Download Emergency or Single - Patient - Compassionate

U P HEALTH SYSTEM – MARQUETTE
MARQUETTE, MICHIGAN
INSTITUTIONAL REVIEW BOARD
Subject: Emergency or Single - Patient
Policy No. : 20
(Compassionate) Use of Investigational Drugs,
Effective Date: 11/13/13
Biologics and/or Devices
Revision Date: 07/15
______________________________________________________________________________
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 lifethreatening 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.
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologics
and/or Devices, Page 2
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 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 –

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)
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologics
and/or Devices, Page 3
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 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.
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologic
and/or Devices, Page 4
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 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 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.
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologic
and/or Devices, Page 5
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.
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologic
and/or Devices, Page 6
A. The patient has a serious or immediately life-threatening disease or condition;
 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.
 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;
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:
Emergency or Single – Patient (Compassionate Use of Investigational Drugs, Biologic
and/or Devices, Page 7
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 fullboard 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.
Attachment #1: Template IRB and Physician letters
Attachment #2: Single - Patient Use Log
End of Policy
Attachment # 1 to IRB Policy #20 – Emergency or Single – Patient (Compassionate) Use of
Investigational Drugs, Biologic and/or Devices – Template IRB and Physician Letters
(Letterhead)
Date
Dear Dr. IRB chair name,
Please regard this notice as a request for an IRB Emergency-Use Exemption for the use of the (drug,
biologic, device) xxxx for one patient (initials).
According to FDA regulations, in order to qualify for an emergency-use exemption, the situation must
involve a “life-threatening situation in which no acceptable standard treatment is available and in which
there is not sufficient time to obtain full Institutional Review Board (IRB) approval.”
This situation complies with the definition because the patient (describe why the patient needs the drug,
biologic, device in a timely manner)…
Consent from the patient will be obtained…(explain the process so that the patient understands that the
drug, biologic, device is not FDA approved for this use and if a consent form will be used, state so and
include with this memo).
The data for this patient will not be used as part of a prospective research protocol.
Sincerely,
Dr. XYZ
Template letter from IRB to physician:
Dear Dr. Smith,
The office of the Institutional Review Board (IRB) has received your written notification of the request
for the one-time emergency-use exemption of the investigational drug, biologic, device xxxx, for one
patient, (initials).
Prior IRB review and approval are not required for the emergency use of an investigational article as
described in 21 CFR 56.102(d) and 21 CFR 56.104(c). This memo is not a notification of IRB review or
approval.
The notification you have provided to the IRB meets the requirements of our office and federal
regulations. Please note, if subsequent use of drug, biologic, device xxxx is anticipated, please submit an
application for review by the full IRB before its next use. The data from this use should not be used for
prospective research purposes.
Thank you,
IRB chair signature
Version: November 2013
Attachment #2 to Policy #20 – Emergency or Single – Patient (Compassionate) Use of Investigational Drugs, Biologics and/or Devices
Version: November 2013
Rec’d
Investigator
Brochure
Date of Use
Use
Acknowledg
ement if less
than 30 days
Investigational
New Drug
Approval Date
Copy of
Informed
Consent
Letter to
Physician
Letter from
Physician
Drug/Biologic
/Device
Patient
Initials
Physician
Name
[Type the document title]