Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Investigational New Drug Regulations, 27328-27331 [2011-11540]
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27328
Federal Register / Vol. 76, No. 91 / Wednesday, May 11, 2011 / Notices
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Dated: May 5, 2011.
Elaine L. Baker,
Director, Management Analysis and Services
Office, Centers for Disease Control and
Prevention.
[FR Doc. 2011–11526 Filed 5–10–11; 8:45 am]
BILLING CODE 4163–18–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–N–0042]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Investigational
New Drug Regulations
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by June 10,
2011.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, FAX:
202–395–7285, or e-mailed to
oira_submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0014. Also
include the FDA docket number found
in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT:
Elizabeth Berbakos, Office of
Information Management, Food and
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SUMMARY:
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Drug Administration, 1350 Piccard Dr.,
PI50–400B, Rockville, MD 20850, 301–
796–3792,
Elizabeth.Berbakos@fda.hhs.gov.
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
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 (the FD&C Act) (21
U.S.C. 355(i)) 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 FD&C 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 INDs.
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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; and (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
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:
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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.
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—Phases
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.
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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. Only ‘‘new observations’’
are estimated under this section;
investigator brochures are included
under § 312.23.
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27329
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.
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Federal Register / Vol. 76, No. 91 / Wednesday, May 11, 2011 / Notices
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.
In the tables below, 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.
In the Federal Register of January 27,
2011 (76 FR 4914), FDA published a 60day notice requesting public comment
on the proposed collection of
information. No comments were
received.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN FOR HUMAN DRUGS 1
Number of
responses per
respondent
Number of
respondents
21 CFR Section
Average
burden per
response
(in hours) 2
Total annual
responses
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
45
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.
estimates of less than 1 hour are expressed as a fraction of an hour in the format ‘‘[number of minutes per response]/60’’.
2 Burden
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR HUMAN DRUGS 1
Number of
recordkeepers
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21 CFR Section
Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
(in hours) 2
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
30/60
30/60
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.
estimates of less than 1 hour are expressed as a fraction of an hour in the format ‘‘[number of minutes per response]/60’’.
2 Burden
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Federal Register / Vol. 76, No. 91 / Wednesday, May 11, 2011 / Notices
TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN FOR BIOLOGICS 1
Number of
responses per
respondent
Number of
respondents
21 CFR Section
Average
burden per
response
(in hours) 2
Total annual
responses
Total hours
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 ................................................................................
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) ..........................................................................
41
433
590
263
294
647
1
6
117
74
17
60
43
348
1
138
14
8
6,003
6
21
1
1.4
1.3
6.8
29.3
13.7
2.3
1
1
1.3
1.5
1.1
1.8
1.5
6.6
1
2.5
1.6
1
3.5
1
1
1
57
563
4,012
7,706
4,028
1,488
1
6
152
111
18
108
65
2,297
1
345
22
8
21,010
6
21
1
24
1,808
284
100
32
360
300
16
28
284
16
12
160
80
48
48
80
8
24
40
75
8
1,368
1,017,904
1,139,408
770,600
128,896
535,680
300
96
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.
estimates of less than 1 hour are expressed as a fraction of an hour in the format ‘‘[number of minutes per response]/60’’.
2 Burden
TABLE 4—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR BIOLOGICS 1
Number of
recordkeepers
Number of
records per
recordkeeper
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
Total ............................................................................
........................
21 CFR Section
1 There
..........................
Total annual
records
Average
burden per
recordkeeping
(in hours) 2
Total hours
195
1,126
5,570
55,700
204
204
2
100
40
40
30/60
30/60
390
112,600
222,800
2,228,000
102
102
........................
........................
2,563,994
are no capital costs or operating and maintenance costs associated with this collection of information.
estimates of less than 1 hour are expressed as a fraction of an hour in the format ‘‘[number of minutes per response]/60’’.
2 Burden
Dated: May 6, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–11540 Filed 5–10–11; 8:45 am]
mstockstill on DSKH9S0YB1PROD with NOTICES
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–D–0272]
Draft Guidance for Industry and Food
and Drug Administration Staff;
Establishing the Performance
Characteristics of In Vitro Diagnostic
Devices for Chlamydia Trachomatis
and/or Neisseria Gonorrhoeae:
Screening and Diagnostic Testing;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
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Notice.
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The Food and Drug
Administration (FDA) is announcing the
availability of the draft guidance
entitled ‘‘Establishing the Performance
Characteristics of In Vitro Diagnostic
Devices for Chlamydia Trachomatis
and/or Neisseria Gonorrhoeae:
Screening and Diagnostic Testing.’’ This
draft guidance document provides
industry and Agency staff with
recommendations for studies to
establish the analytical and clinical
performance of in vitro diagnostic
devices (IVDs) intended for C.
trachomatis and/or N. gonorrhoeae
screening and diagnostic testing using
nucleic acid based assays. This draft
guidance is not final nor is it in effect
at this time.
SUMMARY:
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]]>Agencies
[Federal Register Volume 76, Number 91 (Wednesday, May 11, 2011)]
[Notices]
[Pages 27328-27331]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-11540]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0042]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Investigational New
Drug Regulations
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by June
10, 2011.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
FAX: 202-395-7285, or e-mailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-0014.
Also include the FDA 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.,
PI50-400B, Rockville, MD 20850, 301-796-3792,
Elizabeth.Berbakos@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
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 (the FD&C Act) (21 U.S.C. 355(i)) 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 FD&C 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 INDs.
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; and (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
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:
[[Page 27329]]
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.
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--Phases 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.
[[Page 27330]]
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.
In the tables below, 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.
In the Federal Register of January 27, 2011 (76 FR 4914), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden for Human Drugs \1\
----------------------------------------------------------------------------------------------------------------
Average
Number of Number of Total annual burden per
21 CFR Section respondents responses per responses response (in Total hours
respondent hours) \2\
----------------------------------------------------------------------------------------------------------------
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 45 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
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 124,841,100
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
minutes per response]/60''.
Table 2--Estimated Annual Recordkeeping Burden for Human Drugs \1\
----------------------------------------------------------------------------------------------------------------
Average
Number of Number of Total annual burden per
21 CFR Section recordkeepers records per records recordkeeping Total hours
recordkeeper (in hours) \2\
----------------------------------------------------------------------------------------------------------------
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 30/60 383
312.160(c)...................... 547 1.4 766 30/60 383
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 10,123,452
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
minutes per response]/60''.
[[Page 27331]]
Table 3--Estimated Annual Reporting Burden for Biologics \1\
----------------------------------------------------------------------------------------------------------------
Average
Number of Number of Total annual burden per
21 CFR Section respondents responses per responses response (in Total hours
respondent hours) \2\
----------------------------------------------------------------------------------------------------------------
312.7(d)....................... 41 1.4 57 24 1,368
312.23(a) through (f) and 433 1.3 563 1,808 1,017,904
312.120(b), (c)(2), and (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 647 2.3 1,488 360 535,680
312.56(c).....................
312.35(a) and (b).............. 1 1 1 300 300
312.36......................... 6 1 6 16 96
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 18 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
--------------------------------------------------------------------------------
Total...................... .............. ............... .............. .............. 4,350,287
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
minutes per response]/60''.
Table 4--Estimated Annual Recordkeeping Burden for Biologics \1\
----------------------------------------------------------------------------------------------------------------
Average
Number of Number of Total annual burden per
21 CFR Section recordkeepers records per records recordkeeping Total hours
recordkeeper (in hours) \2\
----------------------------------------------------------------------------------------------------------------
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 30/60 102
312.160(c)...................... 146 1.4 204 30/60 102
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 2,563,994
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
minutes per response]/60''.
Dated: May 6, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-11540 Filed 5-10-11; 8:45 am]
BILLING CODE 4160-01-P
