Document ID: FDA-2014-N-1721-0016
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection; Comment Request; Investigational New Drug Application Requirements
Posted Date: 2021-11-24T05:00Z

[Federal Register Volume 86, Number 224 (Wednesday, November 24, 2021)]
[Notices]
[Pages 67060-67065]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-25615]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-1721]

Agency Information Collection Activities; Proposed Collection; 
Comment Request; Investigational New Drug Application Requirements

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
announcing an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (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 information collection 
associated with investigational new drug application requirements.

DATES: Submit either electronic or written comments on the collection 
of information by January 24, 2022.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before January 24, 2022. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of January 24, 2022. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and

[[Page 67061]]

identified, as confidential, if submitted as detailed in 
``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2014-N-1721 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Investigational New Drug 
Applications.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
[email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), 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 Applications--21 CFR Part 312

OMB Control Number 0910-0014--Revision

    This information collection supports implementation of provisions 
of section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) 
(21 U.S.C. 355) and of the licensing provisions of the Public Health 
Service Act (42 U.S.C. 201 et seq.) that govern investigational new 
drugs and investigational new drug applications (INDs). Implementing 
regulations are found in part 312 (21 CFR part 312), and provide for 
the issuance of guidance documents (see Sec.  312.145 (21 CFR 312.145)) 
to assist persons in complying with the applicable requirements. The 
information collection applies to all clinical investigations subject 
to section 505 of the FD&C Act and include the following types of INDs:
     An Investigator IND is submitted by a physician who both 
initiates and investigates, and under whose immediate direction the 
investigational drug is administered or dispensed. A physician might 
submit a research IND to propose studying an unapproved drug or an 
approved product for a new indication or in a new patient population.
     Emergency Use IND allows FDA to authorize use of an 
experimental drug in an emergency situation that does not allow time 
for submission of an IND in accordance with Sec.  312.23 or Sec.  
312.20 (21 CFR 312.23 or 312.20). It is also used for patients who do 
not meet the criteria of an existing study protocol or if an approved 
study protocol does not exist.
     Treatment IND is submitted for experimental drugs showing 
promise in clinical testing for serious or immediately life-threatening 
conditions while the final clinical work is conducted and FDA's review 
takes place.
    There are two IND categories: Commercial and research (non-
commercial).
    General IND requirements include submitting an initial application 
as well as amendments to that application; submitting reports on 
significant revisions of clinical investigation plans; submitting 
information to the clinical trials data bank (https://clinicaltrials.gov) established by the National Institutes of Health/
National Library of Medicine, including expanded information on certain 
clinical trials and information on the results of these clinical 
trials; and reporting information on a drug's safety or effectiveness. 
In addition, sponsors are required to provide to FDA an annual summary 
of the previous year's clinical experience. The regulations also 
include recordkeeping requirements regarding the disposition of drugs, 
records regarding individual case histories, and certain other 
documentation verifying clinical investigators' fulfillment of 
responsibilities.
    Form FDA 1571 entitled ``Investigational New Drug Application 
(IND)'' and Form FDA 1572 entitled ``Statement of Investigator,'' were 
developed to assist respondents with the information collection and 
provide for uniform reporting of required data elements. The 
information is required to be submitted electronically. Individuals who 
are interested in receiving printed forms may send an email request to 
the FDA Forms Manager at

[[Page 67062]]

[email protected] Fees may apply. Sponsors (including sponsor-
investigators) interested in filing or updating a research IND may use 
a new web-based interface developed for use by mobile device or desktop 
to help in completing Form FDA 1571. The web-based interface also 
allows respondents to electronically submit completed Form FDA 1571 and 
associated files. For more information regarding Forms FDA 1571 and 
1572 visit https://www.fda.gov/news-events/expanded-access/how-complete-form-fda-1571-and-form-fda-1572.
    Human drug, biological product, and device product submissions must 
be accompanied by Form FDA 3674, ``Certification To Accompany Drug, 
Biological Product, and Device Applications or Submissions.'' The 
guidance document ``Form FDA 3674--Certifications To Accompany Drug, 
Biological Product, and Device Application'' (November 2017) is 
available from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/form-fda-3674-certifications-accompany-drug-biological-product-and-device-applicationssubmissions 
and provides instruction on completing and submitting this information 
to FDA. As communicated in the instructions, the certification must 
accompany the application or submission and be included at the time of 
submission to FDA.
    Regulations in part 312, subpart B, specify content and format 
requirements for applications, amendments, annual reporting, and 
withdrawals, including content and format requirements for protocol and 
information amendments. The regulations also explain phases of an 
investigation and set forth principles of IND submissions.
    Regulations in part 312, subpart C, describe administrative actions 
pertaining to respondents' requests for and responses to clinical 
holds, terminations, and inactive IND status determinations, as well as 
various types of meetings (for example, End-of-Phase 2 and Pre-new drug 
application (NDA) meetings).
    Regulations in part 312, subpart D, set forth sponsor and 
investigator responsibilities, including general responsibilities; 
transfer of obligations to a contract research organization; 
recordkeeping and record retention controls; reporting 
responsibilities; and responsibility for disposition of unused supply 
of investigational drug. The regulations also provide for investigator 
controls including review of ongoing investigations; compliance with 
requirements regarding the protection of human subjects and 
institutional review board assurance; and disqualification of clinical 
investigators.
    Regulations in part 312, subpart E, sets forth requirements 
applicable to drugs intended to treat life-threatening and severely 
debilitating illnesses. The regulations establish procedures to reflect 
that physicians and patients accept greater risk or side effects from 
products that treat life-threatening and severely debilitating 
illnesses than they would accept from products that treat less serious 
illnesses. The procedures also reflect the recognition that the 
benefits of the drug need to be evaluated in light of the severity of 
the disease being treated.
    Regulations in part 312, subpart F, include provisions pertaining 
to import and export requirements; foreign clinical studies not 
conducted under an IND; the disclosure of data and information in an 
IND; and the issuance of guidance documents. We are revising the 
information collection to account for burden that may be associated 
with recommendations found in Agency guidance documents.
     The guidance document entitled ``Oversight of Clinical 
Investigations'' (August 2013) communicates risk-based monitoring 
strategies and recommends plans for investigational studies of medical 
products, including human drug and biological products, medical 
devices, and combinations thereof. The guidance document is intended to 
enhance human subject protection and the quality of clinical trial data 
by focusing sponsor oversight on the most important aspects of study 
conduct and reporting. The guidance also communicates that sponsors can 
use a variety of approaches to fulfill responsibilities for monitoring 
clinical investigator conduct and performance in IND studies, and 
provides a description of strategies for monitoring activities to 
reflect a modern, risk-based approach.
     The guidance document entitled ``Pharmacogenomic Data 
Submissions'' (March 2005) provides recommendations intended to assist 
sponsors submitting or holding INDs, NDAs, or biologics license 
applications (BLAs) with submission requirements for relevant data 
regarding drug safety and effectiveness (including Sec. Sec.  312.22, 
312.23, 312.31, 312.33, 314.50, 314.81, 601.2, and 601.12 (21 CFR 
312.22, 312.23, 312.31, 312.33, 314.50, 314.81, 601.2 and 601.12)). 
Because the regulations were developed before the advent of widespread 
animal or human genetic or gene expression testing, the regulations do 
not specifically address when such data must be submitted. The guidance 
document includes content and format recommendations regarding 
pharmacogenomic data submissions. Although we have not received any 
pharmacogenomic submissions since 2013, we assume an average of 50 
hours for preparing and providing information to FDA as recommended in 
the guidance and estimate one submission annually.
     The guidance document entitled ``Adaptive Designs for 
Clinical Trials of Drugs and Biologics'' (December 2019) was developed 
to assist sponsors and applicants submitting INDs, NDAs, BLAs, or 
supplemental applications on the appropriate use of adaptive designs 
for clinical trials to provide evidence of the effectiveness and safety 
of a drug or biologic. The guidance document describes important 
principles for designing, conducting, and reporting the results from an 
adaptive clinical trial, and advises sponsors on the types of 
information to submit to facilitate FDA evaluation of clinical trials 
with adaptive designs, including Bayesian adaptive and complex trials 
that rely on computer simulations for their design.
    The referenced guidance documents are available for download from 
our website at https://www.fda.gov/regulatory-information/search-fda-guidance-document and were issued consistent with Sec.  312.145 to help 
respondents comply with requirements in part 312. In publishing the 
respective notices of availability for each guidance document, we 
included an analysis under the PRA and invited public comment on the 
associated information collection recommendations. In addition, all 
Agency guidance documents are issued in accordance with our Good 
Guidance Practice regulations in 21 CFR 10.115, which provide for 
public comment at any time.
    Regulations in part 312, subpart G, provide for drugs for 
investigational use in laboratory research animals or in vitro tests.
    We estimate the burden of this collection of information as 
follows:

[[Page 67063]]

                          Table 1--Estimated Annual Reporting Burden for Biologics \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
   21 CFR section; information       Number of     responses per   Total annual   Average burden    Total hours
       collection activity          respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
                        Subpart A--General Provisions: Sec.  Sec.   312.1 through 312.10
----------------------------------------------------------------------------------------------------------------
Sec.   312.2(e); requests for                454           1.528             694              24          16,656
 FDA advice on the applicability
 of part 312 to a planned
 clinical investigation.........
Sec.   312.8; requests to charge              14            1.64              23              48           1,104
 for an investigational drug....
Sec.   312.10; waiver requests..               5               1               5              24             120
                                 -------------------------------------------------------------------------------
    Subtotal Subpart A Center     ..............  ..............             722  ..............          17,880
     for Biologics Evaluation
     and Research (CBER)........
----------------------------------------------------------------------------------------------------------------
 Subpart B--Investigational New Drug Application (IND): Sec.  Sec.   312.20 through 312.38 (Including Forms FDA
                                              1571, 1572, and 3674)
----------------------------------------------------------------------------------------------------------------
Sec.   312.23(a) through (f);              2,075           3.382           7,018             300       2,105,400
 IND content and format.........
Sec.   312.30(a) through (e);              1,781          4.6692           8,316             284       2,361,744
 Protocol amendments............
Sec.   312.31(b); information                169            2.48             419             100          41,900
 amendments.....................
Sec.   312.32(c) and (d); IND                224           10.59           2,372              32          75,904
 Safety reports.................
Sec.   312.33(a) through (f);                971          2.2739           2,208             360         794,880
 IND Annual reports.............
Sec.   312.38(b) and (c);                    712           3.057           2,177              28          60,956
 notifications of withdrawal of
 an IND.........................
                                 -------------------------------------------------------------------------------
    Subtotal Subpart B CBER.....  ..............  ..............          22,510  ..............       5,440,784
----------------------------------------------------------------------------------------------------------------
                      Subpart C--Administrative Actions: Sec.  Sec.   312.40 through 312.48
----------------------------------------------------------------------------------------------------------------
Sec.   312.42; clinical holds                154            1.65             254             284          72,136
 and requests for modification..
Sec.   312.44(c) and (d);                     86            1.22             105              16           1,680
 sponsor responses to FDA when
 IND is terminated..............
Sec.   312.45(a) and (b);                     48            1.48              71              12             852
 sponsor requests for or
 responses to an inactive status
 determination of an IND by FDA.
Sec.   312.47; meetings,                     157            1.80             283             160          45,280
 including ``End-of-Phase 2''
 meetings and ``Pre-NDA''
 meetings.......................
                                 -------------------------------------------------------------------------------
    Subtotal Subpart C CBER.....  ..............  ..............             713  ..............         119,948
----------------------------------------------------------------------------------------------------------------
          Subpart D--Responsibilities of Sponsors and Investigators: Sec.  Sec.   312.50 through 312.70
----------------------------------------------------------------------------------------------------------------
Sec.   312.53(c); investigator             1,068            5.23           5,586              80         446,880
 reports submitted to the
 sponsor, including Form FDA-
 1572, curriculum vitae,
 clinical protocol, and
 financial disclosure...........
Sec.   312.54(a); sponsor                      4            4.25              17              48             816
 submissions to FDA concerning
 investigations involving an
 exception from informed consent
 under Sec.   50.24.............
Sec.   312.54(b); sponsor                      1               1               1              48              48
 notifications to FDA and others
 concerning an institutional
 review board determination that
 it cannot approve research
 because it does not meet the
 criteria in the exception from
 informed consent in Sec.
 50.24(a).......................
Sec.   312.55(a); number of                  473           2.224           1,052              48          50,496
 investigator brochures
 submitted by the sponsor to
 each investigator..............
Sec.   312.55(b); number of                  243            4.95           1,203              48          57,744
 sponsor reports to
 investigators on new
 observations, especially
 adverse reactions and safe use.
Sec.   312.56(b), (c), and (d);              915           2.948           2,698              80         215,840
 review of ongoing
 investigations and associated
 notifications; sponsor
 notifications..................
Sec.   312.58; inspection of                   7               1               7               8              56
 records and reports by FDA.....
Sec.   312.64; number of                   2,728           3.816          10,411              24         249,864
 investigator reports to the
 sponsor, including progress
 reports, safety reports, final
 reports, and financial
 disclosure reports.............
Sec.   312.70; disqualification                5               1               5              40             200
 of a clinical investigator by
 FDA............................
                                 -------------------------------------------------------------------------------
    Subtotal Subpart D CBER.....  ..............  ..............          20,980  ..............       1,021,944
----------------------------------------------------------------------------------------------------------------
                         Subpart F--Miscellaneous: Sec.  Sec.   312.110 through 312.145
----------------------------------------------------------------------------------------------------------------
Sec.   312.110(b)(4) and (b)(5);              18               1              18              75           1,350
 number of written
 certifications and written
 statements submitted to FDA
 relating to the export of an
 investigational drug...........
Sec.   312.120(b); number of                 280            9.82           2,750              32          88,000
 submissions to FDA of
 ``supporting information''
 related to the use of foreign
 clinical studies not conducted
 under an IND...................
Sec.   312.120(c); number of                   7            2.29              16              24             384
 waiver requests submitted to
 FDA related to the use of
 foreign clinical studies not
 conducted under an IND.........
Sec.   312.130; number of                    350           1.342             470               8           3,760
 requests for disclosable
 information in an IND and for
 investigations involving an
 exception from informed consent
 under Sec.   50.24.............
                                 -------------------------------------------------------------------------------
    Subtotal Subpart F CBER.....  ..............  ..............           3,254  ..............          93,494
                                 -------------------------------------------------------------------------------
        Total...................  ..............  ..............          48,179  ..............       6,694,050
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

                                            Table 2--Estimated Annual Recordkeeping Burden for Biologics \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Number of
    21 CFR section; information collection        Number of       records per    Total annual       Average burden per recordkeeping        Total hours
                   activity                     recordkeepers    recordkeeper       records
--------------------------------------------------------------------------------------------------------------------------------------------------------
                              Subpart D--Responsibilities of Sponsors and Investigators: Sec.  Sec.   312.50 Through 312.70
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   312.52(a); sponsor records for the                   94            2.26             212  2.......................................             424
 transfer of obligations to a contract
 research organization.

[[Page 67064]]

 
Sec.   312.57; sponsor recordkeeping showing               335            2.70             904  100.....................................          90,400
 the receipt, shipment, or other disposition
 of the investigational drug, and any
 financial interest.
Sec.   312.62(a); investigator recordkeeping               453               1             453  40......................................          18,120
 of the disposition of drugs.
Sec.   312.62(b); investigator recordkeeping               453               1             453  40......................................          18,120
 of case histories of individuals.
                                              ----------------------------------------------------------------------------------------------------------
    Subtotal Subpart D CBER..................  ...............  ..............           2,022  ........................................         127,064
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                Subpart G--Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   312.160(a)(3); records pertaining to                111            1.40             155  0.5 (30 minutes)........................              78
 the shipment of drugs for investigational
 use in laboratory research animals or in
 vitro tests.
Sec.   312.160(c) shipper records of                       111            1.40             155  0.5 (30 minutes)........................              78
 alternative disposition of unused drugs.
                                              ----------------------------------------------------------------------------------------------------------
    Subtotal Subpart G CBER..................  ...............  ..............             310  ........................................             156
                                              ----------------------------------------------------------------------------------------------------------
        Total................................  ...............  ..............           2,332  ........................................         127,220
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                         Table 3--Estimated Annual Reporting Burden for Human Drugs \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
  21 CFR section; information       Number of      responses per   Total annual   Average burden    Total hours
      collection activity          respondents      respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
                                          Subpart A--General Provisions
----------------------------------------------------------------------------------------------------------------
Sec.   312.2(e); requests for                419               1             419              24          10,056
 FDA advice on the
 applicability of part 312 to a
 planned clinical investigation
Sec.   312.8; requests to                     25            1.28              32              48           1,536
 charge for an investigational
 drug..........................
Sec.   312.10; requests to                    68             1.5             102              24           2,448
 waive a requirement in part
 312...........................
                                --------------------------------------------------------------------------------
    Subtotal Subpart A Center    ...............  ..............             553  ..............          14,040
     for Drug Evaluation and
     Research (CDER)...........
----------------------------------------------------------------------------------------------------------------
                              Subpart B--Investigational New Drug Application (IND)
----------------------------------------------------------------------------------------------------------------
Sec.   312.23(a) through (f);              4,886          1.4662           7,164             300       2,149,200
 IND content and format
 (including Forms FDA 1571 and
 3674).........................
Sec.   312.30(a) through (e);             11,847          3.2367          38,346          284.25      10,899,850
 protocol amendments...........
Sec.   312.31(b); Information              8,094         3.30899          26,783             100       2,678,300
 amendments....................
Sec.   312.32(c) and (d); IND                892          15.848          14,137              32         452,384
 safety reports................
Sec.   312.33(a) through (f);              3,777          2.9097          10,990             360       3,956,400
 IND annual reports............
Sec.   312.38(b) and (c);                  1,549           1.834           2,841              28          79,548
 notifications of withdrawal of
 an IND........................
                                --------------------------------------------------------------------------------
    Subtotal Subpart B CDER....  ...............  ..............         100,261  ..............      20,215,682
----------------------------------------------------------------------------------------------------------------
                      Subpart C--Administrative Actions: Sec.  Sec.   312.40 through 312.48
----------------------------------------------------------------------------------------------------------------
Sec.   312.42; clinical holds                181            1.28             232             284          65,888
 and requests for modifications
Sec.   312.44(c) and (d);                      1               1               1              16              16
 sponsor responses to FDA when
 IND is terminated.............
Sec.   312.45(a) and (b);                    213            1.72             367              12           4,404
 sponsor requests for or
 responses to an inactive
 status determination of an IND
 by FDA........................
Sec.   312.47; meetings,                     174           2.885             502             160          80,320
 including ``End-of-Phase 2''
 meetings and ``Pre-NDA''
 meetings......................
                                --------------------------------------------------------------------------------
    Subtotal Subpart C CDER....  ...............  ..............           1,102  ..............         150,628
----------------------------------------------------------------------------------------------------------------
                            Subpart D--Responsibilities of Sponsors and Investigators
----------------------------------------------------------------------------------------------------------------
Sec.   312.54(a); sponsor                      7            1.14               8              48             384
 submissions to FDA concerning
 investigations involving an
 exception from informed
 consent under Sec.   50.24....
Sec.   312.54(b); sponsor                      2               1               2              48              96
 notifications to FDA and
 others concerning an
 institutional review board
 determination that it cannot
 approve research because it
 does not meet the criteria in
 the exception from informed
 consent in Sec.   50.24(a)....
Sec.   312.56; review of                   4,570          5.4689          24,993              80       1,999,440
 ongoing investigations and
 associated notifications......
Sec.   312.58; inspection of                  73               1              73               8             584
 records and reports by FDA....
Sec.   312.70; disqualification                5               1               5              40             200
 of a clinical investigator by
 FDA...........................
                                --------------------------------------------------------------------------------
    Subtotal Subpart D CDER....  ...............  ..............          25,081  ..............       2,000,704
----------------------------------------------------------------------------------------------------------------
                         Subpart F--Miscellaneous: Sec.  Sec.   312.110 through 312.145
----------------------------------------------------------------------------------------------------------------
Sec.   312.110(b)(4) and                       8          22.375             179              75          13,425
 (b)(5); written certifications
 and written statements
 submitted to FDA relating to
 the export of an
 investigational drug..........
Sec.   312.120(b); submissions             1,964           7.352          14,440              32         462,080
 to FDA of ``supporting
 information'' related to the
 use of foreign clinical
 studies not conducted under an
 IND...........................
Sec.   312.120(c); waiver                     68             1.5             102              24           2,448
 requests submitted to FDA
 related to the use of foreign
 clinical studies not conducted
 under an IND..................

[[Page 67065]]

 
Sec.   312.130; requests for                   3               1               3               8              24
 disclosable information in an
 IND and for investigations
 involving an exception from
 informed consent under Sec.
 50.24.........................
Sec.   312.145; Guidance
 Documents:
Oversight of Clinical                         88             1.5             132               4             528
 Investigations (2013).........
Pharmacogenomic Data                           1               1               1              50              50
 Submissions (2005)............
Adaptive Designs for Clinical                 55           4.727             260              50          13,000
 Trials of Drugs and Biologics
 (2019)........................
                                --------------------------------------------------------------------------------
    Subtotal Subpart F CDER....  ...............  ..............          15,117  ..............         491,555
                                --------------------------------------------------------------------------------
        Total..................  ...............  ..............         142,114  ..............      22,872,609
----------------------------------------------------------------------------------------------------------------
\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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                   Number of
    21 CFR section; information collection        Number of       records per    Total annual       Average burden per recordkeeping        Total hours
                   activity                     recordkeepers    recordkeeper       records
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                Subpart D--Responsibilities of Sponsors and Investigators
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   312.52(a); transfer of obligations to               466           3.107           1,448  300.....................................         434,400
 a contract research organization.
Sec.   312.57; records showing the receipt,             13,000               1          13,000  100.....................................       1,300,000
 shipment, or other disposition of the
 investigational drug and any financial
 interests.
Sec.   312.62(a); records on disposition of             13,000               1          13,000  40......................................         520,000
 drugs.
Sec.   312.62(b); records on case histories              2,192           6.587          14,439  40......................................         577,560
 of individuals.
                                              ----------------------------------------------------------------------------------------------------------
    Subtotal Subpart D CDER..................  ...............  ..............          41,887  ........................................       2,831,960
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                                Subpart G--Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   312.160(a)(3); records pertaining to                547            1.43             782  0.50 (30 minutes).......................             391
 the shipment of drugs for investigational
 use in laboratory research animals or in
 vitro tests.
Sec.   312.160(c); shipper records of                      547            1.43             782  0.50 (30 minutes).......................             391
 alternative disposition of unused drugs.
    Subtotal.................................  ...............  ..............           1,564  ........................................             782
                                              ----------------------------------------------------------------------------------------------------------
        Total................................  ...............  ..............          43,451  ........................................       2,832,742
--------------------------------------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    The information collection reflects program changes and 
adjustments. We have revised the information collection to account for 
burden that may be incurred by respondents who choose to adopt or 
implement recommendations discussed in referenced Agency guidance 
documents intended to assist respondents in complying with regulatory 
requirements in part 312. We have also made adjustments to individual 
collection elements. As a result of these changes and adjustments, the 
information collection reflects an overall decrease in both annual 
responses and burden hours. Finally, we have removed burden we 
attribute to provisions in part 312, subpart I: Expanded Access to 
Investigational Drugs for Treatment Use and are revising OMB control 
number 0910-0814 to include burden associated with information 
collection applicable to these regulatory provisions for efficiency of 
Agency operations.

    Dated: November 17, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-25615 Filed 11-23-21; 8:45 am]
BILLING CODE 4164-01-P