[Federal Register: February 17, 2006 (Volume 71, Number 33)]
[Notices]
[Page 8590-8595]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17fe06-73]
[[Page 8590]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005N-0393]
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.
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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 March
20, 2006.
ADDRESSES: OMB is still experiencing significant delays in the regular
mail, including first class and express mail, and messenger deliveries
are not being accepted. 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: Fumie
Yokota, Desk Officer for FDA, FAX: 202-395-6974.
FOR FURTHER INFORMATION CONTACT: Karen Nelson, Office of Management
Programs (HFA-250), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-1482.
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 Regulations--(OMB Control Number 0910-0014)--
Extension
FDA is requesting OMB approval for the reporting and recordkeeping
requirements contained in the FDA regulation ``Investigational New Drug
Application'' in part 312 (21 CFR part 312). This regulation implements
provisions of section 505(i) of the Federal Food, Drug, and Cosmetic
Act (the 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 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
drug should be marketed and available for use in medical practice.
There are two forms that are required under part 312. The first is
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.
The second form required under part 312 is 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.
In the Federal Register of October 12, 2005 (70 FR 59350), FDA
published a 60-day notice requesting public comments on the information
collection provisions. No comments were received that pertained to the
information collection burden estimates.
FDA is requesting OMB approval for the following reporting and
recordkeeping requirements in part 312:
Table 1.
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REPORTING REQUIREMENTS
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21 CFR Section Requirements
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312.7(d).......................... Applications for permission to sell
an investigational new drug.
[[Page 8591]]
312.10(a)......................... Applications for waiver of
requirements under part 312.
Estimates for this requirement are
included under Sec. Sec. 312.23
and 312.31.
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.
312.23............................ INDs (content and format).
(a)(1).......................... Cover sheet FDA-1571.
(a)(2).......................... Table of contents.
(a)(3).......................... Investigational plan for each
planned study.
(a)(5).......................... Investigator's brochure.
(a)(6).......................... Protocols--phases 1, 2, and 3.
(a)(7).......................... Chemistry, manufacturing, and
control information.
(a)(7)(iv)(a), (a)(7)(iv)(b), A description of the drug
and (a)(7)(iv)(c) substance, a list of all components,
and any placebo used.
(a)(7)(iv)(d)................... Labeling: Copies of labels and
labeling to be provided each
investigator.
(a)(7)(iv)(e)................... Environmental impact analysis
regarding drug manufacturing and
use.
(a)(8).......................... Pharmacological and toxicology
information.
(a)(9).......................... Previous human experience with the
investigational drug.
(a)(10)......................... Additional information.
(a)(11)......................... Relevant information.
(f)............................. Identification of exception from
informed consent.
312.30............................ Protocol amendments.
(a)............................. New protocol.
(b)............................. Change in protocol.
(c)............................. New investigator.
(d)............................. Content and format.
(e)............................. Frequency.
312.31............................ Information amendments.
(b)............................. Content and format.
Chemistry, toxicology, or technical
information.
312.32............................ Safety reports.
(c)(1).......................... Written reports to FDA and to
investigators.
(c)(2).......................... Telephone reports to FDA for fatal
or life-threatening experience.
(c)(3).......................... Format or frequency.
(d)............................. Followup submissions.
312.33............................ Annual reports.
(a)............................. Individual study information.
(b)............................. Summary information.
(b)(1).......................... Adverse experiences.
(b)(2).......................... Safety report summary.
(b)(3).......................... List of fatalities and causes of
death.
(b)(4).......................... List of discontinuing subjects.
(b)(5).......................... Drug action.
(b)(6).......................... Preclinical studies and findings.
(b)(7).......................... Significant changes.
(c)............................. Next year general investigational
plan.
(d)............................. Brochure revision.
(e)............................. Phase I protocol modifications.
(f)............................. Foreign marketing developments.
312.35............................ Treatment use of investigational new
drugs.
(a)............................. Treatment protocol submitted by an
investigational new drug sponsor.
(b)............................. Treatment investigational new drug
application (IND) submitted by
licensed practitioner.
312.36............................ Requests for emergency use of an
investigational new drug.
312.38(b) and (c)................. Notification of withdrawal of an
investigational new drug.
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.
312.44(c) and (d)................. Opportunity for sponsor response to
FDA when an investigational new
drug is terminated.
312.45(a) and (b)................. Sponsor request for, or response to,
inactive status determination of an
investigational new drug.
312.47(b)......................... ``End-of-Phase 2'' meetings and
``Pre-NDA'' meetings.
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; financial disclosure
information.
312.54(a) and (b)................. Sponsor submissions concerning
investigations involving an
exception from informed consent
under Sec. 50.24.
[[Page 8592]]
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.
312.56(b), (c), and (d)........... Sponsor monitoring of all clinical
investigations, investigators, and
drug safety; notification to FDA.
312.58(a)......................... Sponsor's submission of records to
FDA on request.
312.64............................ Investigator reports to the sponsor.
(a)............................. Progress reports.
(b)............................. Safety reports
(c)............................. Final reports.
(d)............................. Financial disclosure reports.
312.66............................ Investigator reports to
Institutional Review Board.
Estimates for this requirement are
included under Sec. 312.53.
312.70(a)......................... Investigator disqualification;
opportunity to respond to FDA.
312.83............................ Sponsor submission of treatment
protocol. Estimates for this
requirement are included under Sec.
Sec. 312.34 and 312.35.
312.85............................ Sponsors conducting phase 4 studies.
Estimates for this requirement are
included under Sec. 312.23 in OMB
control number 0910-0014, and Sec.
Sec. 314.50, 314.70, and 314.81
(21 CFR 314.50, 314.70, and 314.81)
in OMB control number 0910-0001.
312.110(b)........................ Request to export an investigational
drug.
312.120(b) and (c)(2)............. Sponsor's submission to FDA for use
of foreign clinical study to
support an IND. Estimates for this
requirement are included under Sec.
Sec. 312.23 and 312.30 in OMB
control number 0910-0014, and Sec.
Sec. 314.50, 314.60, and 314.70
(21 CFR 314.60) in OMB control
number 0910-0001.
312.120(c)(3)..................... Sponsor's report to FDA on findings
of independent review committee on
foreign clinical study. Estimates
for this requirement are included
under Sec. Sec. 312.23 and
312.30 in OMB control number 0910-
0014, and Sec. Sec. 314.50,
314.60, and 314.70 in OMB control
number 0910-0001.
312.130(d)........................ Request for disclosable information
for investigations involving an
exception from informed consent
under Sec. 50.24.
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312.52(a)......................... Transfer of obligations to a
contract research organization.
312.57(a) and (b)................. Sponsor recordkeeping.
312.59............................ Sponsor recordkeeping of disposition
of unused supply of drugs.
Estimates for this requirement are
included under Sec. 312.57.
312.62(a)......................... Investigator recordkeeping of
disposition of drugs.
312.62(b)......................... Investigator recordkeeping of case
histories of individuals.
312.160(a)(3)..................... Records maintenance: shipment of
drugs for investigational use in
laboratory research animals or in
vitro tests.
312.160(c)........................ Shipper records of alternative
disposition of unused drugs.
In tables 2 and 3 of this document, the estimates for ``No. of
Respondents,'' ``No. of Responses per Respondent,'' 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
2004 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 2.--Estimated Annual Reporting and Recordkeeping Burden for Human Drugs\1\
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REPORTING BURDEN
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No. of No. of Responses Total Annual Hours per
21 CFR Section Respondents per Respondent Responses Response Total Hours
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312.7(d) 9 1.4 13 24 7,488
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312.23(a) through (f) 1,245 1.3 1,597 1,600 2,555,200
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[[Page 8593]]
312.30(a) through (e) 1,257 13.3 16,687 284 4,739,108
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312.31(b) 1,116 7.4 8,298 100 829,800
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312.32(c) and (d) 649 24.7 16,052 32 513,664
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312.33(a) through (f) 1,821 2.5 4,516 360 1,625,760
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312.35(a) and (b) 5 1.2 6 300 1,800
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312.36 109 1.1 121 16 1,936
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312.38(b) and (c) 536 1.3 677 28 18,965
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312.42(e) 97 1.2 118 284 33,512
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312.44(c) and (d) 44 1 45 16 720
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312.45(a) and (b) 185 1.5 271 12 3,252
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312.47(b) 215 1.7 355 160 56,800
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312.53(c) 21,194 1 21,194 80 1,695,520
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312.54(a) and (b) 0 0 0 48 0
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312.55(b) 807,400 1 807,400 48 38,755,200
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312.56(b), (c), and (d) 13 1 13 80 1,040
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312.58(a) 88 3.8 340 8 2,720
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312.64(a) through (d) 31,791 1 31,791 24 762,984
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312.70(a) 4 1 4 40 160
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312.110(b) 33 8.3 276 75 20,700
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312.130(d) 5 1 5 8 40
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Total reporting burden 51,626,369
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RECORDKEEPING BURDEN
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No. of No. of Records Total Annual Hours per
21 CFR Section Recordkeepers per Recordkeeper Records Record Total Hours
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312.52(a) 335 1.5 488 2 976
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312.57(a) and (b) 335 119.8 40,148 100 4,014,800
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312.62(a) 20,074 1 20,074 40 802,960
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312.62(b) 200,740 1 200,740 40 8,029,600
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312.160(a)(3) 372 1.5 542 .5 271
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312.160(c) 372 1.5 542 .5 271
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Total recordkeeping burden 12,848,878
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Human drugs total burden hours 64,475,247
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 8594]]
Table 3.--Estimated Annual Reporting and Recordkeeping Burden for Biologics\1\
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REPORTING BURDEN
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No. of No. of Responses Total Annual Hours per
21 CFR Section Respondents per Respondent Responses Response Total Hours
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312.7(d) 41 1.4 58 24 1,392
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312.23(a) through (f) and 433 1.3 557 1,808 1,007,056
312.120(b), (c)(2), and (c)(3)
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312.30(a) through (e) 590 6.8 4,014 284 1,139,976
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312.31(b) 263 29.3 7,700 100 770,000
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312.32(c) and (d) and 312.56(c) 294 13.7 4,042 32 129,344
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312.33(a) through (f) and 647 2.3 1,473 360 530,280
312.56(c)
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312.35(a) and (b) 1 1 1 300 300
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312.36 6 1 6 16 96
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312.38(b) and (c) 117 1.3 153 28 4,284
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312.42(e) 74 1.5 108 284 30,672
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312.44(c) and (d) 17 1.1 18 16 288
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312.45(a) and (b) 60 1.8 107 12 1,284
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312.47(b) 43 1.5 66 160 10,560
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312.53(c) 348 6.6 2,303 80 184,240
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312.54(a) and (b) 1 1 1 48 48
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312.55(b) 138 2.5 347 48 16,656
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312.56(b) and (d) 14 1.6 23 80 1,840
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312.58(a) 8 1 8 8 64
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312.64(a) through (d) 6,003 3.5 21,185 24 508,440
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312.70(a) 6 1 6 40 240
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312.110(b) 21 1 21 75 1,575
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312.130(d) 1 1 1 8 8
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Total reporting burden 4,338,643
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RECORDKEEPING BURDEN
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No. of Annual Frequency Total Annual Hours per
21 CFR Section Recordkeepers per Recordkeeping Records Record Total Hours
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312.52(a) 139 1.4 200 2 400
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312.57(a) and (b) 433 2.6 1,114 100 111,400
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312.62(a) 5,570 1 5,570 40 222,800
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312.62(b) 5,570 10 55,700 40 2,228,000
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312.160(a)(3) 146 1.4 211 0.5 105.5
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312.160(c) 146 1.4 211 0.5 105.5
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Total recordkeeping burden 2,562,811
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Total biologics burden hours 6,901,454
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 8595]]
Table 4.--Estimated Annual Reporting and Recordkeeping Burden for Human
Drugs and Biologics\1\
Total human drugs burden hours.......................... 64,475,247
Total biologics burden hours............................ 6,901,454
Total burden hours...................................... 71,376,701
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\1\ There are no capital costs or operating and maintenance costs
associated with this collection of information.
Dated: February 9, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-2289 Filed 2-16-06; 8:45 am]
BILLING CODE 4160-01-S