[Federal Register Volume 76, Number 18 (Thursday, January 27, 2011)]
[Notices]
[Pages 4914-4917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-1758]
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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.
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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: http://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.
[email protected].
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\
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Annual frequency Total annual
21 CFR section No. of respondents per response responses Hours per response Total hours
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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
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\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\
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Number of Annual frequency Total annual
21 CFR Section recordkeepers per recordkeeping records Hours per record Total hours
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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
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Total......................................... .................. ................... .................. ................... 10,123,452
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\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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Annual frequency Total annual
21 CFR Section No. of respondents per response responses Hours per response Total hours
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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
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\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\
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Number of Annual frequency Total annual
21 CFR Section recordkeepers per recordkeeping records Hours per record Total hours
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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
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Total......................................... .................. ................... .................. ................... 2,563,994
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\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