Agency Information Collection Activities: Proposed Collection; Comment Request; Investigational New Drug Regulations, 4914-4917 [2011-1758]
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Federal Register / Vol. 76, No. 18 / Thursday, January 27, 2011 / Notices
FDA based these estimates on the
number of inquiries that have been
received concerning the program and
the number of requests for application
forms over the past 3 years.
Dated: January 19, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–1760 Filed 1–26–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–N–0042]
Agency Information Collection
Activities: Proposed Collection;
Comment Request; Investigational
New Drug Regulations
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing an
opportunity for public comment on the
proposed collection of certain
information by the Agency. Under the
Paperwork Reduction Act of 1995 (the
PRA), Federal Agencies are required to
publish notice in the Federal Register
concerning each proposed collection of
information, including each proposed
extension of an existing collection of
information, and to allow 60 days for
public comment in response to the
notice. This notice solicits comments on
requirements under which the clinical
investigation of the safety and
effectiveness of unapproved new drugs
and biological products can be
conducted.
DATES: Submit either electronic or
written comments on the collection of
information by March 28, 2011.
ADDRESSES: Submit electronic
comments on the collection of
information to: https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT:
Elizabeth Berbakos, Office of
Information Management, Food and
Drug Administration, 1350 Piccard Dr.,
P150–400B, Rockville, MD 20850. 301–
796–3792.
Elizabeth.Berbakos@fda.hhs.gov.
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SUMMARY:
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Under the
PRA (44 U.S.C. 3501–3520), Federal
Agencies must obtain approval from the
Office of Management and Budget
(OMB) for each collection of
information they conduct or sponsor.
‘‘Collection of information’’ is defined in
44 U.S.C. 3502(3) and 5 CFR 1320.3(c)
and includes Agency requests or
requirements that members of the public
submit reports, keep records, or provide
information to a third party. Section
3506(c)(2)(A) of the PRA (44 U.S.C.
3506(c)(2)(A)) requires Federal Agencies
to provide a 60-day notice in the
Federal Register concerning each
proposed collection of information,
including each proposed extension of an
existing collection of information,
before submitting the collection to OMB
for approval. To comply with this
requirement, FDA is publishing notice
of the proposed collection of
information set forth in this document.
With respect to the following
collection of information, FDA invites
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,
when appropriate, and other forms of
information technology.
SUPPLEMENTARY INFORMATION:
Investigational New Drug (IND)
Regulations—21 CFR Part 312 (OMB
Control Number 0910–0014)—Extension
FDA is requesting OMB approval for
the reporting and recordkeeping
requirements contained in the FDA
regulations ‘‘Investigational New Drug
Application’’ in part 312 (21 CFR part
312). Part 312 implements provisions of
section 505(i) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 355(i)) (the
FD&C Act) to issue regulations under
which the clinical investigation of the
safety and effectiveness of unapproved
new drugs and biological products can
be conducted.
FDA is charged with implementing
statutory requirements that drug
products marketed in the United States
be shown to be safe and effective,
properly manufactured, and properly
labeled for their intended uses. Section
505(a) of the act provides that a new
drug may not be introduced or delivered
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for introduction into interstate
commerce in the United States unless
FDA has previously approved a new
drug application (NDA). FDA approves
an NDA only if the sponsor of the
application first demonstrates that the
drug is safe and effective for the
conditions prescribed, recommended, or
suggested in the product’s labeling.
Proof must consist, in part, of adequate
and well-controlled studies, including
studies in humans, that are conducted
by qualified experts. The IND
regulations establish reporting
requirements that include an initial
application as well as amendments to
that application, reports on significant
revisions of clinical investigation plans,
and information on a drug’s safety or
effectiveness. In addition, the sponsor is
required to give FDA an annual
summary of the previous year’s clinical
experience. Submissions are reviewed
by medical officers and other agency
scientific reviewers assigned
responsibility for overseeing the specific
study. The IND regulations also contain
recordkeeping requirements that pertain
to the responsibilities of sponsors and
investigators. The detail and complexity
of these requirements are dictated by the
scientific procedures and human subject
safeguards that must be followed in the
clinical tests of investigational new
drugs.
The IND information collection
requirements provide the means by
which FDA can do the following: (1)
Monitor the safety of ongoing clinical
investigations; (2) determine whether
the clinical testing of a drug should be
authorized; (3) ensure production of
reliable data on the metabolism and
pharmacological action of the drug in
humans; (4) obtain timely information
on adverse reactions to the drug; (5)
obtain information on side effects
associated with increasing doses; (6)
obtain information on the drug’s
effectiveness; (7) ensure the design of
well-controlled, scientifically valid
studies; (8) obtain other information
pertinent to determining whether
clinical testing should be continued and
information related to the protection of
human subjects. Without the
information provided by industry in
response to the IND regulations, FDA
cannot authorize or monitor the clinical
investigations which must be conducted
prior to authorizing the sale and general
use of new drugs. These reports enable
FDA to monitor a study’s progress, to
assure subject safety, to assure that a
study will be conducted ethically, and
to increase the likelihood that the
sponsor will conduct studies that will
be useful in determining whether the
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drug should be marketed and available
for use in medical practice.
There are two forms that are required
under part 312:
Form FDA–1571—‘‘Investigational
New Drug Application’’—A person who
intends to conduct a clinical
investigation submits this form to FDA.
It includes the following information:
(1) A cover sheet containing background
information on the sponsor and
investigator, (2) a table of contents, (3)
an introductory statement and general
investigational plan, (4) an investigator’s
brochure describing the drug substance,
(5) a protocol for each planned study,
(6) chemistry, manufacturing, and
control information for each
investigation, (7) pharmacology and
toxicology information for each
investigation, and (8) previous human
experience with the investigational
drug.
Form FDA–1572—‘‘Investigator
Statement’’—Before permitting an
investigator to begin participation in an
investigation, the sponsor must obtain
and record this form. It includes
background information on the
investigator and the investigation, and a
general outline of the planned
investigation and the study protocol.
FDA is requesting OMB approval for
the following reporting and
recordkeeping requirements in part 312:
Reporting Requirements
21 CFR 312.2(e)—Requests for FDA advice on
the applicability of part 312 to a planned
clinical investigation.
21 CFR 312.8—Charging for investigational
drugs under an IND.
21 CFR 312.10—Applications for waiver of
requirements under part 312. As
indicated in § 312.10(a), estimates for
this requirement are included under
§§ 312.23 and 312.31. In addition,
separate requests under § 312.10 are
estimated in table 1 of this document.
21 CFR 312.20(c)—Applications for
investigations involving an exception
from informed consent under § 50.24 (21
CFR 50.24). Estimates for this
requirement are included under § 312.23.
21 CFR 312.23—INDs (content and format).
21 CFR 312.23(a)(1)—Cover sheet FDA–1571.
21 CFR 312.23(a)(2) —Table of Contents.
21 CFR 312.23(a)(3)—Investigational plan for
each planned study.
21 CFR 312.23(a)(5)—Investigator’s brochure.
21 CFR 312.23(a)(6)—Protocols—Phase 1, 2,
and 3.
21 CFR 312.23(a)(7)—Chemistry,
manufacturing, and control information.
21 CFR 312.23(a)(7)(iv)(a),(b),(c)—A
description of the drug substance, a list
of all components, and any placebo used.
21 CFR 312.23(a)(7)(iv)(d)—Labeling: Copies
of labels and labeling to be provided
each investigator.
21 CFR 312.23(a)(7)(iv)(e)—Environmental
impact analysis regarding drug
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manufacturing and use.
21 CFR 312.23(a)(8)—Pharmacological and
toxicology information.
21 CFR 312.23(a)(9)—Previous human
experience with the investigational drug.
21 CFR 312.23(a)(10)—Additional
information.
21 CFR 312.23(a)(11)—Relevant information.
21 CFR 312.23(f)—Identification of exception
from informed consent.
21 CFR 312.30—Protocol amendments.
21 CFR 312.30(a)—New protocol.
21 CFR 312.30(b)—Change in protocol.
21 CFR 312.30(c)—New investigator.
21 CFR 312.30(d)—Content and format.
21CFR 312.30(e)—Frequency.
21 CFR 312.31—Information amendments.
21CFR 312.31(b)—Content and format.
—Chemistry, toxicology, or technical
information.
21 CFR 312.32—Safety reports.
21 CFR 312.32(c)(1)—Written reports to FDA
and to investigators.
21 CFR 312.32(c)(2)—Telephone reports to
FDA for fatal or life-threatening
experience.
21 CFR 312.32(c)(3)—Format or frequency.
21 CFR 312.32(d)—Follow up submissions.
21 CFR 312.33—Annual reports.
21 CFR 312.33(a)—Individual study
information.
21 CFR 312.33(b)—Summary information.
21 CFR 312.33(b)(1)—Adverse experiences.
21 CFR 312.33(b)(2)—Safety report summary.
21 CFR 312.33(b)(3)—List of fatalities and
causes of death.
21 CFR 312.33(b)(4)—List of discontinuing
subjects.
21 CFR 312.33(b)(5)—Drug action.
21 CFR 312.33(b)(6)—Preclinical studies and
findings.
21 CFR 312.33(b)(7)—Significant changes.
21 CFR 312.33(c)—Next year general
investigational plan.
21 CFR 312.33(d)—Brochure revision.
21 CFR.312.33(e)—Phase I protocol
modifications.
21 CFR.312.33(f)—Foreign marketing
developments.
21 CFR 312.38(b) and (c)—Notification of
withdrawal of an IND.
21 CFR 312.42(e)—Sponsor requests that a
clinical hold be removed and submits a
complete response to the issues
identified in the clinical hold order.
21 CFR 312.44(c) and (d)—Opportunity for
sponsor response to FDA when IND is
terminated.
21 CFR 312.45(a) and (b)—Sponsor request
for, or response to, inactive status
determination of an IND.
21 CFR 312.47(b)—‘‘End-of-Phase 2’’ meetings
and ‘‘Pre-NDA’’ meetings.
21 CFR 312.53(c)—Investigator information.
Investigator report (Form FDA–1572) and
narrative; investigator’s background
information; Phase 1 outline of planned
investigation and Phase 2 outline of
study protocol.
21 CFR 312.54(a) and (b)—Sponsor
submissions concerning investigations
involving an exception from informed
consent under § 50.24.
21 CFR 312.55(b)—Sponsor reports to
investigators on new observations,
especially adverse reactions and safe use.
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4915
Only ‘‘new observations’’ are estimated
under this section; investigator
brochures are included under § 312.23.
21 CFR 312.56(b),(c), and (d)—Sponsor
monitoring of all clinical investigations,
investigators, and drug safety;
notification to FDA.
21 CFR 312.58(a)—Sponsor’s submission of
records to FDA on request.
21 CFR 312.64—Investigator reports to the
sponsor.
21 CFR 312.64(a)—Progress reports.
21 CFR 312.64(b)—Safety reports.
21 CFR 312.64(c)—Final reports.
21 CFR 312.66—Investigator reports to
Institutional Review Board. Estimates for
this requirement are included under
§ 312.53.
21 CFR 312.70(a)—Investigator
disqualification; opportunity to respond
to FDA.
21 CFR 312.83—Sponsor submission of
treatment protocol. Estimates for this
requirement are included under
§ 312.320.
21 CFR 312.85—Sponsors conducting Phase
4 studies. Estimates for this requirement
are included under § 312.23 in 0910–
0014, and §§ 314.50, 314.70, and 314.81
in 0910–0001.
21 CFR 312.110(b)—Request to export an
investigational drug.
21 CFR 312.120—Submissions related to
foreign clinical studies not conducted
under an IND.
21 CFR 312.130(d)—Request for disclosable
information for investigations involving
an exception from informed consent
under § 50.24.
21 CFR 312.310(b); 312.305(b)—Submissions
related to expanded access and treatment
of an individual patient.
21 CFR 312.310(d)—Submissions related to
emergency use of an investigational new
drug.
21 CFR 312.315(c); 312.305(b)—Submissions
related to expanded access and treatment
of an intermediate size patient
population.
21 CFR 312.320—Submissions related to
treatment IND or treatment protocol.
Recordkeeping Requirements
21 CFR 312.52(a)—Transfer of obligations to
a contract research organization.
21 CFR 312.57—Sponsor recordkeeping.
21 CFR 312.59—Sponsor recordkeeping of
disposition of unused supply of drugs.
Estimates for this requirement are
included under § 312.57.
21 CFR 312.62(a)—Investigator
recordkeeping of disposition of drugs.
21 CFR 312.62(b)—Investigator
recordkeeping of case histories of
individuals.
21 CFR 312.120(d)—Recordkeeping
requirements for submissions related to
foreign clinical studies not conducted
under an IND. Estimates for this
requirement are included under § 312.57.
21 CFR 312.160(a)(3)—Records maintenance:
shipment of drugs for investigational use
in laboratory research animals or in vitro
tests.
21 CFR 312.160(c)—Shipper records of
alternative disposition of unused drugs.
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Federal Register / Vol. 76, No. 18 / Thursday, January 27, 2011 / Notices
In the tables in this document, the
estimates for ‘‘No. of Respondents,’’
‘‘Annual Frequency per Response,’’ and
‘‘Total Annual Responses’’ were
obtained from the Center for Drug
Evaluation and Research (CDER) and the
Center for Biologics Evaluation and
Research (CBER) reports and data
management systems for submissions
received in 2007 and from other sources
familiar with the number of submissions
received under part 312. The estimates
for ‘‘Hours per Response’’ were made by
CDER and CBER individuals familiar
with the burden associated with these
reports and from estimates received
from the pharmaceutical industry.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN FOR HUMAN DRUGS 1
21 CFR section
No. of respondents
Annual frequency
per response
Total annual
responses
Hours per
response
Total hours
312.2(e) ......................................
312.8 ..........................................
312.10 ........................................
312.23(a) through (f) ..................
312.30(a) through (e) .................
312.31 (b) ...................................
312.32(c) and (d) .......................
312.33(a) through (f) ..................
312.38(b) and (c) .......................
312.42(e) ....................................
312.44(c) and (d) .......................
312.45(a) and (b) .......................
312.47(b) ....................................
312.53(c) ....................................
312.54(a) and (b) .......................
312.55(b) ....................................
312.56(b), (c), and (d) ................
312.58(a) ....................................
312.64 ........................................
312.70(a) ....................................
312.110(b) ..................................
312.120 ......................................
312.130(d) ..................................
312.310(b) and 312.305(b) ........
312.310(d) ..................................
312.315(c) and 312.305(b) ........
312.320 ......................................
455
30
4
2,496
2,030
153
985
2,564
654
149
44
254
281
21,194
0
985
18
91
31,791
4
23
115
3
988
525
68
9
1.03
1.13
1
1.26
8.91
2.97
23.06
2.34
1.34
1.10
1
1.43
1.8
1
0
2,306
1
4.10
1
1
18.26
5
1
1
1.23
1
1.11
469
34
4
3,145
18,087
454
22,714
6,000
876
164
44
363
506
21,194
0
2,271,410
18
373
31,791
4
420
575
3
988
646
68
10
24
48
10
1,600
284
100
32
360
28
284
16
12
160
80
48
48
80
8
24
40
75
32
8
8
16
120
300
11,256
1,632
40
5,032,000
5,136,708
45,400
726,848
2,160,000
24,528
46,576
704
4,356
80,960
1,695,520
0
109,027,680
1,440
2,984
762,984
160
31,500
18,400
24
7,904
10,336
8,160
3,000
Total ....................................
................................
..................................
................................
................................
124,841,100
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR HUMAN DRUGS 1
Number of
recordkeepers
21 CFR Section
Annual frequency
per recordkeeping
Total annual
records
Hours per record
Total hours
312.52(a) ..................................
312.57 ......................................
312.62(a) ..................................
312.62(b) ..................................
312.160(a)(3) ...........................
312.160(c) ................................
335
75
14,732
147,320
547
547
1.5
485.28
1
1
1.4
1.4
503
36,396
14,732
147,320
766
766
2
100
40
40
.5
.5
1,006
3,639,600
589,280
5,892,800
383
383
Total ..................................
................................
..................................
................................
..................................
10,123,452
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN FOR BIOLOGICS 1
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21 CFR Section
No. of respondents
312.7(d) ......................................
312.23(a) through (f) and
312.120(b), (c)(2), and (c)(3)
312.30(a) through (e) .................
312.31(b) ....................................
312.32(c) and (d) and 312.56(c)
312.33(a) through (f) and
312.56(c) ................................
312.35(a) and (b) .......................
312.36 ........................................
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Annual frequency
per response
Total annual
responses
Hours per response
Total hours
41
1.4
57
24
1,368
433
590
263
294
1.3
6.8
29.3
13.7
563
4,012
7,706
4,028
1,808
284
100
32
1,017,904
1,139,408
770,600
128,896
647
1
6
2.3
1
1
1,488
1
6
360
300
16
535,680
300
96
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Federal Register / Vol. 76, No. 18 / Thursday, January 27, 2011 / Notices
TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN FOR BIOLOGICS 1—Continued
21 CFR Section
No. of respondents
Annual frequency
per response
Total annual
responses
Hours per response
Total hours
312.38(b) and (c) .......................
312.42(e) ....................................
312.44(c) and (d) .......................
312.45(a) and (b) .......................
312.47(b) ....................................
312.53(c) ....................................
312.54(a) and (b) .......................
312.55(b) ....................................
312.56(b) and (d) .......................
312.58(a) ....................................
312.64(a) through (d) .................
312.70(a) ....................................
312.110(b) ..................................
312.130(d) ..................................
117
74
17
60
43
348
1
138
14
8
6,003
6
21
1
1.3
1.5
1.1
1.8
1.5
6.6
1
2.5
1.6
1
3.5
1
1
1
152
111
19
108
65
2,297
1
345
22
8
21,010
6
21
1
28
284
16
12
160
80
48
48
80
8
24
40
75
8
4,256
31,524
304
1,296
10,400
183,760
48
16,560
1,760
64
504,240
240
1,575
8
Total ....................................
................................
..................................
................................
................................
4,350,287
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 4—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR BIOLOGICS 1
Number of recordkeepers
21 CFR Section
Annual frequency
per recordkeeping
Total annual
records
Hours per record
Total hours
312.52(a) ..................................
312.57(a) and (b) .....................
312.62(a) ..................................
312.62(b) ..................................
312.160(a)(3) ...........................
312.160(c) ................................
139
433
5,570
5,570
146
146
1.4
2.6
1
10
1.4
1.4
195
1,126
5,570
55,700
204
204
2
100
40
40
0.5
0.5
390
112,600
222,800
2,228,000
102
102
Total ..................................
................................
..................................
................................
..................................
2,563,994
1
There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: January 20, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
FOR FURTHER INFORMATION CONTACT:
Jonna Capezzuto, Office of Information
Management, Food and Drug
Administration, 1350 Piccard Dr., PI50–
400B, Rockville, MD 20850, 301–796–
3794, e-mail:
Jonnalynn.Capezzuto@fda.hhs.gov.
[FR Doc. 2011–1758 Filed 1–26–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–N–0084]
Agency Information Collection
Activities; Announcement of Office of
Management and Budget Approval;
Pretesting of Tobacco
Communications
AGENCY:
Food and Drug Administration,
HHS.
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ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a collection of information entitle
‘‘Pretesting of Tobacco
Communications’’ has been approved by
the Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995.
SUMMARY:
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17:51 Jan 26, 2011
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In the
Federal Register of August 6, 2010 (75
FR 47600), the Agency announced that
the proposed information collection had
been submitted to OMB for review and
clearance under 44 U.S.C. 3507. 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. OMB has now approved the
information collection and has assigned
OMB control number 0910–0674. The
approval expires on January 31, 2013. A
copy of the supporting statement for this
information collection is available on
the Internet at https://www.reginfo.gov/
public/do/PRAMain.
SUPPLEMENTARY INFORMATION:
Dated: January 21, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–1757 Filed 1–26–11; 8:45 am]
BILLING CODE 4160–01–P
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–N–0250]
Agency Information Collection
Activities; Announcement of Office of
Management and Budget Approval;
Premarket Approval of Medical
Devices
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a collection of information entitled
‘‘Premarket Approval of Medical
Devices’’ has been approved by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995.
FOR FURTHER INFORMATION CONTACT:
Daniel Gittleson, Office of Information
Management, Food and Drug
Administration, 1350 Piccard Dr., PI50–
400B, Rockville, MD 20850, 301–796–
5156, Daniel.Gittleson@FDA.HHS.GOV.
SUPPLEMENTARY INFORMATION: In the
Federal Register of September 24, 2010
SUMMARY:
E:\FR\FM\27JAN1.SGM
27JAN1
]]>Agencies
[Federal Register Volume 76, Number 18 (Thursday, January 27, 2011)]
[Notices]
[Pages 4914-4917]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-1758]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0042]
Agency Information Collection Activities: Proposed Collection;
Comment Request; Investigational New Drug Regulations
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the Agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on requirements under which the
clinical investigation of the safety and effectiveness of unapproved
new drugs and biological products can be conducted.
DATES: Submit either electronic or written comments on the collection
of information by March 28, 2011.
ADDRESSES: Submit electronic comments on the collection of information
to: https://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
P150-400B, Rockville, MD 20850. 301-796-3792.
Elizabeth.Berbakos@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
With respect to the following collection of information, FDA
invites 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, when
appropriate, and other forms of information technology.
Investigational New Drug (IND) Regulations--21 CFR Part 312 (OMB
Control Number 0910-0014)--Extension
FDA is requesting OMB approval for the reporting and recordkeeping
requirements contained in the FDA regulations ``Investigational New
Drug Application'' in part 312 (21 CFR part 312). Part 312 implements
provisions of section 505(i) of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 355(i)) (the FD&C Act) to issue regulations under which
the clinical investigation of the safety and effectiveness of
unapproved new drugs and biological products can be conducted.
FDA is charged with implementing statutory requirements that drug
products marketed in the United States be shown to be safe and
effective, properly manufactured, and properly labeled for their
intended uses. Section 505(a) of the act provides that a new drug may
not be introduced or delivered for introduction into interstate
commerce in the United States unless FDA has previously approved a new
drug application (NDA). FDA approves an NDA only if the sponsor of the
application first demonstrates that the drug is safe and effective for
the conditions prescribed, recommended, or suggested in the product's
labeling. Proof must consist, in part, of adequate and well-controlled
studies, including studies in humans, that are conducted by qualified
experts. The IND regulations establish reporting requirements that
include an initial application as well as amendments to that
application, reports on significant revisions of clinical investigation
plans, and information on a drug's safety or effectiveness. In
addition, the sponsor is required to give FDA an annual summary of the
previous year's clinical experience. Submissions are reviewed by
medical officers and other agency scientific reviewers assigned
responsibility for overseeing the specific study. The IND regulations
also contain recordkeeping requirements that pertain to the
responsibilities of sponsors and investigators. The detail and
complexity of these requirements are dictated by the scientific
procedures and human subject safeguards that must be followed in the
clinical tests of investigational new drugs.
The IND information collection requirements provide the means by
which FDA can do the following: (1) Monitor the safety of ongoing
clinical investigations; (2) determine whether the clinical testing of
a drug should be authorized; (3) ensure production of reliable data on
the metabolism and pharmacological action of the drug in humans; (4)
obtain timely information on adverse reactions to the drug; (5) obtain
information on side effects associated with increasing doses; (6)
obtain information on the drug's effectiveness; (7) ensure the design
of well-controlled, scientifically valid studies; (8) obtain other
information pertinent to determining whether clinical testing should be
continued and information related to the protection of human subjects.
Without the information provided by industry in response to the IND
regulations, FDA cannot authorize or monitor the clinical
investigations which must be conducted prior to authorizing the sale
and general use of new drugs. These reports enable FDA to monitor a
study's progress, to assure subject safety, to assure that a study will
be conducted ethically, and to increase the likelihood that the sponsor
will conduct studies that will be useful in determining whether the
[[Page 4915]]
drug should be marketed and available for use in medical practice.
There are two forms that are required under part 312:
Form FDA-1571--``Investigational New Drug Application''--A person
who intends to conduct a clinical investigation submits this form to
FDA. It includes the following information: (1) A cover sheet
containing background information on the sponsor and investigator, (2)
a table of contents, (3) an introductory statement and general
investigational plan, (4) an investigator's brochure describing the
drug substance, (5) a protocol for each planned study, (6) chemistry,
manufacturing, and control information for each investigation, (7)
pharmacology and toxicology information for each investigation, and (8)
previous human experience with the investigational drug.
Form FDA-1572--``Investigator Statement''--Before permitting an
investigator to begin participation in an investigation, the sponsor
must obtain and record this form. It includes background information on
the investigator and the investigation, and a general outline of the
planned investigation and the study protocol.
FDA is requesting OMB approval for the following reporting and
recordkeeping requirements in part 312:
Reporting Requirements
21 CFR 312.2(e)--Requests for FDA advice on the applicability of
part 312 to a planned clinical investigation.
21 CFR 312.8--Charging for investigational drugs under an IND.
21 CFR 312.10--Applications for waiver of requirements under part
312. As indicated in Sec. 312.10(a), estimates for this requirement
are included under Sec. Sec. 312.23 and 312.31. In addition,
separate requests under Sec. 312.10 are estimated in table 1 of
this document.
21 CFR 312.20(c)--Applications for investigations involving an
exception from informed consent under Sec. 50.24 (21 CFR 50.24).
Estimates for this requirement are included under Sec. 312.23.
21 CFR 312.23--INDs (content and format).
21 CFR 312.23(a)(1)--Cover sheet FDA-1571.
21 CFR 312.23(a)(2) --Table of Contents.
21 CFR 312.23(a)(3)--Investigational plan for each planned study.
21 CFR 312.23(a)(5)--Investigator's brochure.
21 CFR 312.23(a)(6)--Protocols--Phase 1, 2, and 3.
21 CFR 312.23(a)(7)--Chemistry, manufacturing, and control
information.
21 CFR 312.23(a)(7)(iv)(a),(b),(c)--A description of the drug
substance, a list of all components, and any placebo used.
21 CFR 312.23(a)(7)(iv)(d)--Labeling: Copies of labels and labeling
to be provided each investigator.
21 CFR 312.23(a)(7)(iv)(e)--Environmental impact analysis regarding
drug manufacturing and use.
21 CFR 312.23(a)(8)--Pharmacological and toxicology information.
21 CFR 312.23(a)(9)--Previous human experience with the
investigational drug.
21 CFR 312.23(a)(10)--Additional information.
21 CFR 312.23(a)(11)--Relevant information.
21 CFR 312.23(f)--Identification of exception from informed consent.
21 CFR 312.30--Protocol amendments.
21 CFR 312.30(a)--New protocol.
21 CFR 312.30(b)--Change in protocol.
21 CFR 312.30(c)--New investigator.
21 CFR 312.30(d)--Content and format.
21CFR 312.30(e)--Frequency.
21 CFR 312.31--Information amendments.
21CFR 312.31(b)--Content and format.
--Chemistry, toxicology, or technical information.
21 CFR 312.32--Safety reports.
21 CFR 312.32(c)(1)--Written reports to FDA and to investigators.
21 CFR 312.32(c)(2)--Telephone reports to FDA for fatal or life-
threatening experience.
21 CFR 312.32(c)(3)--Format or frequency.
21 CFR 312.32(d)--Follow up submissions.
21 CFR 312.33--Annual reports.
21 CFR 312.33(a)--Individual study information.
21 CFR 312.33(b)--Summary information.
21 CFR 312.33(b)(1)--Adverse experiences.
21 CFR 312.33(b)(2)--Safety report summary.
21 CFR 312.33(b)(3)--List of fatalities and causes of death.
21 CFR 312.33(b)(4)--List of discontinuing subjects.
21 CFR 312.33(b)(5)--Drug action.
21 CFR 312.33(b)(6)--Preclinical studies and findings.
21 CFR 312.33(b)(7)--Significant changes.
21 CFR 312.33(c)--Next year general investigational plan.
21 CFR 312.33(d)--Brochure revision.
21 CFR.312.33(e)--Phase I protocol modifications.
21 CFR.312.33(f)--Foreign marketing developments.
21 CFR 312.38(b) and (c)--Notification of withdrawal of an IND.
21 CFR 312.42(e)--Sponsor requests that a clinical hold be removed
and submits a complete response to the issues identified in the
clinical hold order.
21 CFR 312.44(c) and (d)--Opportunity for sponsor response to FDA
when IND is terminated.
21 CFR 312.45(a) and (b)--Sponsor request for, or response to,
inactive status determination of an IND.
21 CFR 312.47(b)--``End-of-Phase 2'' meetings and ``Pre-NDA''
meetings.
21 CFR 312.53(c)--Investigator information.
Investigator report (Form FDA-1572) and narrative; investigator's
background information; Phase 1 outline of planned investigation and
Phase 2 outline of study protocol.
21 CFR 312.54(a) and (b)--Sponsor submissions concerning
investigations involving an exception from informed consent under
Sec. 50.24.
21 CFR 312.55(b)--Sponsor reports to investigators on new
observations, especially adverse reactions and safe use. Only ``new
observations'' are estimated under this section; investigator
brochures are included under Sec. 312.23.
21 CFR 312.56(b),(c), and (d)--Sponsor monitoring of all clinical
investigations, investigators, and drug safety; notification to FDA.
21 CFR 312.58(a)--Sponsor's submission of records to FDA on request.
21 CFR 312.64--Investigator reports to the sponsor.
21 CFR 312.64(a)--Progress reports.
21 CFR 312.64(b)--Safety reports.
21 CFR 312.64(c)--Final reports.
21 CFR 312.66--Investigator reports to Institutional Review Board.
Estimates for this requirement are included under Sec. 312.53.
21 CFR 312.70(a)--Investigator disqualification; opportunity to
respond to FDA.
21 CFR 312.83--Sponsor submission of treatment protocol. Estimates
for this requirement are included under Sec. 312.320.
21 CFR 312.85--Sponsors conducting Phase 4 studies. Estimates for
this requirement are included under Sec. 312.23 in 0910-0014, and
Sec. Sec. 314.50, 314.70, and 314.81 in 0910-0001.
21 CFR 312.110(b)--Request to export an investigational drug.
21 CFR 312.120--Submissions related to foreign clinical studies not
conducted under an IND.
21 CFR 312.130(d)--Request for disclosable information for
investigations involving an exception from informed consent under
Sec. 50.24.
21 CFR 312.310(b); 312.305(b)--Submissions related to expanded
access and treatment of an individual patient.
21 CFR 312.310(d)--Submissions related to emergency use of an
investigational new drug.
21 CFR 312.315(c); 312.305(b)--Submissions related to expanded
access and treatment of an intermediate size patient population.
21 CFR 312.320--Submissions related to treatment IND or treatment
protocol.
Recordkeeping Requirements
21 CFR 312.52(a)--Transfer of obligations to a contract research
organization.
21 CFR 312.57--Sponsor recordkeeping.
21 CFR 312.59--Sponsor recordkeeping of disposition of unused supply
of drugs. Estimates for this requirement are included under Sec.
312.57.
21 CFR 312.62(a)--Investigator recordkeeping of disposition of
drugs.
21 CFR 312.62(b)--Investigator recordkeeping of case histories of
individuals.
21 CFR 312.120(d)--Recordkeeping requirements for submissions
related to foreign clinical studies not conducted under an IND.
Estimates for this requirement are included under Sec. 312.57.
21 CFR 312.160(a)(3)--Records maintenance: shipment of drugs for
investigational use in laboratory research animals or in vitro
tests.
21 CFR 312.160(c)--Shipper records of alternative disposition of
unused drugs.
[[Page 4916]]
In the tables in this document, the estimates for ``No. of
Respondents,'' ``Annual Frequency per Response,'' and ``Total Annual
Responses'' were obtained from the Center for Drug Evaluation and
Research (CDER) and the Center for Biologics Evaluation and Research
(CBER) reports and data management systems for submissions received in
2007 and from other sources familiar with the number of submissions
received under part 312. The estimates for ``Hours per Response'' were
made by CDER and CBER individuals familiar with the burden associated
with these reports and from estimates received from the pharmaceutical
industry.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden for Human Drugs \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annual frequency Total annual
21 CFR section No. of respondents per response responses Hours per response Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
312.2(e)........................................... 455 1.03 469 24 11,256
312.8.............................................. 30 1.13 34 48 1,632
312.10............................................. 4 1 4 10 40
312.23(a) through (f).............................. 2,496 1.26 3,145 1,600 5,032,000
312.30(a) through (e).............................. 2,030 8.91 18,087 284 5,136,708
312.31 (b)......................................... 153 2.97 454 100 45,400
312.32(c) and (d).................................. 985 23.06 22,714 32 726,848
312.33(a) through (f).............................. 2,564 2.34 6,000 360 2,160,000
312.38(b) and (c).................................. 654 1.34 876 28 24,528
312.42(e).......................................... 149 1.10 164 284 46,576
312.44(c) and (d).................................. 44 1 44 16 704
312.45(a) and (b).................................. 254 1.43 363 12 4,356
312.47(b).......................................... 281 1.8 506 160 80,960
312.53(c).......................................... 21,194 1 21,194 80 1,695,520
312.54(a) and (b).................................. 0 0 0 48 0
312.55(b).......................................... 985 2,306 2,271,410 48 109,027,680
312.56(b), (c), and (d)............................ 18 1 18 80 1,440
312.58(a).......................................... 91 4.10 373 8 2,984
312.64............................................. 31,791 1 31,791 24 762,984
312.70(a).......................................... 4 1 4 40 160
312.110(b)......................................... 23 18.26 420 75 31,500
312.120............................................ 115 5 575 32 18,400
312.130(d)......................................... 3 1 3 8 24
312.310(b) and 312.305(b).......................... 988 1 988 8 7,904
312.310(d)......................................... 525 1.23 646 16 10,336
312.315(c) and 312.305(b).......................... 68 1 68 120 8,160
312.320............................................ 9 1.11 10 300 3,000
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Total.......................................... .................. ................... .................. .................. 124,841,100
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 2--Estimated Annual Recordkeeping Burden for Human Drugs \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Annual frequency Total annual
21 CFR Section recordkeepers per recordkeeping records Hours per record Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
312.52(a)......................................... 335 1.5 503 2 1,006
312.57............................................ 75 485.28 36,396 100 3,639,600
312.62(a)......................................... 14,732 1 14,732 40 589,280
312.62(b)......................................... 147,320 1 147,320 40 5,892,800
312.160(a)(3)..................................... 547 1.4 766 .5 383
312.160(c)........................................ 547 1.4 766 .5 383
-----------------------------------------------------------------------------------------------------
Total......................................... .................. ................... .................. ................... 10,123,452
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 3--Estimated Annual Reporting Burden for Biologics \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annual frequency Total annual
21 CFR Section No. of respondents per response responses Hours per response Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
312.7(d)........................................... 41 1.4 57 24 1,368
312.23(a) through (f) and 312.120(b), (c)(2), and 433 1.3 563 1,808 1,017,904
(c)(3)............................................
312.30(a) through (e).............................. 590 6.8 4,012 284 1,139,408
312.31(b).......................................... 263 29.3 7,706 100 770,600
312.32(c) and (d) and 312.56(c).................... 294 13.7 4,028 32 128,896
312.33(a) through (f) and 312.56(c)................ 647 2.3 1,488 360 535,680
312.35(a) and (b).................................. 1 1 1 300 300
312.36............................................. 6 1 6 16 96
[[Page 4917]]
312.38(b) and (c).................................. 117 1.3 152 28 4,256
312.42(e).......................................... 74 1.5 111 284 31,524
312.44(c) and (d).................................. 17 1.1 19 16 304
312.45(a) and (b).................................. 60 1.8 108 12 1,296
312.47(b).......................................... 43 1.5 65 160 10,400
312.53(c).......................................... 348 6.6 2,297 80 183,760
312.54(a) and (b).................................. 1 1 1 48 48
312.55(b).......................................... 138 2.5 345 48 16,560
312.56(b) and (d).................................. 14 1.6 22 80 1,760
312.58(a).......................................... 8 1 8 8 64
312.64(a) through (d).............................. 6,003 3.5 21,010 24 504,240
312.70(a).......................................... 6 1 6 40 240
312.110(b)......................................... 21 1 21 75 1,575
312.130(d)......................................... 1 1 1 8 8
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Total.......................................... .................. ................... .................. .................. 4,350,287
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 4--Estimated Annual Recordkeeping Burden for Biologics \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Annual frequency Total annual
21 CFR Section recordkeepers per recordkeeping records Hours per record Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
312.52(a)......................................... 139 1.4 195 2 390
312.57(a) and (b)................................. 433 2.6 1,126 100 112,600
312.62(a)......................................... 5,570 1 5,570 40 222,800
312.62(b)......................................... 5,570 10 55,700 40 2,228,000
312.160(a)(3)..................................... 146 1.4 204 0.5 102
312.160(c)........................................ 146 1.4 204 0.5 102
-----------------------------------------------------------------------------------------------------
Total......................................... .................. ................... .................. ................... 2,563,994
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: January 20, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-1758 Filed 1-26-11; 8:45 am]
BILLING CODE 4160-01-P
