
[Federal Register Volume 76, Number 18 (Thursday, January 27, 2011)]
[Notices]
[Pages 4914-4917]
From the Federal Register Online via the Government Printing 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. 
Elizabeth.Berbakos@fda.hhs.gov.

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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           Annual frequency      Total annual
                   21 CFR section                    No. of respondents      per response          responses      Hours per response      Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
                                                    ----------------------------------------------------------------------------------------------------
    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
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
                                                   -----------------------------------------------------------------------------------------------------
    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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                           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
                                                    ----------------------------------------------------------------------------------------------------
    Total..........................................  ..................  ...................  ..................  ..................           4,350,287
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                         Number of        Annual frequency      Total annual
                  21 CFR Section                       recordkeepers     per recordkeeping         records         Hours per record       Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
                                                   -----------------------------------------------------------------------------------------------------
    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


