1. Purpose
This SOP outlines the requirements for emergency uses of investigational drugs or biologics, emergency uses of unapproved medical devices, and exceptions to the requirements for informed consent in emergency situations.
2. Overview
The emergency use provision in FDA regulations is an exemption from the requirements for prior review and approval of research by the IRB. The exemption, which must meet the specific conditions described in the regulations, allows for one emergency use of an investigational drug or biologic or unapproved medical device in a life-threatening situation for which no standard acceptable treatment is available and when there is not sufficient time to obtain IRB approval
3. General Information
3.1. The emergency use of an investigational drug or biologic or unapproved medical device in research involving human subjects as defined by FDA regulations. All emergency uses are subject to the requirements of the WVU OHRP, except as described by this policy. Note: The emergency use of a drug, biologic, or device does not meet the DHHS definition of research involving human subjects. For more information on activities that are defined by FDA and DHHS regulations as “research involving human subjects,” please see SOP 011: Human Subject Research Determination.
3.2. The use of a marketed drug, biologic, or medical device for an indication that is not listed in the FDA-approved product labeling (i.e., “off label” use) for an individual in a lifethreatening situation does not constitute an emergency use as defined by FDA regulations and WVU OHRP policy. Regulations and university policy do not limit the authority of physicians to provide such emergency “medical care” to patients in life-threatening situations; however, physicians and other healthcare providers are responsible for complying with applicable state laws and institutional requirements regarding all uses of drugs, biologics, and medical devices
3.3. The use of a marketed drug, biologic, or medical device for an indication that is not listed in the FDA-approved product labeling (i.e., “off label” use) for an individual in a lifethreatening situation does not constitute an emergency use as defined by FDA regulations and WVU OHRP policy. Regulations and university policy do not limit the authority of physicians to provide such emergency “medical care” to patients in life-threatening situations; however, physicians and other healthcare providers are responsible for complying with applicable state laws and institutional requirements regarding all uses of drugs, biologics, and medical devices
4. Criteria for Emergency Use
4.1. According to FDA regulations, the emergency use exemption may be used if all of the following conditions are met
- According to FDA regulations, the emergency use exemption may be used if all of the following conditions are met
- A test article is any drug, biologic, or medical device for human use, or human food additive, color additive, electronic product, or any other article subject to FDA regulations
- The individual for whom the test article is intended is in a life-threatening situation
- To meet the criteria for life-threatening a condition does not have to be immediately life-threatening or immediately resulting in death
- Life-threatening also includes “severely debilitating”
- Severely debilitating does not include “pre-existing” (e.g., chronic) diseases or conditions with major morbidity
- No standard acceptable treatment is available
- Also, the individual for whom the test article is intended does not meet the enrollment criteria for an existing IRB-approved study or an approved study does not exist
- There is not sufficient time to obtain IRB approval
- An intervention is needed before review at a convened meeting of the IRB is feasible.
5. Prior Notification of Emergency Use
5.1. The IRB Chair (or physician designee) of the appropriate IRB, will be notified of a physician/researcher’s intent to use an investigational drug or biologic or unapproved medical device for emergency use. Notification may be made in person, electronically, or in writing. Researchers will provide the following information to allow the IRB Chair (or physician designee) to determine that FDA requirements for emergency use are met:
- Explanation of life-threatening situation necessitating the emergency use
- Description of standard treatment(s) previously used and/or why available options are not acceptable
- Investigational drug or biologic or unapproved medical device to be used
- If available, IND or IDE number of the drug, biologic, or device. Note: It is important to distinguish between emergency use INDs or IDEs and other types of expanded If available, IND or IDE number of the drug, biologic, or device. Note: It is important to distinguish between emergency use INDs or IDEs and other types of expanded
5.2. An IRB Chair’s acknowledgement of the emergency use does not constitute an IRB
approval of the clinical investigation. The researcher’s notification is used by
the IRB and the WVU OHRP to confirm that the proposed use meets FDA requirements
and to assist the researcher with filing the required report within the five-day
timeframe required by FDA regulations.
5.3. If the IRB Chair (or physician designee) determines there is adequate time to
schedule an IRB sub-committee for the prospective IRB concurrence of the emergency
use of an investigational drug, biologic, or unapproved medical device, a meeting
is scheduled as soon as possible so that the emergency use is not unnecessarily
delayed. Note: In this instance, the physician/researcher is still required (per
the Reporting Requirements section below) to notify the IRB in the form of a written
report within five working days after the emergency use of the investigational
drug, biologic, or unapproved medical device.
5.4. If the IRB Chair (or physician designee) determines there is not adequate time
to schedule an IRB sub-committee for the prospective IRB concurrence of the emergency
use of an investigational drug, biologic, or unapproved medical device, the IRB
Chair (or physician designee) acknowledges the emergency use based on FDA’s definition
of criteria for emergency use (see Section 5), and the required report (see Reporting
Requirements section) will be forwarded to the next available convened meeting
for review and concurrence of the IRB Chair’s (or physician designee’s) acknowledgement
of the emergency use.
5.5. If the IRB Chair (or physician designee) determines there is not adequate time to schedule an IRB sub-committee for the prospective IRB concurrence of the emergency use of an investigational drug, biologic, or unapproved medical device, the IRB Chair (or physician designee) acknowledges the emergency use based on FDA’s definition of criteria for emergency use (see Section 5), and the required report (see Reporting Requirements section) will be forwarded to the next available convened meeting for review and concurrence of the IRB Chair’s (or physician designee’s) acknowledgement of the emergency use.
7. Exception to the Requirements for Informed Consent
7.1. When informed consent cannot be obtained, both the physician/researcher and a physician who is not otherwise involved in the emergency use must confirm, in writing, that all of the following conditions apply:
- The subject is confronted by a life-threatening situation necessitating the use of the investigational drug or biologic or unapproved medical device.
- Informed consent cannot be obtained because of an inability to communicate with or obtain informed consent from the patient/participant.
- Time is not sufficient to obtain informed consent from the patient/participant’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 subject’s life.
7.2. If time is not sufficient to obtain an independent physician’s determination that the criteria for an exception to the requirements for informed consent (described above) are met, and in the physician/researcher’s opinion the immediate use of the investigational product is required to preserve the subject’s life, the physician/researcher must do both of the following:
- Verify in writing that the four conditions for an exception to the requirements for informed consent apply
- Obtain an independent review and evaluation of the physician/researcher’s determination in writing within five working days by a physician who is not otherwise involved in the emergency use
7.3. The IRB must be notified of the exception within five working days after the emergency use, as described below (see Reporting Requirements section)
8. IND Requirements for Emergency Uses of Drugs and Biologics
8.1. The emergency use of an investigational drug or biologic requires an IND. To obtain an emergency use IND, a physician/researcher should contact the product manufacturer or sponsor to determine if the investigational drug or biologic can be made available for the emergency use under the company’s IND.
8.2. Alternatively, if the manufacturer/sponsor will not provide the investigational product under its IND, a physician/researcher may contact FDA directly to obtain authorization for the company to ship the drug or biologic for the specific emergency situation in advance of an IND submission. For more information, please see FDA Contacts for Obtaining an Emergency IND.
8.3. Some manufacturers or sponsors will agree to the emergency use of an investigational drug or biologic, but require an “IRB approval letter” before shipping the product. When necessary, following the IRB Chair’s review and acknowledgement of the emergency use as described above in “Prior Notification of Emergency Use," WVU OHRP staff will provide the physician/researcher with documentation acknowledging that the IRB is aware of the intended emergency use and considers the use to meet FDA requirements
9. Additional Requirements for Emergency Uses of Unapproved Devices
9.1. FDA approval prior to emergency use or shipment of an unapproved medical device
is not required. The emergency use may involve a device that does not have an existing
IDE, a device used in a way that is not approved under an existing IDE, or a physician
who is not named as an investigator to the IDE. Whenever possible, authorization
should be obtained from the sponsor (if an IDE exists for the device) before the
emergency use.
9.2. In addition to determining that the criteria for emergency use are met, physicians/researchers
are required by FDA to assess the potential for benefit from the use of an unapproved
device and to have “substantial reason” to believe that benefits will occur. Whenever
possible, an independent assessment of the circumstances prior to emergency use
should also be obtained from a physician who is not otherwise involved in the emergency
use.
9.3. If the device has an existing IDE and the physician/researcher could not obtain authorization from the sponsor prior to the emergency use, the physician/researcher is responsible for reporting to the sponsor within five working days. The emergency use of an unapproved device must be reported to FDA by the sponsor (if an IDE exists for the device) within five working days of the time the sponsor learns of the use. If no IDE exists, the physician/researcher is responsible for reporting the emergency use directly to FDA. The physician/researcher’s follow-up report should contain the information described below.
10. Reporting Requirements
10.1. Physicians/researchers are responsible for notifying the IRB in writing within five working days after the emergency use of an investigational drug or biologic or unapproved medical device. Reports should be sent to the WVU OHRP with the following information:
- Investigational drug or biologic or unapproved medical device used
- IND number of the drug or biologic or IDE number (if one exists) of the device
- Date(s) of administration of the investigational product
- Explanation of the life-threatening situations necessitating the emergency use
- Demographic information of the patient/participant (e.g., age, gender, etc.) without personally identifiable information
- Outcome(s) of the emergency use
- An unsigned copy of the consent document that was used
- Alternatively, if consent was not obtained, either of the following as described above (“Exception to the Requirements for Informed Consent”):
- The physician/researcher’s and independent physician’s verification prior to the emergency use that the conditions were met for the exception to the requirements for informed consent
- The physician/researcher’s verification that the conditions for exception were met and independent physician’s review and evaluation (within 5 working days of the emergency use) of the physician/researcher’s determination
10.2. WVU OHRP staff will schedule the review of emergency use reports on the next
available convened IRB agenda (within 30 calendar days) to determine that the circumstances
met FDA requirements. If the convened IRB determines that the use failed to meet
regulatory requirements, the convened IRB will determine if noncompliance occurred
as described in SOP 049: Noncompliance and Research Misconduct. Physicians/researchers
will be notified by WVU OHRP staff of the outcome of the convened IRB’s review
and determinations within 14 calendar days of the review.
10.3. Physicians/researchers are also responsible for reporting the circumstances of the emergency use to the product manufacturer or sponsor of the investigational drug or biologic or unapproved medical device when the emergency use was performed under the manufacturer’s/sponsor’s IND or IDE. Otherwise, the emergency use is reported directly to the FDA. The follow-up report should contain the following information:
- Summary of the conditions constituting the emergency
- Acknowledgement by the IRB Chair or IRB sub-committee of prior notification of the emergency use
- Whether informed consent was obtained or the conditions were met for the exception to the requirements for informed consent
- Independent assessment by a physician not otherwise involved in the emergency use (when applicable)
- Outcome(s) of the emergency use
- Other information as required by the product manufacturer or sponsor
10.4. Physicians/researchers and IRBs are responsible for reporting and review of
any adverse events, unanticipated problems involving risks to subjects or others,
or other events associated with the emergency use, as described by SOP 031: Research
Related Event Reporting and SOP 034: Reporting to External Agencies.
10.5. Physicians/researchers who obtain an IND or IDE for the emergency use or subsequent use of the investigational drug or biologic or unapproved medical device are responsible for complying with FDA requirements for the use of investigational drugs and devices, including providing progress and/or final reports. See FDA’s website for regulations on Investigational New Drug Application and Investigational Device Exemptions guidelines.
11. Limitations of Emergency Use
11.1. The emergency use exemption allows for a single use or single “course of treatment”
(e.g., multiple doses of an antibiotic) of an investigational drug or biologic
or unapproved medical device without prior IRB review. FDA regulations require
that any subsequent use of the investigational product at the same institution
receive IRB review and approval before the product is used again.
11.2. FDA guidance acknowledges that it would be inappropriate to deny emergency
treatment to a second individual “if the only obstacle is that the IRB has not
had sufficient time to convene a meeting” to review the request. Physicians/researchers
are encouraged to evaluate the likelihood of a similar need occurring again, and
if future use is likely, immediately initiate efforts to obtain IRB review and
approval of a protocol to permit further use of the investigational drug, biologic,
or device.
11.3. Emergency use of an investigational drug or biologic or unapproved medical device must be differentiated from “Planned Emergency Research” in life-threatening situations. Planned emergency research is research conducted in emergency settings with subjects who cannot provide informed consent because of their life-threatening medical conditions (e.g., comparisons of methods for treating acute ischemic strokes) and who do not have an available legally authorized representative. Unlike emergency uses, planned emergency research must be approved in advance by FDA (or DHHS) and the IRB and publicly disclosed to the community in which the research will be conducted. For more information about the requirements for planned emergency research, please see SOP 054: Planned Emergency Research.
12. References
WVU Policies:
SOP 011: Human Subject Research Determination
SOP 022: Research Involving Investigational Drugs
SOP 023: Research Involving Investigational Devices
SOP 031: Research Related Event Reporting
SOP 034: Reporting to External Agencies
SOP 049: Noncompliance and Research Misconduct
Federal Regulations:
21 CFR 56.104
21 CFR 56.109 (c)
21 CFR 56.109 (c)
AAHRPP:
Element I.7.C