Current Status: Active PolicyStat ID: 4870880 Origination: 04/2018 Effective: 04/2018 Approved: 04/2018 Last Revised: 04/2018 Expiration: 04/2021 Owner: Policy Area: References: Suzanne Sharland-Hemmila: IRB Coordinator Institutional Review Board Applicability: U P Health Emergency/Compassionate Use or Single-Patient Use of Investigational Drugs, Biologics and/or Devices (IRB5580-020) PURPOSE The purpose of this policy is to offer UP Health System-Marquette (UPHS-M) Institutional Review Board guidance on the use of an investigational drug, biologic and/or device in a life-threatening situation for us of compassionate reasons. SCOPE This policy applies to both internal and external research administrators, investigators, research staff, IRB members and IRB staff. DEFINITIONS Emergency Use is defined as the use of an investigational drug, biologic and/or device with a human subject 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 (21 CFR 56.102(d)). The emergency use provision in the FDA regulations is an exemption from prior review and approval by the IRB. The exemption, which may not be used unless all of the conditions described in 21 CFR 56.102(d) exist, allows for one emergency use of an investigational article without prospective IRB review. FDA regulations require that any subsequent use of the investigational article at the institution have prospective IRB review and approval. FDA acknowledges, however, 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 issue. Life-threatening for the purpose of section 56.102(d), includes the scope of both life-threatening and severely debilitating, as defined below: (Serious) Life-threatening disease or condition means: (1) diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and (2) diseases or conditions with potentially fatal outcomes, where the endpoint of clinical trial analysis is survival. Severely debilitating means 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. Single- Patient Use (Compassionate) the phrase "compassionate use" is commonly used to describe some of the ways of making unapproved products available to patients; there is no FDA regulation or policy Page 1 of 6
defining "compassionate use." Compassion, intent to help, should be, and is, an element of all drug/biologic/ device investigation activities. In general, these uses of drug/biologic/devices are described as "treatment uses," because their intent is to provide treatment of patients, not primarily to evaluate the safety and effectiveness of the drug/biologic/devices, the primary and usual purpose of studies under an Investigational New Drug Application (IND). FDA refers to "compassionate use" requests for individual patients as a "single patient IND" study; wider use would usually take place under a "treatment IND" or "treatment protocol" under an existing commercial IND. A "single patient use" allows a physician to obtain access to an investigational drug/biologic/device for the treatment of a single patient. Usually, the patient is in a desperate situation and unresponsive to other therapies, or in a situation where no approved or generally recognized treatment is available. Further, there is usually little evidence that the proposed therapy is useful, but may be plausible on theoretical grounds or anecdotes of success. POLICY: "Emergency Use" of Investigational Drugs, Biologics and/or Devices It is the policy of U P Health System Marquette (UPHS-M) and the UPHS-M Institutional Review Board (IRB) to allow "emergency use of an investigational drug, biologic and/or device" providing regulatory criteria are met for an emergency use exemption, based on the following conditions: 1. Life-threatening situation or severely debilitating situation 2. No standard acceptable treatment available 3. Not sufficient time to obtain IRB approval 4. Report to the IRB within 5 working days of use 5. Any subsequent use of the test article is subject to IRB review 6. The activity is not a systematic investigation designed to develop or contribute to generalizable knowledge PROCEDURE: "Emergency Use" of Investigational Drugs, Biologics and/or Devices- The following will apply: Investigators will notify the IRB within five (5) working days of emergency use, even if the investigator notified the IRB prior to use and will include in the notification: 1. Justification for "emergency" use, 2. The consent document and process, 3. Why prospective reporting was not feasible (if applicable) 4. For investigational drugs, biologics and/or devices, documentation of FDA authorization pursuant to 21 CFR 312, Subpart I. The IRB chair or physician IRB member will evaluate whether the circumstances meet the criteria for the emergency use exemption and whether the informed consent process meets regulatory criteria and document their findings. Clarification may be obtained from the investigator if necessary. The IRB chair, physician IRB member, or an IRB administrator notifies the investigator of the determination once made. This notification should not be construed as IRB approval. If the investigator notified the IRB prior to use; the IRB chair, designated physician IRB member, or IRB administrator will initiate tracking to follow-up with the investigator to assure that the investigator files a report to the IRB within five (5) working days. If the investigator is not able to obtain informed consent of the subject or the subject's legally authorized Page 2 of 6
representative prior to emergency use of the investigational drug, biologic and/or device, the investigator's report must include a certification from a physician who is not otherwise participating in the clinical investigation as to how the use met the criteria for exception from informed consent in 21 CFR 50.23(a) (c). See details below under "Exception from Informed Consent Requirement." Reports of emergency use will be provided to the IRB at a regularly scheduled IRB meeting. Any noncompliance with the criteria for emergency use will be reviewed. If the activity is subject to U.S. Department of Health and Human Services regulations: Patients receiving an investigational drug, biologic and/or device in an emergency use as defined by FDA regulation may not be considered a research subject Data obtained from patients cannot be classified as human subject research Outcome of such care cannot be included in any report of research activity If the activity is subject to FDA regulations, emergency use of the investigational drug, biologic and/or device is considered to be a clinical investigation, the patient is a subject, and the FDA may require data from an emergency use to be reported in a marketing application. If the investigator plans subsequently to use the investigational article, he or she must submit an initial application to the IRB for review and approval prior to such use. Any subsequent use of the investigation article is subject to IRB review. Exception from Informed Consent Requirement Even for an emergency use, the investigator is required to obtain informed consent from the subject or the subject's legally authorized representative (LAR) in accordance with 21 CFR 50 (such as providing all required and appropriate additional elements of disclosure) and document consent in writing in accordance with 21 CFR 50.27 (obtaining a signed and dated consent document consistent with the short or long form regulatory requirement) unless both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following (21 CFR 50.23(a)): 1. The human subject is confronted by a life-threatening situation necessitating the use of the investigational drug, biologic and/or device. 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. 4. There is no available alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject. A report by the investigator and a physician who is not otherwise participating in the clinical investigation's written certification must be submitted to the IRB within five (5) working days after the use of the investigational drug, biologic and/or device. The IRB chair or designated physician IRB member will review the five (5) working day report to determine if the regulatory requirements in 21 CFR 50.23(a) have been met. If, in the investigator's opinion, immediate use of the investigational drug, biologic and/or device is required to preserve the subject's life, and if time is not sufficient to obtain an independent physician's determination that the four conditions above apply, the clinical investigator should make the determination and, within five (5) working days after the use of the drug, biologic and/or device, have the determination reviewed and evaluated in writing by a physician who is not participating in the clinical Page 3 of 6
investigation. 21 CFR 50.23(b). The independent evaluation must be submitted to the IRB within the five (5) working days' time period. 21 CFR 50.23(c). The IRB chair or designated physician IRB member will review the five (5) working day report to determine if the regulatory requirements in 21 CFR 50.23(a) 21 CFR 50.23(c) have been met. POLICY: "Single Patient Use" of Investigational Drugs, Biologics and/or Devices It is the policy of U P Health System Marquette (UPHS-M) and the UPHS-M Institutional Review Board to allow "single - patient use of an investigational drug, biologic and/or device" providing regulatory criteria are met based on the following conditions: 1. The patient is in a desperate situation and unresponsive to other therapies, or 2. The patient is in a situation where no approved or generally recognized treatment is available. 3. Further, there is usually little evidence that the proposed therapy is useful, but may be plausible on theoretical grounds or anecdotes of success. 4. Access to an investigational drug, biologic and/or device for use by a single, identified patient will be gained either through the sponsor under a treatment protocol, or through the FDA, by first obtaining the drug, biologic and/or device from the sponsor, and then submitting a treatment IND to the FDA requesting authorization to use the investigation drug, biologic and/or device for treatment use (21 CFR 312.35) Submissions For Treatment Use PROCEDURE: "Single-Patient Use" of Investigational Drugs, Biologics and/or Devices Processing a Request for Single - Patient Use/Compassionate Use: 1. When a physician would like to treat an individual patient using an unapproved drug, biologic and/or device the physician should first ensure that the manufacturer of the unapproved drug, biologic and/or device is willing to provide the drug, biologic and/or device. If the manufacturer agrees to provide the drug, biologic and/or device, the physician should submit an IND to the FDA. 2. The criteria are the same for a Single Patient IND and Emergency Use IND, except that for an Emergency Use, there is insufficient time to obtain prior IRB approval. 3. FDA regulations 21 CFR 312.305 and 21 CFR 312.310 permits an investigational drug, biologic and/or device to be used for the treatment of an individual patient by a licensed physician, under the following circumstances. A. The patient has a serious or immediately life-threatening disease or condition; a. Immediately life-threatening disease or condition means a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment. b. Serious disease or condition means 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. B. There is not comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; Page 4 of 6
C. The potential patient benefit justifies the potential risks of the treatment use; D. The potential risks are not unreasonable in the context of the disease or condition to be treated; E. The probable risk to the patient from the investigational drug, biologic and/or device is not greater than the probable risk from the disease or condition F. The patient cannot obtain the drug, biologic and/or device under another IND or protocol; and G. Providing the investigational drug, biologic and/or device for the requested use will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use. Please refer to the FDA's website on "Physician Request for an Individual Patient IND under Expanded Access for Non-Emergency or Emergency Use" for more information. 4. If the situation satisfies the FDA criteria for single - patient use, the next step is to determine whether an IRB acknowledgment letter (versus an IRB approval letter) is what the sponsor requires. 5. If the situation fits the criteria for single - patient use and the sponsor requires an acknowledgement letter, follow these procedures for an emergency-use exemption as described: A. The investigator will generate a letter to the IRB chair describing the single patient use situation. The letter must document compliance with specific FDA requirements for emergency use as indicated in #3. (Sample Addendum #1) B. The notification to the IRB must occur before use of the investigational articles. C. The IRB chair or appropriate designee (IRB member with appropriate medical knowledge) reviews the investigator's letter and confirms that (1) an emergency situation exists and that (2) there is not sufficient time to convene a full-board IRB meeting. D. The IRB office generates a letter to be signed by the IRB chair (or designee) acknowledging notification of emergency use of the investigational article. (Sample Addendum #1) E. The IRB letter should indicate only knowledge of, acknowledgement of, or appropriate notification of the use of the investigational article. The IRB letter should not indicate IRB review or approval. F. All subsequent uses of the test article should be reviewed using the standard full-board IRB review process. If an investigator believes another request for the use of this investigational article is forthcoming, the full IRB review process should be initiated. The FDA acknowledges that subsequent uses should not be denied because the IRB could not convene in a timely manner. The IRB letter to the investigator should also describe the FDA subsequent-use requirement. G. If the situation does not meet FDA criteria for emergency use, a convened full-board IRB review and approval of the protocol and consent form per standard IRB review procedure must be completed before release of the investigational article. H. If the sponsor requires IRB approval before release of the investigational article, an IRB approval letter may only be written after a convened full-board review and approval of the protocol and the consent form according to standard IRB procedure. I. No type of expedited or subcommittee process is allowed for IRB review and approval of the emergency use of an investigational article, according to federal regulations. REFERENCES 21 CFR 50.27 Documentation of Informed Consent 21 CFR 56.102 Institutional Review Boards Page 5 of 6
21 CFR 312 Investigational and New Drug Application Policy Effective Date: 11/13/13 Policy Revisions: 07/15 Attachments: Compassionate Use Document- IRB5580-0020.docx Compassionate Use Letter IRB Chair to MD- IRB5580-0020.docx Compassionate Use Letter MD to IRB Chair-IRB 5580-0020.docx Approval Signatures Step Description Approver Date Wael Khouli: Chief Medical Officer 04/2018 Rudolph Evonich: Physician 04/2018 Dianna Larson: Director of Research 04/2018 Suzanne Sharland-Hemmila: IRB Coordinator 04/2018 Applicability U P Health Page 6 of 6