[Federal Register Volume 76, Number 91 (Wednesday, May 11, 2011)]
[Notices]
[Pages 27328-27331]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-11540]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0042]


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 June 
10, 2011.

ADDRESSES: 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: FDA Desk Officer, 
FAX: 202-395-7285, or e-mailed to [email protected]. All 
comments should be identified with the OMB control number 0910-0014. 
Also include the FDA 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., 
PI50-400B, Rockville, MD 20850, 301-796-3792, 
[email protected].

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 (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 (the FD&C 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 FD&C 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 INDs.
    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; 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.
    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:

[[Page 27329]]

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.
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--Phases 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.

[[Page 27330]]

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.
    In the tables below, 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.
    In the Federal Register of January 27, 2011 (76 FR 4914), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                         Table 1--Estimated Annual Reporting Burden for Human Drugs \1\
----------------------------------------------------------------------------------------------------------------
                                                                                      Average
                                     Number of       Number of     Total annual     burden per
         21 CFR Section             respondents    responses per     responses     response  (in    Total hours
                                                    respondent                      hours) \2\
----------------------------------------------------------------------------------------------------------------
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                 45              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.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
  minutes per response]/60''.


                       Table 2--Estimated Annual Recordkeeping Burden for Human Drugs \1\
----------------------------------------------------------------------------------------------------------------
                                                                                      Average
                                     Number of       Number of     Total annual     burden per
         21 CFR Section            recordkeepers    records per       records      recordkeeping    Total hours
                                                   recordkeeper                   (in hours) \2\
----------------------------------------------------------------------------------------------------------------
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           30/60             383
312.160(c)......................             547            1.4              766           30/60             383
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............      10,123,452
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
  minutes per response]/60''.


[[Page 27331]]


                          Table 3--Estimated Annual Reporting Burden for Biologics \1\
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                                                                                      Average
                                    Number of       Number of      Total annual     burden per
         21 CFR Section            respondents    responses per      responses     response  (in    Total hours
                                                    respondent                      hours) \2\
----------------------------------------------------------------------------------------------------------------
312.7(d).......................              41              1.4              57              24           1,368
312.23(a) through (f) and                   433              1.3             563           1,808       1,017,904
 312.120(b), (c)(2), and (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                   647              2.3           1,488             360         535,680
 312.56(c).....................
312.35(a) and (b)..............               1              1                 1             300             300
312.36.........................               6              1                 6              16              96
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              18              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.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
  minutes per response]/60''.


                        Table 4--Estimated Annual Recordkeeping Burden for Biologics \1\
----------------------------------------------------------------------------------------------------------------
                                                                                      Average
                                     Number of       Number of     Total annual     burden per
         21 CFR Section            recordkeepers    records per       records      recordkeeping    Total hours
                                                   recordkeeper                   (in hours) \2\
----------------------------------------------------------------------------------------------------------------
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           30/60             102
312.160(c)......................             146            1.4              204           30/60             102
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............       2,563,994
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Burden estimates of less than 1 hour are expressed as a fraction of an hour in the format ``[number of
  minutes per response]/60''.


    Dated: May 6, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-11540 Filed 5-10-11; 8:45 am]
BILLING CODE 4160-01-P