Individual Patient Expanded Access Applications: Form FDA 3926; Draft Guidance for Industry; Availability, 7318-7321 [2015-02561]
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Definitions.
10. Appendix to Part 163 is amended
by adding a listing under section IV in
numerical order to read as follows:
PART 178—APPROVAL OF
INFORMATION COLLECTION
REQUIREMENTS
Appendix to Part 163—Interim (a)(1)(A)
List
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(ix) The maintenance of any
documentation that the importer may
have in support of a claim for
preferential tariff treatment under the
United States-Australia Free Trade
Agreement (AFTA), including an AFTA
importer’s supporting statement.
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Authority: 5 U.S.C. 301; 19 U.S.C. 1624; 44
U.S.C. 3501 et seq.
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§ 10.723–10.727 AFTA records that the
importer may have in support of an AFTA
claim for preferential tariff treatment,
including an importer’s supporting
statement.
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11. The authority citation for part 178
continues to read as follows:
12. Section 178.2 is amended by
adding new listings for ‘‘§§ 10.723 and
10.724’’ to the table in numerical order
to read as follows:
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§ 178.2
Listing of OMB control numbers.
19 CFR Section
Description
OMB control
No.
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[FR Doc. 2015–02720 Filed 2–9–15; 8:45 am]
BILLING CODE 9111–14–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
21 CFR Part 312
[Docket No. FDA–2015–D–0268]
Individual Patient Expanded Access
Applications: Form FDA 3926; Draft
Guidance for Industry; Availability
Food and Drug Administration,
HHS.
Notice of draft guidance.
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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single copies of the draft guidance to the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access to the draft guidance document.
ADDRESSES:
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
SUMMARY:
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.
DATES:
Food and Drug Administration
ACTION:
*
a clinical trial for an individual patient
who has a serious or immediately lifethreatening 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.
*
R. Gil Kerlikowske,
Commissioner.
Approved: February 5, 2015.
Timothy E. Skud,
Deputy Assistant Secretary of the Treasury.
AGENCY:
*
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*
*
Submit electronic comments on the
draft guidance to https://
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:
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Federal Register / Vol. 80, No. 27 / Tuesday, February 10, 2015 / Rules and Regulations
• Expanded access for individual
patients, including for emergency use;
• Expanded access for intermediatesize patient populations (smaller than
those typical of a treatment IND or
treatment protocol); and
• 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 https://www.fda.gov/Drugs/
GuidanceComplianceRegulatory
Information/Guidances/default.htm).
FDA may permit expanded access to
an investigational new drug for an
individual patient when the applicable
criteria in § 312.305(a), which pertains
to all types of expanded access, and the
criteria in § 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 § 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 involving large groups of
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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 lifethreatening 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 §§ 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 § 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
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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
§§ 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 (§ 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,
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Federal Register / Vol. 80, No. 27 / Tuesday, February 10, 2015 / Rules and Regulations
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
(§ 312.305(b)(2)) require that a cover
sheet meeting the requirements of
§ 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:
• Patient’s initials and date of
submission.
• 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.
• 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.
• LOA obtained from the
investigational drug’s manufacturer and
attached to draft Form FDA 3926, if
applicable.
• 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.
• Physician’s contact information,
including the physical address, email
address, telephone number, facsimile
number, and physician’s IND number, if
known.
• 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.
• 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
§ 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
§§ 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
rljohnson on DSK3VPTVN1PROD with RULES
Draft guidance on individual patient expanded
access applications; Form FDA 3926
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average
burden per
response
(minutes)
Total hours
Expanded access submission for treatment of an individual patient, including submission of draft Form FDA
3926, when finalized, instead of Form FDA 1571 ...........
790
1.46
1,153
45
864.75
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
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Federal Register / Vol. 80, No. 27 / Tuesday, February 10, 2015 / Rules and Regulations
III. Comments
Interested persons may submit either
electronic comments regarding this
document to https://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 https://
www.regulations.gov.
IV. Electronic Access
Persons with access to the Internet
may obtain the document at https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm; or https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/Guidances/default.htm; or
https://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
DEPARTMENT OF STATE
22 CFR Part 96
[Public Notice: 9023]
RIN 1400–AD45
Adoptions: Regulatory Change To
Clarify the Application of the
Accreditation Requirement and
Standards in Cases Covered by the
Intercountry Adoption Universal
Accreditation Act
Department of State.
Final rule.
AGENCY:
ACTION:
This rule amends the
Department of State (Department)
interim rule on the accreditation and
approval of adoption service providers
in intercountry adoptions, and adopts
the interim rule as final. The revisions
reflect the requirement of the
Intercountry Adoption Universal
Accreditation Act of 2012 (UAA) that
the accreditation standards developed
in accordance with the 1993 Hague
Convention on Protection of Children
and Co-operation in Respect of
Intercountry Adoption (Convention) and
the Intercountry Adoption Act of 2000
(IAA), which previously only applied in
Convention adoption cases, apply also
in non-Convention adoption cases. Non-
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SUMMARY:
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convention adoption cases are known as
‘‘orphan’’ cases, defined in the
Immigration and Nationality Act (INA).
This rule also revises the accreditation
rule by referring to the Department of
Homeland Security (DHS) Convention
home study regulation and deleting
obsolete references, such as any
reference to temporary accreditation.
DATES: This document finalizes the
interim final rule published on July 14,
2014 (79 FR 40629), and is effective
February 10, 2015.
FOR FURTHER INFORMATION CONTACT:
Office of Legal Affairs, Overseas Citizen
Services, U.S. Department of State, CA/
OCS/L, SA–17, Floor 10, Washington,
DC 20522–1710; (202) 485–6079.
SUPPLEMENTARY INFORMATION:
Why is the Department promulgating
this rule?
This rule clarifies that under the
Intercountry Adoption Universal
Accreditation Act of 2012 (UAA), signed
into law January 14, 2013, and effective
July 14, 2014, the accreditation
requirement and standards found in 22
CFR part 96 apply to any person
(including non-profit agencies, for-profit
agencies and individuals but excluding
government agencies and tribal
authorities), providing adoption services
on behalf of prospective adoptive
parents in an ‘‘orphan’’ intercountry
adoption case described under section
101(b)(1)(F) of the Immigration and
Nationality Act. Specifically, under
Section 2 of the UAA ‘‘[t]he provisions
of title II and section 404 of the
Intercountry Adoption Act of 2000 (42
U.S.C. 14901 et seq.), and related
implementing regulations, shall apply to
any person offering or providing
adoption services in connection with a
child described in section 101(b)(1)(F)
of the Immigration and Nationality Act
(8 U.S.C. 1101(b)(1)(F)), to the same
extent as they apply to the offering or
provision of adoption services in
connection with a Convention
adoption.’’
Title II of the Intercountry Adoption
Act of 2000 (IAA) (Pub. L. 106–279)
requires that any person providing
adoption services in a Convention case
be an accredited, approved, or an
exempted adoption service provider,
and section 404 imposes civil and
criminal penalties for violations of the
Act. On February 15, 2006 the
Department of State published
implementing regulations at 71 FR 8064,
on the accreditation and approval of
agencies and persons in accordance
with the Convention and the IAA.
The UAA extends that rule from
Convention cases to ‘‘orphan’’ cases.
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7321
This regulatory change includes a
number of technical edits to facilitate
interpretation of the regulatory
requirements and clarify designated
accrediting entities’ authority under the
UAA and the IAA.
The Department is amending the
regulation to make 22 CFR part 96, as
affected by the UAA, easier to read. This
rule will aid the accrediting entity
applying the standards and adoption
service providers required to comply
with the standards. In particular, this
rule adds references to the UAA where
the IAA is referenced; adds a sentence
concerning the UAA effective date;
redefines ‘‘Central Authority’’ to include
competent authorities, thereby
clarifying how the term applies in
countries that are not party to the
Convention; redefines adoption records
to include non-Convention case records
and changes Section 96.25(b)
concerning accrediting entity access to
non-Convention records in cases subject
to the UAA; defines the terms INA, IAA,
and intercountry adoption; refers to
‘‘accreditation and approval’’ instead of
to ‘‘Convention accreditation and
approval;’’ revises § 96.46(a)(4) to clarify
that foreign supervised providers in
non-Convention countries may not have
a pattern of licensing suspensions
relating to key Convention principles;
and revises references to ‘‘Convention
adoption,’’ ‘‘cases subject to the
Convention,’’ ‘‘Convention case,’’
‘‘Convention country,’’ and
‘‘Convention-related activity’’ to ensure
that such references include nonConvention adoptions, activities,
countries, and cases under the UAA.
Additionally, this rule corrects the
references in 22 CFR 96.37(f)(2), and
96.47(a)(4) and (b), to refer to the correct
Department of Homeland Security
(DHS) definition of home study preparer
and home study requirements. When
the original rule was issued in 2006,
DHS had not yet published its final rule
concerning home studies in Convention
cases. Thus, the 2006 State Department
rule referred to the ‘‘orphan’’ home
study requirements under 8 CFR
204.3(b) and (e), instead of the
Convention home study requirements
found in 8 CFR 204.301 and 311. This
rule references the correct DHS
regulation. The change clarifies that the
home study must be prepared by an
accredited agency, approved person,
exempted provider, or a supervised
provider. In addition, when the home
study is not performed in the first
instance by an accredited agency, then
an accredited agency must review and
approve it. The orphan and Convention
home study requirements also differ
concerning the required elements,
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]]>Agencies
[Federal Register Volume 80, Number 27 (Tuesday, February 10, 2015)]
[Rules and Regulations]
[Pages 7318-7321]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-02561]
=======================================================================
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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 https://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]]
Expanded access for individual patients, including for
emergency use;
Expanded access for intermediate-size patient populations
(smaller than those typical of a treatment IND or treatment protocol);
and
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
https://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:
Patient's initials and date of submission.
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.
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.
LOA obtained from the investigational drug's manufacturer
and attached to draft Form FDA 3926, if applicable.
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.
Physician's contact information, including the physical
address, email address, telephone number, facsimile number, and
physician's IND number, if known.
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.
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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
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)
--------------------------------------------------------------------------------------------------------------------------------------------------------
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..........................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 https://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 https://www.regulations.gov.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; or https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm; or
https://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
