[Federal Register Volume 80, Number 27 (Tuesday, February 10, 2015)]
[Rules and Regulations]
[Pages 7318-7321]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-02561]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 312

[Docket No. FDA-2015-D-0268]


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Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of draft guidance.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing the availability of a draft guidance for industry entitled 
``Individual Patient Expanded Access Applications: Form FDA 3926.'' The 
draft guidance provides for public comment and describes draft Form FDA 
3926 (Individual Patient Expanded Access--Investigational New Drug 
Application (IND)), which, when finalized, FDA intends to make 
available for licensed physicians to use for expanded access requests 
for individual patient INDs. Individual patient expanded access allows 
for the use of an investigational drug outside of a clinical trial 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. When finalized, draft Form FDA 3926 is intended to provide a 
streamlined alternative for submitting an Investigational New Drug 
Application (IND) for use in cases of individual patient expanded 
access.

DATES: February 10, 2015. Although you can comment on any guidance at 
any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers 
your comment on this draft guidance before it begins work on the final 
version of the guidance, submit either electronic or written comments 
on the draft guidance by April 13, 2015. Submit either electronic or 
written comments concerning the collection of information proposed in 
the draft guidance by April 13, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10001 New 
Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 
20993, or to the Office of Communication, Outreach and Development, 
Center for Biologics Evaluation and Research (CBER), Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver 
Spring, MD 20993-0002. Send one self-addressed adhesive label to assist 
that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Lori Bickel, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6353, Silver Spring, MD 20993-0002, 301-
796-0210; or Stephen Ripley, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Individual Patient Expanded Access Applications: Form FDA 
3926.'' The draft guidance provides draft Form FDA 3926 for public 
comment. When finalized, draft Form FDA 3926 will be available for 
licensed physicians to use for expanded access requests for individual 
patient INDs as an alternative to Form FDA 1571 (Investigation New Drug 
Application (IND)).
    On August 13, 2009, FDA published a final rule (74 FR 40900, August 
13, 2009) to amend its IND regulations by removing the certain sections 
of part 312 (21 CFR part 312) on treatment use of investigational drugs 
and adding subpart I of part 312 on expanded access (part 312, subpart 
I).
    Subpart I describes the following categories of expanded access:

[[Page 7319]]

    <bullet> Expanded access for individual patients, including for 
emergency use;
    <bullet> Expanded access for intermediate-size patient populations 
(smaller than those typical of a treatment IND or treatment protocol); 
and
    <bullet> Expanded access through a treatment IND or treatment 
protocol (designed for use in larger patient populations).
    The final rule was, among other things, intended to increase 
awareness and knowledge of expanded access programs and the procedures 
for obtaining investigational drugs for treatment use for patients who 
have serious or immediately life-threatening diseases or conditions who 
lack therapeutic alternatives. The final rule was also intended to 
facilitate the availability, when appropriate, of investigational new 
drugs for treatment use, while protecting patient safety and avoiding 
interference with the development of investigational drugs for 
marketing under approved applications.
    The draft guidance is intended to address the submission of draft 
Form FDA 3926, when finalized, for a new individual patient expanded 
access IND by a licensed physician. For information on expanded access 
in general, including how to submit an expanded access protocol to an 
existing IND, see FDA's draft guidance for industry ``Expanded Access 
to Investigational Drugs for Treatment Use--Qs and As'' (available at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm).
    FDA may permit expanded access to an investigational new drug for 
an individual patient when the applicable criteria in Sec.  312.305(a), 
which pertains to all types of expanded access, and the criteria in 
Sec.  312.310(a), which pertains to individual patient expanded access, 
including in an emergency, are met. The physician may satisfy some of 
the submission requirements by referring to information in an existing 
IND, ordinarily the one held by the manufacturer, if the physician 
obtains permission from that IND holder. If permission is obtained, the 
physician should then provide FDA a letter of authorization (LOA) from 
the existing IND holder that permits FDA to reference that IND.
    Section 312.305(b) sets forth the submission requirements for all 
expanded access uses. One of the requirements under Sec.  312.305(b)(2) 
is that a ``cover sheet'' must be included ``meeting the requirements 
of Sec.  312.23(a).'' This provision applies to several types of 
submissions under part 312, ranging from commercial INDs under Sec.  
312.23 involving large groups of patients enrolled in clinical trials 
to requests from licensed physicians to use an investigational drug for 
an individual patient. FDA is concerned that its goal of facilitating 
access to drugs for individual patient treatment use may have been 
complicated by difficulties experienced by physicians in submitting 
Form FDA 1571 (currently used by sponsors for all types of IND 
submissions) including associated documents, which is not tailored to 
requests for individual patient expanded access.
    In an effort to streamline the submission process for individual 
patient expanded access INDs, FDA intends to make draft Form FDA 3926 
available, when finalized, for licensed physicians to request expanded 
access to an investigational drug outside of a clinical trial for an 
individual patient who has a serious or immediately life-threatening 
disease or condition and for whom there is no comparable or 
satisfactory alternative therapy to diagnose, monitor, or treat the 
disease or condition (i.e., for individual patient expanded access, 
including in emergencies). Draft Form FDA 3926 is shorter than Form FDA 
1571 and requests the following information: (1) Patient's initials and 
date of submission; (2) clinical information; (3) treatment 
information; (4) LOA from the investigational drug's manufacturer, if 
applicable; (5) physician's qualifications; (6) physician's contact 
information and the physician's IND number, which is not the same as 
the manufacturer's IND number, (if the number is known); (7) request 
for authorization to use draft Form FDA 3926, when finalized, for 
individual patient expanded access applications instead of Form FDA 
1571; and (8) certification statement and physician's signature. Draft 
Form FDA 3926 is provided in the draft guidance for public comment as 
Appendix 1.
    As discussed in the draft guidance, FDA intends to accept 
submission of draft Form FDA 3926, when finalized, to comply with the 
IND submission requirements in Sec. Sec.  312.23, 312.305(b), and 
312.310(b). To the extent that information required under part 312 is 
not contained in draft Form FDA 3926, FDA intends to consider the 
submission of that form, when finalized, with the box in item 7 checked 
and the form signed by the physician, to constitute a request under 
Sec.  312.10 to waive any other applicable application requirements, 
including additional information included in Form FDA 1571 and Form FDA 
1572 (Statement of Investigator, providing the identity and 
qualifications of the investigator conducting the clinical 
investigation).
    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, and authorization of the emergency use may be 
given by the FDA official over the telephone, provided the physician 
explains how the expanded access use will meet the requirements of 
Sec. Sec.  312.305 and 312.310 and agrees to submit an expanded access 
submission within 15 working days of FDA's initial authorization of the 
expanded access use (Sec.  312.310(d)).
    The draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on the use of 
draft Form FDA 3926, when finalized, by licensed physicians for 
individual patient expanded access applications. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    The draft 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 
title, description, and respondent description of the information 
collection are given under this section with an estimate of the annual 
reporting burden. Included in the estimate is the time for reviewing 
instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing the 
collection of information.
    We invite comments on these topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques,

[[Page 7320]]

when appropriate, and other forms of information technology.
    Title: Draft Guidance on Individual Patient Expanded Access 
Applications: Form FDA 3926.
    Description: The draft guidance provides for public comment and 
describes draft Form FDA 3926. When finalized, draft Form FDA 3926 will 
be available for licensed physicians to request the use of an 
investigational drug outside of a clinical trial 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 (i.e., 
for individual patient expanded access). FDA regulations (Sec.  
312.305(b)(2)) require that a cover sheet meeting the requirements of 
Sec.  312.23(a) (currently Form FDA 1571) be submitted for all expanded 
access requests.
    As explained in the draft guidance, the following information would 
be submitted to FDA by those using draft Form FDA 3926 when it is 
finalized:
    <bullet> Patient's initials and date of submission.
    <bullet> Clinical information, including indication, brief clinical 
history of the patient (age, gender, weight, allergies, diagnosis, 
prior therapy, response to prior therapy), and the rationale for 
requesting the proposed treatment, including an explanation of why the 
patient lacks other therapeutic options.
    <bullet> Treatment information, including the investigational 
drug's name and manufacturer and the treatment plan. The plan should 
include the planned dose, route of administration, planned duration of 
treatment, monitoring procedures, and planned modifications to the 
treatment plan in the event of toxicity.
    <bullet> LOA obtained from the investigational drug's manufacturer 
and attached to draft Form FDA 3926, if applicable.
    <bullet> Physician's qualification statement that specifies the 
medical school attended, year of graduation, medical specialty, state 
medical license number, current employment, and job title. 
Alternatively, the first few pages of the physician's curriculum vitae 
may be attached, provided they include the information described 
previously.
    <bullet> Physician's contact information, including the physical 
address, email address, telephone number, facsimile number, and 
physician's IND number, if known.
    <bullet> Request for authorization to use Form FDA 3926, when 
finalized, for the initial submission of individual patient expanded 
access applications instead of Form FDA 1571.
    <bullet> Signature of the physician certifying that treatment will 
not begin until 30 days after FDA receives the application, unless the 
submitting physician receives earlier notification from FDA that the 
treatment may proceed; that the physician will obtain informed consent, 
consistent with Federal requirements; that an institutional review 
board (IRB) that complies with the Federal IRB requirements will be 
responsible for initial and continuing review and approval of the 
treatment use; and that in the case of an emergency request, treatment 
may begin without prior IRB approval, provided that the IRB is notified 
of the emergency treatment within 5 working days of treatment.
    Section 312.305(b)(2) of FDA's expanded access regulations sets 
forth the submission requirements for all types of expanded access 
requests for investigational drugs. Section 312.310(b) contains 
additional submission requirements for individual patient expanded 
access requests, and Sec.  312.310(d) contains the requirements for 
requesting individual patient expanded access for emergency use. FDA 
currently has OMB approval under control number 0910-0014 for 
individual patient expanded access information collection under 
Sec. Sec.  312.305(b), 312.310(b), and 312.310(d). As shown in Table 1, 
based on data for the number of these responses to FDA during 2011, 
2012, and 2013, we estimate that we will receive approximately 593 
requests annually for individual patient expanded access use from 
approximately 393 licensed physicians and will receive approximately 
560 requests annually for individual patient expanded access emergency 
use from approximately 397 licensed physicians.
    The current OMB approval also estimates that it takes each licensed 
physician approximately 8 hours to request each individual patient 
expanded access use and approximately 16 hours to request each 
individual patient expanded access for emergency use. These estimates 
are based on the use of Form FDA 1571. When a finalized Form FDA 3926 
is submitted instead of current Form FDA 1571, we estimate that the 
burden time will be 45 minutes, resulting in a burden reduction of 7 
hours and 15 minutes for each individual patient expanded access 
request and a burden reduction of 15 hours and 15 minutes for each 
individual patient expanded access for emergency use request. That 
estimate is based on information provided by Department of Health and 
Human Services (DHHS) personnel who are familiar with preparing and 
reviewing expanded access submissions by practicing physicians. As 
shown in Table 1, we estimate a total of approximately 864.75 hours 
annually for requesting individual patient expanded access use and 
individual patient expanded access emergency use using draft Form FDA 
3926, when finalized. This is a reduction of 16,727.25 hours from what 
was approved under OMB control number 0910-0014 for these submissions.
    The total estimated reporting burden for the draft guidance is as 
follows:

                                                       Table 1--Estimated Annual Reporting Burden
                               [Reduces currently approved burden of 17,592 hours under 0910-0014 by 16,727.25 hours] \1\
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                                                                                         Number of                      Average  burden
Draft guidance on individual patient expanded  access applications;     Number of      responses per     Total annual    per  response     Total hours
                           Form FDA 3926                               respondents       respondent       responses        (minutes)
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Expanded access submission for treatment of an individual patient,              790             1.46            1,153               45           864.75
 including submission of draft Form FDA 3926, when finalized,
 instead of Form FDA 1571..........................................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


[[Page 7321]]

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; or http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; or 
http://www.regulations.gov.

    Dated: February 3, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-02561 Filed 2-9-15; 8:45 am]
BILLING CODE 4164-01-P