[Federal Register Volume 64, Number 87 (Thursday, May 6, 1999)]
[Notices]
[Pages 24402-24406]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11310]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 99N-1010]
Agency Information Collection Activities: Proposed Collection;
Comment Request; Investigational New Drug Regulations
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal agencies are required to publish a 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 governing
applications for FDA's approval to market a new drug.
DATES: Submit written comments on the collection of information by July
6, 1998.
ADDRESSES: Submit written comments on the collection of information to
the Dockets Management Branch (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: Karen Nelson, Office of Information
Resources Management (HFA-250), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-1482.
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 listed in this document.
With respect to the following collection of information, FDA
invites comments on: (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 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 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; 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.
The following two forms are required under part 312: Form FDA-1571
entitled ``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;
[[Page 24403]]
(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 entitled ``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
------------------------------------------------------------------------
21 CFR Section Explanations
------------------------------------------------------------------------
312.7(d)............................ Applications for permission to
sell an investigational new
drug.
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 (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), (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.
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 drug.
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.
[[Page 24404]]
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.
------------------------------------------------------------------------
Table 2.--Recordkeeping Requirements
------------------------------------------------------------------------
21 CFR Section Explanations
------------------------------------------------------------------------
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.
------------------------------------------------------------------------
Table 3.--Estimated Annual Reporting Burden for Human Drugs\1\
----------------------------------------------------------------------------------------------------------------
No. of
No. of Responses Total Annual Hours per
21 CFR Section Respondents Per Responses Response Total Hours
Respondent
----------------------------------------------------------------------------------------------------------------
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
[[Page 24405]]
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
----------------------------------------------------------------------------------------------------------------
\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\
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
\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\
----------------------------------------------------------------------------------------------------------------
No. of
21 CFR Section No. of Responses Total Annual Hours per Total Hours
Respondents Per Response Responses Response
----------------------------------------------------------------------------------------------------------------
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
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
----------------------------------------------------------------------------------------------------------------
\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\
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
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
[[Page 24406]]
312.160(a) 3,400 7.35 25,000 30 min 1,700
312.160(c) 320 1 320 0.5 160
Total Biologic 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
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Dated: April 29, 1999.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 99-11310 Filed 05-05-99; 8:45 am]
BILLING CODE 4160-01-F