Version
1.0
Date Updated
Wednesday, October 15, 2008
Descripton

Approved by: Interim Vice Chancellor for Research
AAHRPP REF#: 139
AAHRPP Elements: I.5.C


POLICY


  1. The stipulation for emergency use of a test article (i.e., investigational drugs, agents, biologics, or medical devices) in the FDA regulations represents an exemption from prospective IRB review and approval for the use in a single patient of an investigational drug, biologic or medical device that does not have premarket approval or other approval. Any subsequent use of the test article at the institution requires prospective convened IRB review and approval, unless emergency treatment to a second individual arises before the IRB has had sufficient time to convene a meeting to review the issue. (Refer to FDA Information Sheets: Emergency Use of an Investigational Drug or Biologic, 1998 Update). The IRB Chair (or designee) determines whether or not this condition has been met.
  2. The UIC IRB manages the emergency use of investigational drugs, biologics and medical devices in accordance with FDA regulations and UIC policies and procedures. The FDA and UIC policy exempt the requirement for review by the convened IRB in emergency use situations.
  3. UIC policy requires the investigator to notify the IRB and receive acknowledgement of the emergency use from the IRB Chair (or designee) before administering the test article. The Director of OPRS may substitute when the IRB Chair or designee is not available. The IRB Chair (or designee) reviews the application for emergency use and acknowledges whether or not they concur that administering the test article in this situation meets the emergency use requirements at 21 CFR 56.102(d)). The acknowledgement by the IRB does not represent approval as FDA regulations do not allow expedited approval of research in emergency situations. It should be noted that manufacturers’ policies typically require an acknowledgement or approval letter from the IRB before the test article will be shipped.
  4. Criteria for Emergency Use.
    1. The emergency use exemption for an investigational drug, biologic or medical device requires that each of the following criteria in 21 CFR 56.102(d) are satisfied:
      1. A life-threatening situation exists requiring treatment with the test article;
      2. No standard acceptable treatment is available;
      3. Insufficient time is available to obtain IRB approval at a convened meeting; and
      4. The activity is not a systematic investigation designed to develop or contribute to generalizable knowledge.
    2. The term “life-threatening” encompasses conditions that are both:
      1. Life-threatening: diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subject must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
      2. Severely debilitating: 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.
  5. Representation of the activity as research.
    1. Under FDA regulations, emergency use of a test article meets the FDA definition of a clinical investigation, and the patient receiving the test article meets the FDA definition of a human subject. Therefore, this activity qualifies as human subjects research under FDA regulations and the FDA may require data from emergency use of a test article to be reported in a marketing application.
    2. This activity does not however meet the DHHS criteria for human subjects research, as DHHS regulations at 45 CFR 46 do not allow research involving human subjects to be initiated without prior IRB review and approval. Therefore, UIC policy is that data from emergency use of a test article may not be reported as part of a prospective systematic investigation designed to develop or contribute to generalizable knowledge. Similarly, this FDA exemption from IRB review is not recognized as VA-regulated human subjects research.
    3. The above policy does not prevent the retrospective use of the data, provided appropriate IRB review and approval of this use has occurred, or the publication of a single patient case history.
  6. Requirement for Five-Day Follow-up Report. The emergency use of a test article must be reported to the IRB within five working days. (21 CFR 56.104(c)). The report is presented to the IRB at the next convened meeting. The IRB reviews the initial notification, five-day follow-up report, and other relevant information provided by the PI. The IRB Chair (or designee) serves as the primary reviewer on this meeting agenda item. The IRB acknowledges whether or not the emergency use of the test article meets the requirements of 21 CFR 56.102(d) and whether there are any further issues related to the treatment of the subject. The IRB’s determination is documented in the meeting minutes and communicated in writing to the investigator. When the emergency use involves the JBVAMC, the R&D Office also receives a copy of the IRB’s determination letter to disseminate to the R&D Committee and ACOS for R&D.
  7. Requirement for an IND for an Investigational Drug or Biologic. The emergency use of an investigational drug or biologic that does not have premarket approval or other approval requires an IND. The investigator must contact the manufacturer and determine if the drug or biologic can be made available for emergency use under the company's IND. When an IND does not exist and the situation does not allow time for submission of an IND, the FDA may authorize the shipment of the test article in advance of the IND submission. The request for such authorization may be made by telephone or other rapid communication means. (21 CFR 312.36). Contact information for obtaining an emergency IND is available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm126491.htm.
  8. Requirement for an IDE for an Investigational (Unapproved) Medical Device. An unapproved device may be used in human subjects only if it is approved for clinical testing under an approved application for an IDE. However, the FDA recognizes that emergencies arise where an unapproved device may offer the only possible life-saving alternative, but an IDE for the device does not exist, the proposed use is not approved under an existing IDE, or the physician or institution is not approved under the IDE. Using its enforcement discretion, the FDA has not objected if a physician chooses to use an unapproved device in such an emergency, provided that the physician later justifies to the FDA that an emergency actually existed.
    1. The requirements for emergency use of an unapproved device are similar to those for an investigational drug:
      1. The patient is in a life-threatening condition that requires immediate treatment;
      2. No generally acceptable alternative for treating the patient is available; and
      3. Because of the immediate need to use the device, there is no time to use existing procedures to get FDA approval for the use.
    2. The FDA expects the physician/investigator to follow as many human subjects protection procedures as possible, including:
      1. Obtaining an independent assessment by an uninvolved physician;
      2. Obtaining informed consent from the patient or a legal representative in accordance with, and to the extent required by, 21 CFR 50;
      3. Documenting informed consent in writing in accordance with, and to the extent required by, 21 CFR 50.27;
      4. Notifying institutional officials as specified by institutional policies;
      5. Notifying the IRB; and
      6. Obtaining authorization from the IDE holder, if an approved IDE for the device exists.
      7. UIC policy requires physician/investigators at a minimum to fulfill procedures 2, 4, and 5.
    3. After an unapproved device is used in an emergency use situation, the investigator should:
      1. Report to the IRB within five business days and otherwise comply with provisions of the IRB regulations (21 CFR 56);
      2. Evaluate the likelihood of a similar need for the device occurring again, and if future use is likely, immediately initiate efforts to obtain IRB approval and an approved IDE for subsequent use of the device; and
      3. If an IDE for the use does exist, notify the sponsor of the emergency use, or if an IDE does not exist, notify the FDA of the emergency use (CDRH Program Operation Staff 301-594-1190) and provide the FDA with a written summary of the conditions constituting the emergency, subject protection measures, and results. While prior approval for shipment or emergency use of the investigational device is not required, the use must be reported to the FDA by the IDE sponsor within five working days from the time the sponsor learns of the use. ((21 CFR 812.35(a)(2) and 812.150(a)(4)).
  9. Informed Consent in an Emergency.
    1. Even for emergency use of a test article, the physician/investigator is required to obtain and document informed consent from the subject or the subject's legally authorized representative in accordance with FDA regulations (21 CFR 50 subpart B) and Illinois state law. Therefore, a physician/investigator must prepare and submit a consent document with the request to the IRB chair (or designee) for emergency use of the test article. The UIC OPRS Emergency Use consent template form should be utilized.
    2. An exception to the requirement for informed consent is allowed if the physician/investigator and a physician who is not otherwise participating in the clinical investigation certify in writing that all of the criteria at 21 CFR 50.23(a) are met before (and/or after) the use of the test article:
      1. The subject is confronted by a life-threatening situation necessitating the use of the test article;
      2. Informed consent cannot be obtained 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. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject's life.
    3. If, in the physician/investigator’s opinion, immediate use of the test article is required to preserve the subject's life, and time is not sufficient to obtain an independent physician's determination that the four conditions above apply, the physician/investigator should make the determination as to the above four items and, within five business days after the use of the test article, have the determination reviewed and evaluated in writing by a physician who is not participating in the clinical investigation. (21 CFR 50.23(b)).
    4. In the five day follow-up report notifying the IRB of the emergency use of a test article, the physician/investigator must also inform and provide documentation to the IRB of any exceptions to the requirement for consent (21 CFR 50.23(c)) if this was not done at the time of notification of emergency use. The IRB will subsequently review and determine if the criteria for an exemption from IRB review and the exception for the requirement from consent has been met.
  10. Consequence of failure to comply with this policy or FDA requirements. If notification is not obtained prior to emergency administration of the test article or the five-day follow-up report is not submitted, the IRB may determine that the use of the test article did not meet the criteria for exemption from prospective IRB approval and represents serious and reportable noncompliance to the FDA. The IRB may also decide that the use represents reportable noncompliance when, after reviewing the report, it concludes that the requirements of 21 CFR 56.102(d) for emergency use or 21 CFR 50.23(a) for exception of informed consent are not met.