Emergency
Use of Drugs or Biologics
Under
usual circumstances, the use of an investigational drug,
device or biologic requires prior approval of the IRB.
Rarely there are emergency circumstances where it is in
the best interests of a patient for an investigational
drug, device or biologic to be used without IRB review
and approval. Emergency use is defined as the use of an
investigational drug or biological product 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 [21
CFR 56.104(c)] 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 a test article without
prospective IRB review. FDA regulations require that any
subsequent use of the investigational product at an 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.
Investigators
should do the following:
- Determine if the proposed use meets the regulatory definition
for emergency use of an investigational drug or biologic
[21 CFR 56.102(d)]. Emergency uses must meet ALL of the
following criteria:
- The
subject has a disease or condition which is life-threatening
(e.g., the likelihood of death is high) or severely
debilitating (e.g., may cause irreversible morbidity,
such as blindness, loss of limb, loss of hearing, paralysis
or stroke);
- The
subject's disease or condition requires intervention
with the investigational drug or biologic before review
at a convened meeting of the IRB is feasible; and
- No
standard acceptable treatment is available.
- Contact manufacturer of drug/biologic to determine if
it can be provided under an existing IND or, if not available
through the manufacturer, contact the FDA for an Emergency
IND.
Practical
Tips: ·
- Useful
web sites:·
- Sometimes
the manufacturer will not entertain your request until
you have IRB acknowledgement, i.e. the Insight/eIRB emergency
use form reviewed and acknowledged by an IRB chair.
- "Piggybacking”
onto another investigator’s or sponsor’s existing IND
application is usually easier, because they will often
have a “package” of documents to send you. They must
list you as a co-investigator (sub-investigator) on
their IND.
- Contact the Partners Human Research Office at 617-424-4100
to notify them of planned emergency use of a
drug or biologic.
- If
you have never used a drug in this fashion, you are
strongly encouraged to speak personally with an IRB
chairperson and research pharmacist in order to assist
you with the process (see specific contacts below).
You have important regulatory and reporting requirements
with the FDA and IRB that must be followed.
- There
must be a staff physician (i.e. not a fellow or resident)
responsible for emergency uses; who oversees and is
responsible for the emergency use and completes all
reporting requirements.
- Contact the MGH Pharmacy (617-726-2515) or BWH
Investigational Drug Service (617-732-6410) as
soon as possible to inform them of the planned use and
shipment of drug.
- If
you are expecting an emergency use might
be necessary, please contact the research pharmacy and
IRB staff during regular business hours,
in order to get the regulatory process underway. It
is difficult if not impossible to attend to certain
matters, such as contact with the FDA or manufacturers
at night and on weekends.
- At
both institutions there are specific research pharmacists
with expertise in emergency uses who can assist you
(see contacts below), including weekend coverage.
- If
a protocol from any institution or manufacturer is being
followed, or other reference information regarding the
drug or biologic is available, a copy must be sent to
the IRB and the pharmacy. Any information regarding
drug use, indication, administration, dispensing instructions
(dose, route, frequency, etc), and preparation instructions
must be sent to the pharmacy. The pharmacy needs to
verify what is being prepared and the responsible physician
should have something in writing to this effect. The
pharmacist must be able to verify that the written order
is correct and that no transcription errors occurred,
(i.e. 1 mg vs. 1gm) before the drug can be released
from pharmacy.
- Obtain informed consent from subject or if incompetent
to give informed consent, the subject's legally authorized
representative (next-of-kin).
- If
the holder of the IND (i.e., sponsor or other local
or distant physician) has an existing patient consent
form that is made available, that form may be used.
The IRB would prefer to review these forms in advance
of their use, if time permits, though this may not be
possible in an emergency situation. Whenever possible,
written consent should be sought.
- If
there is no existing consent form available from a sponsor
or other IND holder, a clinical consent form should
be used. Physicians should discuss with patients, or
legally authorized representatives, the investigational
nature of the proposed emergency treatment, the risks
and benefits, and document these discussions in the
medical record, in clinical notes, and in a clinical
consent form.
- An exception to the
requirement for informed consent may be waived 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 (or
severely debilitating) situation necessitating the
use of the investigational drug or biologic;
- 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; and
- No
alternative method of approved or generally recognized
therapy is available that provides an equal or greater
likelihood of saving the subject's life.
- Investigational drugs should be delivered to the Research
Pharmacies at the respective hospitals, with the responsible
receiving physician’s name and contact information clearly
noted on the mailing label. Alert the pharmacy about the
expected arrival of the drug.
- The investigator must notify the Partners Human Research Committee (PHRC) within 5 working days after the use of the investigational drug or biologic product, or unapproved medical device.
Submit completed Insight/eIRB Emergency
Use Form within 5 working days after the use of the investigational drug or biologic.
Practical
Tip: Attach a brief letter with a clinical synopsis of
the patient if the information does not fit into the form.
CONTACTS
FOR EMERGENCY USES OF INVESTIGATIONAL DRUGS:
MGH
IRB Chair
Elizabeth Hohmann MD
Office 617-724-7532
Lab 617-724-8625; 6-0886
Office 617-726-3812
Pager PHS 28390
If
not available, see contacts at IRB web site for other IRB
chairs
MGH
Research Pharmacists
Contact
pharmacist covering your service; they can put you in
touch with covering research pharmacist.
Shipping
Address:
John
Vetrano R Ph
Research Pharmacy
Massachusetts General Hospital
55 Fruit St
Boston, MA 02114
Ph 617-726-2515
Fax 617-724-5013
BWH IRB Chairs
Elizabeth
Hohmann MD
Office 617-724-7532
Lab 617-724-8625; 6-0886
Office 617-726-3812
Pager PHS 28390
Julian Seifter MD
Office 617-732-7482
Pager PHS 11686
If
not available, see contacts at IRB web site for other chairs.
BWH
Research Pharmacists
Investigational
Drug Service Pharmacy
617-732-6410
(7am-8pm weekdays and 7am-5pm weekends)
IDS pharmacist on-call pager: 33672 (24 hours, 7 days)
Jon Silverman R Ph
Office: 617-732-6410 Pager: 33784
John Fanikos R.Ph.
Office: 617-732-7165
Cell: 617-605-3237
Pager: 11024
Main Pharmacy: 617-732-7153 (24 hours, 7 days)
Shipping Address:
IDS Pharmacy
Tower L2
75 Francis Street
Boston, MA 02115
Spaulding IRB Chair
Leslie Morse, DO
Office: 617-573-2200
Pager: 61153
Spaulding
Research Pharmacist
Stephen Kolaczkowski
Office: 617-573-2287
Spaulding Pharmacy Director
Samir Kobeissi
Office: 617-573-2285
Pager: 61158 (24-hours, 7 days) |