to potential emergencies and to make appropriate, advance arrangements under Expanded Access, Treatment IND, or IDE procedures to avoid creating a situation where such arrangements are impracticable.
|Drugs and Biologics||Devices|
|Prospective manufacturer authorization required||Yes||Yes|
|Prospective FDA approval required||Yes||No (IDE report to FDA within 5 days of using of the investigational device)|
|Prospective IRB approval required||No (but strongly encouraged) If no prospective IRB approval, then the IRB must be notified within 5 working days||No (but strongly encouraged) if no prospective IRB approval, then the IRB must be notified within 5 working days|
|Prospecitive informed consent required||Yes (or LAR if patient is unable to consent for self)||Yes (or LAR if patient is unable to consent for self)|
All emergency single patient expanded access requests, regardless of who will act as sponsor, will be submitted via PittPRO. Those seeking an emergency use should refer to the FDA Information Sheet for for Emergency use of an Investigational Drug or Biologic and the website, Emergency IND Timeline for step by step instructions or Expanded Access for Medical Devices (IDEs) for detailed information.
Procedures for Submission for Emergency Use of Unapproved Investigational Drug, Biologic, or Device:
Obtain authorization from the manufacturer
- For an unapproved investigational drug or biologic, contact the manufacturer of the investigational drug or biologic to determine if the manufacturer has an IND in place. If YES, see possible approaches below:
- Inquire if the manufacturer is willing to submit an emergency single patient IND protocol under the existing IND. In this scenario, the commercial manufacturer will sponsor the IND and the PI will act as the treating physician. A completed Form FDA 1572 as well as other information related to the patient’s status may be required by the manufacturer.
- If the manufacturer is unwilling to submit under the existing IND, inquire if they are willing to provide a letter of authorization (LoA) permitting FDA to refer to the company’s IND or IDE file to provide certain necessary information about the investigational medical product (e.g., chemistry, manufacturing, controls). This will allow the treating physician to request the single patient expanded access IND. In this scenario the treating physician will also sponsor the IND. The company should include their existing IND number for the investigational medical product in the LoA.
Note that the manufacturer will likely require the attending physician to contact the FDA to obtain emergency use of Emergency IND approval prior to supplying the investigational drug. The LoA should contain the responsible FDA review Division which is helpful in determining which Division to contact.
If no IND is on file at the FDA, inquire if the manufacturer has another pathway for securing FDA approval that will allow access the investigational product).
- For an unapproved investigational device, contact the manufacturer of the investigational device to determine if the manufacturer has an IDE in place. If YES, see possible approaches below:
- Inquire if the manufacturer is willing to submit an IDE supplement requesting approval for compassionate use to treat the patient. The manufacturer will require information related to the patient’s condition as well as other documents.
- If the manufacturer is unwilling to submit an IDE supplement, inquire if they are willing to provide a letter of authorization (LoA) permitting FDA to refer to the company’s IDE file to provide certain necessary information about the investigational device. The company should include their existing IDE number for the investigational device in the LoA.
- The requesting physician must notify the FDA of the emergency use of the device (i.e. within 5 days of the use of the device).
If time does not allow for the submission to be made in PittPRO or if the requester is unclear about the expanded access process, contact the IRB at (412) 383-1480 during normal working hours and for after hours, follow the instructions on the voice mail message to contact the IRB Chair or Vice Chair.
Submit the request in PittPRO (www.pittpro.pitt.edu)
- Click "Create New Study"
- Basic Information page, upload the requested FDA documents under #8
|Documents for Drugs and Biologics||Documents for Devices|
- Proceed to Study Scope #5, check "Emergency Use/Single Patient Access"
- Complete all pages in the application, including the Emergency Use/ Single Patient Expanded Access page.
- IRB Chair or Vice Chair will review and send a note via PittPRO to concur with the request or to request additional information.
- If IRB concurrence was not prospectively obtained, all the required documentation must be submitted within 5 working days. Documentation should include a summary of the intervention
- If the unapproved investigational drug or biologic emits ionizing radiation, the Radiation Safety Office (412-624-2728) must also be notified.
- University of Pittsburgh IRB policies require that the IRB be notified prior to emergency use when feasible. However, this notification of the IRB will NOT result in an IRB approval.
- Results from an emergency use of an unapproved investigational drug, biologic or device cannot be used as research data.
Written informed consent from the patient or the patient’s legally authorized representative must be obtained prior to the emergency use unless a waiver of informed consent is approved. If time permits, the IRB should review the consent form prior to consenting the patient.
The regulations do, however, provide for a waiver of informed consent if both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following:
- the subject 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 subject
- time is not sufficient to obtain consent from the subject’s legal representative
- no alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject’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 5 working days) a review of his/her determination by a physician not participating in the investigation. Documentation of this process should be submitted to the IRB within 5 working days.