[Federal Register Volume 86, Number 224 (Wednesday, November 24, 2021)]
[Notices]
[Pages 67060-67065]
[FR Doc No: 2021-25615]

=======================================================================
-----------------------------------------------------------------------

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

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,<PHONE_NUMBER>.
     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,<PHONE_NUMBER>.

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,<PHONE_NUMBER>,
[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

[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:

                          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.

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..................

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


[Federal Register Volume 78, Number 76 (Friday, April 19, 2013)]
[Rules and Regulations]
[Pages 23495-23497]
[FR Doc No: 2013-08948]

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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R05-OAR-2012-0073; FRL-9790-4]

Approval and Promulgation of Air Quality Implementation Plans;
Illinois; Small Container Exemption from VOC Coating Rules

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: EPA is approving a revision to the Illinois State
Implementation plan (SIP) submitted by the Illinois Environmental
Protection Agency (Illinois EPA) on November 14, 2011. This SIP
revision consists of amendments to the Illinois Administrative Code
(Ill. Adm. Code) by adding a ``small container exemption'' for pleasure
craft surface coating operations in the Chicago and Metro-East St.
Louis 8-hour ozone nonattainment areas. These exemptions are approvable
because they are consistent with EPA volatile organic compound (VOC)
reasonably available control technology (RACT) policy.

DATES: This final rule is effective on May 20, 2013.

ADDRESSES: EPA has established a docket for this action under Docket ID
No. EPA-R05-OAR-2012-0073. All documents in the docket are listed on
the www.regulations.gov Web site. Although listed in the index, some
information may not be publicly available, i.e., Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. Certain other material, such as copyrighted material, is
not placed on the Internet and will be publicly available only in hard
copy form. Publicly available docket materials are available either
electronically through www.regulations.gov or in hard copy at the
Environmental Protection Agency, Region 5, Air and Radiation Division,
77 West Jackson Boulevard, Chicago, Illinois 60604. This facility is
open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding
Federal holidays. We recommend that you telephone Steven Rosenthal,
Environmental Engineer, at<PHONE_NUMBER> before visiting the Region 5
office.

FOR FURTHER INFORMATION CONTACT: Steven Rosenthal, Environmental
Engineer, Attainment Planning and Maintenance Section, Air Programs
Branch (AR-18J), Environmental Protection Agency, Region 5, 77 West
Jackson Boulevard, Chicago, Illinois 60604,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: Throughout this document whenever ``we,''
``us,'' or ``our'' is used, we mean EPA. This supplementary information
section is arranged as follows:

I. What public comments were received on the proposed approval and
what is EPA's response?
II. What action is EPA taking today?
III. Statutory and Executive Order Reviews

I. What public comments were received on the proposed approval and what
is EPA's response?

    A comment was submitted on April 16, 2012, by a Kentucky resident.
As a result of this comment, the direct final approval published on
April 16, 2012, (77 FR 22497) was withdrawn. His comment is that EPA
should determine, pursuant to Clean Air Act (CAA) section 110(l), what
impact this exemption will have on St. Louis and Chicago attaining the
2008 National Ambient Air Quality Standard (NAAQS) as soon as

practicable before EPA can approve this revision.

EPA Response

    As stated in the direct final approval, and included here as
background to EPA's response, EPA previously approved sections
218.208(c) and 219.208(c) which specify that Illinois' surface coating
VOC emission limitations shall not apply to touch-up and repair
coatings used by a can, coil, vinyl, metal furniture and magnet wire
coating operation, provided that the source-wide volume of such
coatings used does not exceed 1 quart per 8-hour period or exceed 55
gallons/year for any rolling 12 month period. (61 FR 5511 on February
13, 1996). The SIP revision which is the subject of this action extends
the exemption in 218.208(c) and 219.208(c) to the pleasure craft
surface coating limits set out in sections 218.204(q)(5) and
219.204(q)(5). Illinois' SIP revision also amends 35 Ill. Adm. Code
218.208(e) and 219.208(e), the recordkeeping and reporting provisions,
to add pleasure craft coating operations that are exempted from the
limitations in 218.204(q) and 219.204(q) to the coating operations
subject to recordkeeping requirements. Sections 218.208(e) and
219.208(e) contain sufficient recordkeeping requirements to establish
whether these exemptions have been exceeded.
    In 2010 and 2011 Illinois promulgated rules on VOC RACT emission
limitations for coating operations (See November 30, 2011 proposed
approval at 76 FR 74014). During that rulemaking, the American Coatings
Association (ACA) commented to Illinois EPA that many VOC coating
regulations include a small container exemption not to exceed a liter
or a quart. The ACA stated that the basis for these exemptions is to
allow for small repairs and touch ups to existing coatings at the end
of the painting line to avoid having to completely recoat the product,
thus resulting in lower VOC emissions overall from pleasure craft
coating operations.
    In direct response to the comment, EPA has determined that this
exemption will not interfere with St. Louis and Chicago attaining the
2008 ozone NAAQS for the following reasons:
    (1) Illinois EPA is not aware of any subject sources in the Chicago
and Metro East (St. Louis) 2008 ozone nonattainment areas.
    (2) One quart of touch up coating per day (55 gallons per year) is
a de minimis amount.
    (3) The exemption is consistent with Illinois RACT rules for
similar coating operations, including can, coil, vinyl, metal
furniture, and magnet wire coatings.
    (4) Illinois EPA and ACA agree that the exemption may reduce VOC
emissions by encouraging repairs and touch ups, as opposed to
performing complete re-coats.

II. What action is EPA taking

    EPA is approving the State's request to add a ``small container
exemption'' for pleasure craft surface coating operations in the
Chicago and Metro-East St. Louis 8-hour ozone nonattainment areas for
the reasons stated above.

III. Statutory and Executive Order Reviews

    Under the CAA, the Administrator is required to approve a SIP
submission that complies with the provisions of the CAA and applicable
Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in
reviewing SIP submissions, EPA's role is to approve state choices,
provided that they meet the criteria of the CAA. Accordingly, this
action merely approves state law as meeting Federal requirements and
does not impose additional requirements beyond those imposed by state
law. For that reason, this action:
     Is not a ``significant regulatory action'' subject to
review by the Office of Management and Budget under Executive Order
12866 (58 FR 51735, October 4, 1993);
     does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the CAA; and
     does not provide EPA with the discretionary authority to
address, as appropriate, disproportionate human health or environmental
effects, using practicable and legally permissible methods, under
Executive Order 12898 (59 FR 7629, February 16, 1994).
    In addition, this rule does not have tribal implications as
specified by Executive Order 13175 (65 FR 67249, November 9, 2000),
because the SIP is not approved to apply in Indian country located in
the state, and EPA notes that it will not impose substantial direct
costs on tribal governments or preempt tribal law.
    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this action and
other required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the CAA, petitions for judicial review
of this action must be filed in the United States Court of Appeals for
the appropriate circuit by June 18, 2013. Filing a petition for
reconsideration by the Administrator of this final rule does not affect
the finality of this action for the purposes of judicial review nor
does it extend the time within which a petition for judicial review may
be filed, and shall not postpone the effectiveness of such rule or
action. This action may not be challenged later in proceedings to
enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Intergovernmental relations, Volatile organic compounds.

    Dated: March 4, 2013.
Susan Hedman,
Regional Administrator, Region 5.

    40 CFR part 52 is amended as follows:

PART 52--[AMENDED]

0
1. The authority citation for part 52 continues to read as follows:

    Authority: 42 U.S.C. 7401 et seq.

0
2. Sec.  52.720 is amended by adding paragraph (c)(194) to read as
follows:

Sec.  52.720  Identification of plan.

* * * * *
    (c) * * *
    (194) On November 14, 2011, the Illinois Environmental Protection
Agency (Illinois EPA) submitted amendments to 35 Illinois
Administrative Code 218.208 and 219.208. These sections add a ``small
container exemption'' for pleasure craft surface coating operations in
the Chicago and Metro-East St. Louis 8-hour ozone nonattainment areas.
These exemptions are consistent with EPA volatile organic compound
(VOC) reasonably available control technology (RACT) policy.
    (i) Incorporation by reference. The following sections of Illinois
Administrative Code, Title 35: Environmental Protection, Subtitle B:
Air Pollution, Chapter 1: Pollution Control Board, Subchapter c:
Emission Standards and Limitations for Stationary Sources, are
incorporated by reference.
    (A) Part 218: Organic Material Emission Standards and Limitations
for the Chicago Area, Subpart F: Coating Operations, Section 218.208
Exemptions From Emission Limitations; effective October 25, 2011.
    (B) Part 219: Organic Material Emission Standards and Limitations
for the Metro East Area, Subpart F: Coating Operations, Section 219.208
Exemptions From Emission Limitations; effective October 25, 2011.

[FR Doc. 2013-08948 Filed 4-18-13; 8:45 am]
BILLING CODE 6560-50-P