Expanded Individual Patient Access Application Submissions

Individual Patient Expanded
Access Applications:
Form FDA 3926
Guidance for Industry

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

June 2016
Updated October 2017
Procedural

OMB control number 0910-0814
Expiration Date: 04/30/2019
See additional PRA statement in section V of this guidance.

Individual Patient Expanded
Access Applications:
Form FDA 3926
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: [email protected]
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

and/or
Office of Communication, Outreach and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Bldg. 71, Room 3128
Silver Spring, MD 20993-0002
Phone: 800-835-4709 or 240-402-8010
Email: [email protected]
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

June 2016
Updated October 2017
Procedural

Individual Patient Expanded
Access Applications:
Form FDA 3926
Guidance for Industry
NOTE: FDA updated Section III of this guidance in October 2017 to clarify the IRB review
requirements for individual patient expanded access treatment use of investigational
drugs. The changes to Form 3926 are intended to allow for a waiver of the requirement
for review and approval at a convened IRB meeting if the physician obtains concurrence
by the IRB chairperson (or designated IRB member) before the treatment use begins.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

June 2016
Updated October 2017
Procedural

Contains Nonbinding Recommendations
TABLE OF CONTENTS

I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

A.

Expanded Access for an Individual Patient................................................................................. 3

B.

Emergency Expanded Access for an Individual Patient ............................................................ 5

III.
CONSIDERATIONS AND REGULATORY REQUIREMENTS IN REQUESTING
EXPANDED ACCESS FOR AN INDIVIDUAL PATIENT ..................................................... 5
IV.

PROCEDURES AND TIMELINE FOR PROCESSING FORM FDA 3926 .............. 6

V.

PAPERWORK REDUCTION ACT OF 1995 ................................................................ 7

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Individual Patient Expanded Access Applications:
Form FDA 3926
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the
title page.

I.

INTRODUCTION

This guidance describes Form FDA 3926 2 (Individual Patient Expanded Access –
Investigational New Drug Application (IND)), which is available for licensed physicians to use
for expanded access requests for individual patient INDs. The terms compassionate use and
preapproval access are also occasionally used in the context of the use of an investigational
drug to treat a patient; however, these terms are not defined or described in FDA regulations.
Individual patient expanded access allows for the use of an investigational new drug 3 outside
of a clinical investigation, or the use of an approved drug where availability is limited by a risk
evaluation and mitigation strategy (REMS), for an individual patient who has a serious or
immediately life- threatening disease or condition and there is no comparable or satisfactory
alternative therapy to diagnose, monitor, or treat the disease or condition. Form FDA 3926
provides a streamlined alternative for submitting an IND under 21 CFR 312.23 for use in cases
of individual patient expanded access, including for emergency use. This guidance and Form
FDA 3926 do not apply to other types of expanded access requests, including requests for
expanded access for medical devices.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of

1

This guidance has been prepared by the Office of the Commissioner, Office of Policy, Planning, Legislation, and
Analysis, in cooperation with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation
and Research at the Food and Drug Administration.
2

FDA forms are available on the internet at
https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm.
3

For the purposes of this guidance, the terms investigational new drug, investigational drug, drug, and drug product
refer to both human drugs and biological products regulated by the Center for Drug Evaluation and Research or the
Center for Biologics Evaluation and Research.

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the word should in Agency guidances means that something is suggested or recommended, but
not required.

II.

BACKGROUND

Expanded access refers to the use of an investigational drug when the primary purpose is to
diagnose, monitor, or treat a patient rather than to obtain the kind of information about the drug
that is generally derived from clinical trials. FDA has a long history of facilitating access to
investigational drugs for treatment use for patients with serious or immediately life-threatening
diseases or conditions4 who lack therapeutic alternatives. FDA revised its IND regulations in
20095 by removing the existing regulations on treatment use and creating subpart I of 21 CFR
part 312 to consolidate and expand the various provisions regarding expanded access to
treatment use of investigational drugs.
Subpart I describes the three categories of expanded access:
•

Expanded access for individual patients, including for emergency use (21 CFR 312.310)

•

Expanded access for intermediate-size patient populations (generally smaller than those
typical of a treatment IND or treatment protocol — a treatment protocol is submitted as a
protocol to an existing IND by the sponsor of the existing IND)6 (21 CFR 312.315)

•

Expanded access for widespread treatment use through a treatment IND or treatment
protocol (designed for use in larger patient populations) (21 CFR 312.320)

The revised regulations were, among other things, intended to increase awareness and knowledge
about expanded access and the procedures for obtaining investigational drugs for treatment use
for patients with serious or immediately life-threatening diseases or conditions who lack
therapeutic alternatives. The regulations were also intended to facilitate the availability, when
appropriate, of investigational new drugs for treatment use while protecting patient safety and

4

For the purpose of expanded access to investigational drugs for treatment use, immediately life-threatening disease
or condition means a stage of disease in which there is 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 selflimiting 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 (21 CFR 312.300(b)).
5

Federal Register of August 13, 2009 (74 FR 40900).

6

For information on the types of regulatory submissions that can be used to obtain expanded access, including
treatment INDs or treatment protocols, see the guidance for industry Expanded Access to Investigational Drugs for
Treatment Use — Questions and Answers. We update guidances periodically. To make sure you have the most
recent version of a guidance, check the FDA guidance web page at
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.

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avoiding interference with the development of investigational drugs for marketing under
approved applications.
The regulations describe criteria that must be met to authorize expanded access use, requirements
for expanded access submissions, and safeguards that are intended to protect patients and
preserve the ability to develop meaningful data about the safety and effectiveness of the drug
through clinical trials or drug development.
A.

Expanded Access for an Individual Patient

FDA may permit expanded access to an investigational new drug outside of a clinical
investigation, or to an approved drug where availability is limited by a REMS, for an
individual patient when the applicable criteria in § 312.305(a) (which apply to all types of
expanded access) and § 312.310(a) (which apply specifically to individual patient expanded
access, including for emergency use) are met.
Under the applicable criteria in § 312.305(a), FDA must determine that:
•

The patient to be treated has a serious or immediately life-threatening disease or
condition, and there is no comparable or satisfactory alternative therapy to diagnose,
monitor, or treat the disease or condition;

•

The potential patient benefit justifies the potential risks of the treatment use and those
potential risks are not unreasonable in the context of the disease or condition to be
treated; and

•

Providing the investigational drug 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.

Under the applicable criteria in § 312.310(a):
•

The patient’s physician must determine that the probable risk to the person from the
investigational drug is not greater than the probable risk from the disease or condition;
and

•

FDA must determine that the patient cannot obtain the investigational drug under another
IND or protocol.

For further information regarding those determinations, please see the guidance for industry
Expanded Access to Investigational Drugs for Treatment Use – Questions & Answers.7 In
7

For information on expanded access in general, including submitting an expanded access protocol to an existing
IND, see the guidance for industry Expanded Access to Investigational Drugs for Treatment Use — Questions and
Answers. In a separate guidance, Charging for Investigational Drugs under an IND — Questions and Answers,
FDA provides answers to questions concerning the regulations on charging for investigational drugs under an IND

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addition, § 312.305(b) of FDA’s expanded access regulations sets forth the submission
requirements for all types of expanded access requests. Section 312.310(b) contains additional
submission requirements for individual patient expanded access requests. A physician
submitting a request for individual patient expanded access may satisfy some of the submission
requirements by referring to information in an existing IND, ordinarily one held by the
investigational drug’s manufacturer, if the physician obtains permission from that IND holder
(e.g., the drug manufacturer or pharmaceutical company) (§ 312.305(b)(1)). If permission is
obtained, the physician should then provide to FDA a letter of authorization (LOA) from the
existing IND holder that permits FDA to reference that IND.
One of the requirements under § 312.305(b)(2) is that a “cover sheet” must be included “meeting
the requirements of § 312.23(a).” This provision applies to several types of submissions under
part 312, ranging from commercial INDs under § 312.23 that involve large groups of patients
enrolled in clinical trials to requests from physicians to use an investigational drug for an
individual patient. Form FDA 1571 (Investigational New Drug Application (IND)) is currently
used by sponsors for all types of IND submissions. However, FDA is concerned that physicians
requesting expanded access for an individual patient may have encountered difficulty in
completing Form FDA 1571 and providing the associated documents because Form FDA 1571 is
not tailored to requests for individual patient expanded access.
To streamline the submission process for individual patient expanded access INDs, FDA
developed Form FDA 3926, which is available for physicians to use to request expanded access
to an investigational drug outside of a clinical investigation, or to an approved drug where
availability is limited by a REMS, for an individual patient who has a serious or immediately
life-threatening disease or condition and there is no comparable or satisfactory alternative
therapy to diagnose, monitor, or treat the disease or condition. FDA generally intends to accept
submission of a completed Form FDA 3926 to comply with the IND submission requirements in
§§ 312.23, 312.305(b), and 312.310(b). FDA intends to consider a completed Form FDA 3926
with the box in Field 10.a. checked and the form signed by the physician to be a request in
accordance with § 312.10 for a waiver of any additional requirements in part 312 for an IND
submission, including additional information ordinarily provided in Form FDA 1571 and Form
FDA 1572 (Statement of Investigator, which provides the identity and qualifications of the
investigator conducting the clinical investigation). FDA concludes that such a waiver of any
additional requirements is appropriate for requests for individual patient expanded access INDs
because the physician’s noncompliance with any such requirements would not pose a significant
and unreasonable risk to the individual patient, and the physician’s compliance with any such
requirements is unnecessary for the Agency to evaluate the IND.
Form FDA 3926 may also be used for certain follow-up submissions to an individual patient
expanded access IND, which include the following: Initial Written IND Safety Report
(§ 312.32(c)); Follow-up to a Written IND Safety Report (§ 312.32(d)); Annual Report
(§ 312.33); Summary of Expanded Access Use (treatment completed) (§ 312.310(c)(2)); Change
in Treatment Plan (§ 312.30); General Correspondence or Response to FDA Request for
Information (§ 312.41); and Response to Clinical Hold (§ 312.42(e)).
(21 CFR 312.8). For additional information on expanded access, also see FDA’s website at
https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm.

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B.

Emergency Expanded Access for an Individual Patient

Under § 312.310(d), in an emergency situation that requires the patient to be treated before a
written submission can be made, the request to use the investigational drug for individual patient
expanded access may be made by telephone (or other rapid means of communication) to the
appropriate FDA review division. Authorization of the emergency use may be given by an FDA
official by telephone, provided the physician explains how the expanded access use will meet the
requirements of §§ 312.305 and 312.310 and agrees to submit an expanded access application
within 15 working days of FDA’s initial authorization of the expanded access use
(§ 312.310(d)(2)). The physician may choose to use Form FDA 3926 for the expanded access
application.

III.

CONSIDERATIONS AND REGULATORY REQUIREMENTS IN REQUESTING
EXPANDED ACCESS FOR AN INDIVIDUAL PATIENT

When a licensed physician would like to obtain an investigational drug outside of a clinical
investigation, or an approved drug where availability is limited by a REMS, for an individual
patient, the physician should first ensure that the investigational drug can be obtained. If so,
the physician should obtain an LOA from the entity that is the sponsor of the IND (e.g.,
commercial sponsor or drug manufacturer) being referenced. The LOA permits FDA to refer
to information that the sponsor of the IND has submitted to FDA (e.g., in a commercial IND).
In cases where it is not possible to obtain an LOA (e.g., the entity supplying the drug does not
have an IND filed with FDA), the physician should contact the relevant review division at
FDA to determine what information is needed to support the expanded access submission.
Physicians should also contact the review division if the individual patient expanded access
IND is for an approved drug where availability is limited by a REMS. The physician should
then submit an individual patient expanded access IND to the appropriate FDA review division
and may choose to use Form FDA 3926. Contact information for review divisions may be
found on FDA’s website at
https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/uc
m429610.htm.
Under individual patient expanded access INDs, the physician who submits an IND is
considered a sponsor-investigator (as defined in § 312.3) and is responsible for complying with
the responsibilities for both sponsors and investigators to the extent they are applicable to the
expanded access use, including submitting IND safety reports 8 and annual reports and
maintaining adequate drug disposition records. The responsibilities of sponsors and
investigators are described in subpart D of 21 CFR part 312 and in related guidance documents,
for example, in the guidance for industry Investigator Responsibilities—Protecting the Rights,
Safety, and Welfare of Study Subjects.

8

For additional information about FDA’s IND safety reporting requirements, please see the guidance for industry
and investigators Safety Reporting Requirements for INDs and BA/BE Studies.

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Contains Nonbinding Recommendations
The informed consent requirements in 21 CFR part 50 apply to treatment provided to patients
under expanded access INDs, and informed consent must be obtained before initiating
treatment, including in the case of emergency use, unless one of the exceptions found in part
50 applies. 9 Additionally, the institutional review board (IRB) requirements found in 21 CFR
part 56 apply (see § 312.305(c)(4)), and IRB approval must be obtained before starting
treatment under an expanded access IND unless it is for emergency use (in which case the IRB
must be notified of the emergency expanded access use within 5 working days of treatment
(§ 56.104(c)). 10 Upon request, FDA intends to allow for waivers of the requirement for review
and approval at a convened IRB meeting for individual patient expanded access INDs where
the IRB chairperson or another designated IRB member provides concurrence, as described in
the next paragraph.
For individual patient expanded access use of an investigational drug, FDA intends to consider
a completed Form FDA 3926 with the box in Field 10.b. checked and the form signed by the
physician to be a request for a waiver under § 56.105 of the requirements in § 56.108(c),
which relate to IRB review and approval at a convened IRB meeting at which a majority of the
members are present.11 FDA concludes that such a waiver is appropriate for individual patient
expanded access INDs when the physician obtains concurrence by the IRB chairperson or
another designated IRB member before treatment use begins.
Form FDA 3926 and accompanying instructions may be found on FDA’s website at
https://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm.

IV.

PROCEDURES AND TIMELINE FOR PROCESSING FORM FDA 3926

In a non-emergency situation, after receiving Form FDA 3926 (i.e., the IND), FDA will assign
an individual IND number to the IND and will either allow the treatment use to proceed or put
the application on clinical hold (see § 312.42). The IND will go into effect (i.e., treatment
9

For information on informed consent in general, see the draft guidance for IRBs, clinical investigators, and
sponsors Informed Consent Information Sheet. When final, this guidance will represent FDA’s current thinking
on this topic. For additional information on the part 50 informed consent exceptions, see the guidance for
institutional review boards, clinical investigators, and sponsors Exception from Informed Consent Requirements
for Emergency Research.
10

An IRB means any board, committee, or other group formally designated by an institution to review, to
approve the initiation of, and to conduct periodic review of biomedical research involving human subjects. The
primary purpose of IRB review is to assure that the rights and welfare of human subjects are protected, including
by determining that informed consent is obtained in accordance with and to the extent required by Federal
requirements. Institutions may have their own IRB to oversee human subjects research conducted within the
institution or by the staff of the institution. If the physician does not have access to a local IRB, an independent
IRB may be used. The Department of Health & Human Services’ Office for Human Research Protections
maintains a database of registered IRBs. Go to https://ohrp.cit.nih.gov/search/irbsearch.aspx?styp=bsc and click
on “Advanced Search.” Enter your state to find registered IRBs in your area.
11

Form FDA 1571 does not provide a field for requesting a waiver under § 56.105. However, a physician
submitting an individual patient expanded access IND using Form FDA 1571 may include a separate waiver
request with the application.

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with the investigational drug may proceed) after FDA notifies the physician or, if no
notification occurs, 30 days after FDA receives the completed Form FDA 3926. FDA
generally provides the sponsor with notification acknowledging the complete submission. If
the treatment use is not allowed to proceed, FDA generally will notify the physician of this
decision initially by telephone (or other rapid means of communication) and will follow up
with a written letter that details the reasons for FDA’s decision to place the IND on clinical
hold.
If there is an emergency and authorization of the expanded access use is requested before a
written submission can be made, the physician must explain how the expanded access use will
meet the criteria of §§ 312.305(a) and 312.310(a), as described previously in section II. In
these situations, FDA may authorize the expanded access use of the investigational drug, and
treatment may begin before FDA’s receipt of the written submission (including the LOA), but
the physician must agree to submit an expanded access submission within 15 working days of
FDA’s authorization of the expanded access use (§ 312.310(d)). When treatment involves the
emergency use of an investigational drug and approval from an IRB cannot be obtained before
treatment, treatment may begin without prior IRB approval provided the IRB is notified of the
emergency expanded access use within 5 working days of treatment (§ 56.104).
Secure email between FDA and sponsors is useful for informal communications when
confidential information may be included in the message (e.g., confidential patient information).
Parties who would like to establish secure email with FDA should email a request to
[email protected].

V.

PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the
Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995
(44 U.S.C. 3501-3520). The time required to complete this information collection is estimated
to average 45 minutes per response, including the time to review instructions, search existing
data sources, gather the data needed, and complete and review the information collection.
Send comments regarding this burden estimate or suggestions for reducing this burden to:
Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Avenue, Bldg. 51, rm. 6337, Silver Spring,
MD 20993-0002
This guidance also refers to previously approved collections of information found in FDA
regulations. The collections of information in 21 CFR part 312 have been approved under
OMB control number 0910-0014.
An Agency may not conduct or sponsor, and a person is not required to respond to, a collection
of information unless it displays a currently valid OMB control number. The OMB control
number for this information collection is 0910-0814 (expires 04/30/2019).

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