[Federal Register Volume 64, Number 155 (Thursday, August 12, 1999)]
[Notices]
[Pages 44019-44023]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-20846]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 99N-1010]
Agency Information Collection Activities; Submission for OMB
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 the
proposed collection of information listed below has been submitted to
the Office of Management and Budget (OMB) for review and clearance
under the Paperwork Reduction Act of 1995 (the PRA).
DATES: Submit written comments on the collection of information by
September 13, 1999.
ADDRESSES: Submit written comments on the collection of information to
the Office of Information and Regulatory Affairs, OMB, New Executive
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn:
Wendy Taylor, Desk Officer for FDA.
FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information
Resources Management (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-1482.
SUPPLEMENTARY INFORMATION: In compliance with section 3507 of the PRA
(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)-- Renewal
FDA is requesting OMB approval for the reporting and recordkeeping
requirements contained in FDA's regulation ``Investigational New Drug
Application'' 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
[[Page 44020]]
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: (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: Form FDA-
1571-- ``Investigational New Drug Application.''A person who intends to
conduct a clinical investigation submits this form to FDA. It includes:
(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:
Table 1.--Reporting Requirements
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21 CFR Section Explanations
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312.7(d)............................ Applications for permission to
sell an investigational new
drugs.
312.10(a)........................... Applications for waiver of
requirements under part 312.
Only emergency requests are
estimated under this section;
other requests are included
under Secs. 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.............................. IND's (content and format).
312.23(a)(1)........................ Cover sheet FDA-1571.
312.23(a)(2)........................ Table of contents.
312.23(a)(3)........................ Investigational plan for each
planned study.
312.23(a)(5)........................ Investigator's brochure.
312.23(a)(6)........................ Protocols--Phase 1, 2, and 3.
312.23(a)(7)........................ Chemistry, manufacturing, and
control information.
312.23(a)(7)(iv)(a), (b), and (c)... A description of the drug
substance, a list of all
components, and any placebo
used.
312.23(a)(7)(iv)(d)................. Labeling--copies of labels and
labeling to be provided each
investigator.
312.23(a)(7)(iv)(e)................. Environmental impact analysis
regarding drug manufacturing and
use.
312.23(a)(8)........................ Pharmacological and toxicology
information.
312.23(a)(9)........................ Previous human experience with
the investigational drug.
312.23(a)(10)....................... Additional information.
312.23(a)(11)....................... Relevant information.
312.23(f)........................... Identification of exception from
informed consent.
312.30.............................. Protocol amendments.
312.30(a)........................... New protocol.
312.30(b)........................... Change in protocol.
312.30(c)........................... New investigator.
312.30(d)........................... Content and format.
312.30(e)........................... Frequency.
312.31.............................. Information amendments.
312.31(b)........................... Content and format.
.................................. Chemistry, toxicology, or
technical information.
312.32.............................. Safety reports.
312.32(c)(1)........................ Written reports to FDA and to
investigators.
312.32(c)(2)........................ Telephone reports to FDA for
fatal or life-threatening
experience.
312.32(c)(3)........................ Format or frequency.
312.32(d)........................... Followup submissions.
312.33.............................. Annual reports.
312.33(a)........................... Individual study information.
312.33(b)........................... Summary information.
312.33(b)(1)........................ Adverse experiences.
312.33(b)(2)......................... Safety report summary.
312.33(b)(3)......................... List of fatalities and causes of
death.
312.33(b)(4)......................... List of discontinuing subjects.
[[Page 44021]]
312.33(b)(5)......................... Drug action.
312.33(b)(6)......................... Preclinical studies and findings.
312.33(b)(7)......................... Significant changes.
312.33(c)........................... Next year general investigational
plan.
312.33(d)........................... Brochure revision.
312.33(e)........................... Phase I protocol modifications.
312.33(f)........................... Foreign marketing developments.
312.35.............................. Treatment use of investigational
new drugs.
312.35(a)........................... Treatment protocol submitted by
IND sponsor.
312.35(b)........................... Treatment IND submitted by
licensed practitioner.
312.36.............................. Requests for emergency use of an
investigational new drugs.
312.38(b) and (c)................... Notification of withdrawal of an
IND.
312.44(c) and (d)................... Opportunity for sponsor response
to FDA when IND is terminated.
312.45(a) and (b)................... Sponsor request for or response
to inactive status determination
of an IND.
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.
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.
312.64(a)........................... Progress reports.
312.64(b)........................... Safety reports.
312.64(c)........................... Final reports.
312.64(d)........................... Financial disclosure reports.
312.66.............................. Investigator reports to
Institutional Review Board.
Estimates for this requirement
are included under Sec. 312.53.
312.70.............................. Investigator disqualification;
opportunity to respond to FDA.
Estimates for this requirement
are not included in the
estimates for part 312.
312.83.............................. Sponsor submission of treatment
protocol. Estimates for this
requirement are included under
Secs. 312.34 and 312.35.
312.85.............................. Sponsors conducting phase 4
studies. Estimates for these
postmarketing studies are not
included in the estimates for
part 312.
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.
312.120(c)(3)....................... Sponsor's report to FDA on
findings of independent review
committee on foreign clinical
study.
312.130(d).......................... Request for disclosable
information for investigations
involving an exception from
informed consent under Sec.
50.24.
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Table 2.--Recordkeeping Requirements
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21 CFR Section Explanations
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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).......................... 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.
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In the Federal Register of May 6, 1999 (64 FR 24402), the agency
requested comments on the proposed collections of information. No
comments were received.
[[Page 44022]]
Table 3.--Estimated Annual Reporting Burden for Human Drugs\1\
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No. of
No. of Responses Total Annual Hours per
21 CFR Section Respondents Per Responses Response Total Hours
Respondent
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312.7(d) 7 1 7 24 168
312.10(a) 0 0 0 0 0
312.23(a) and (f) 1,601 1.25 1,996 1,600 3,193,600
312.30(a) through (e) 918 14.85 13,629 284 3,870,636
312.31(b) 760 8.87 6,738 100 673,800
312.32(c) and (d) 459 14.33 6,576 32 210,432
312.33(a) through (f) 1,841 2.35 4,318 350 1,511,300
312.35(a) and (b) 1 1 1 300 300
312.36 643 1.2 720 16 11,520
312.38(b) 621 1.24 773 28 21,644
312.38(c) 621 1.24 773 160 123,680
312.44(c) and (d) 710 1.10 780 16 12,480
312.45(a) and (b) 294 1.32 389 12 4,668
312.47(b) 252 1 252 160 40,320
312.53(c) 4,500 1 4,500 80 360,000
312.54(a) and (b) 4 1 4 48 192
312.55(b) 4,500 1 4,500 48 216,000
312.56(b), (c), and (d) 5 1 5 80 400
312.58(a) 337 1 337 8 2,696
312.64(a) through (d) 8,200 1 8,200 24 196,800
312.110(b) 150 2 303 75 22,725
312.120(b) and (c)(2) 100 2 200 168 33,600
312(c)(3) 100 2 200 40 8,000
312.130(d) 4 1 4 8 32
Total Reporting Burden 10,514,993
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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 Human Drugs\1\
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Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
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312.52(a) 360 1 360 2 720
312.57(a) and (b) 4,000 2.05 8,200 100 400,000
312.62(a) 8,200 1 8,200 40 328,000
312.62(b) 8,200 12.2 100,000 40 328,000
312.160(a) 3,400 7.35 25,000 30 min 1,700
312.160(c) 3,400 2.35 8,000 30 min 1,700
Total Recordkeeping 1,060,120
Burden
Human Drugs Total Burden 11,575,113
Hours
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 5.--Estimated Annual Reporting Burden for Biologics\1\
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No. of
21 CFR Section No. of Responses Total Annual Hours per Total Hours
Respondents Per Response Responses Response
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312.7(d) 9 1.3 12 24 288
312.10(a) 1 1 1 40 40
312.23(a) and (f) and 312.120(b), 278 1.8 492 1,600 787,200
(c)(2), and (c)(3)
312.30(a) and (e) 975 6.5 6,411 284 1,820,724
312.31(b) 975 9.2 9,005 100 900,500
312.32(c) and (d) and 312.56(c) 602 6.7 4,034 32 129,088
312.33(a) and (f) and 312.56(c) 1,253 1.6 1,989 350 696,150
312.35(a) and (b) 1 1 1 300 300
312.36 22 5.5 122 16 1,952
312.38(b) 128 1.7 212 28 5,936
312.38(c) 128 1.7 212 160 33,920
312.44(c) and (d) 55 1.9 107 16 1,712
312.45(a) and (b) 74 1.4 105 12 1,260
312.47(b) 150 1.8 274 160 43,840
312.53(c) 672 6.6 4,421 80 353,680
312.54(a) and (b) 4 1 4 48 192
312.55(b) 374 6.1 2,288 48 109,824
312.56(b) and (d) 12 1.6 20 80 1,600
312.58(a) 10 1 10 8 80
312.64(a) and (d) 5,014 1 5,014 24 120,336
[[Page 44023]]
312.110(b) 10 1.3 13 75 975
312.130(d) 1 1 1 0.5 0.5
Total Reporting Burden 5,009,597.5
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 6.--Estimated Annual Recordkeeping Burden for Biologics\1\
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Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
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312.52(a) 27 2.5 67 5 135
312.57(a) and (b) 1,253 2 2,506 100 125,300
312.62(a) 5,014 1 5,014 40 200,560
312.62(b) 8,200 12.2 100,000 40 328,000
312.160(a) 3,400 7.35 25,000 30 min 1,700
312.160(c) 320 1 320 0.5 160
Total Biologics 655,855
Recordkeeping Hours
Total Biologics Burden 5,665,452.5
Hours
Total Human Drugs Burden 11,575,113
Hours
Total Combined Burdens 17,240,565.5
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Dated: August 6, 1999
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 99-20846 Filed 8-11-99; 8:45 am]
BILLING CODE 4160-01-F
