
[Federal Register Volume 81, Number 138 (Tuesday, July 19, 2016)]
[Notices]
[Pages 46935-46938]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-17016]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0403]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Protection of Human Subjects: Informed Consent; 
Institutional Review Boards

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(the PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the collection of information 
related to certain regulations that provide protection for human 
subjects of clinical investigations conducted in support of 
applications or submissions to FDA for FDA-regulated products. The 
regulations provide protection of the rights, safety, and welfare of 
human subjects involved in research activities within FDA's 
jurisdiction.

DATES: Submit either electronic or written comments on the collection 
of information by September 19, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2013-N-0403 for ``Protection of Human Subjects; Informed Consent; 
Institutional Review Boards.'' Received comments will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at http://www.regulations.gov or at the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     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

[[Page 46936]]

for public viewing and posted on http://www.regulations.gov. Submit 
both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A63, 11601 
Landsdown St., North Bethesda, MD 20851, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
Agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes Agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal Agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

Protection of Human Subjects; Informed Consent; Institutional Review 
Boards--21 CFR Parts 50 and 56--OMB Control Number 0910-0755--Extension

    Part 50 (21 CFR part 50) applies to all clinical investigations 
regulated by FDA under sections 505(i) and 520(g) of the Federal Food, 
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 355(i) and 360j(g), 
respectively), as well as clinical investigations that support 
applications for research or marketing permits for products regulated 
by FDA, including foods and dietary supplements that bear a nutrient 
content claim or a health claim, infant formulas, food and color 
additives, drugs for human use, medical devices for human use, 
biological products for human use, and electronic products. Compliance 
with part 50 is intended to protect the rights and safety of subjects 
involved in investigations filed with FDA under sections 403, 406, 409, 
412, 413, 502, 503, 505, 510, 513-516, 518-520, 721, and 801 of the 
FD&C Act (21 U.S.C. 343, 346, 348, 350a, 350b, 352, 353, 355, 360, 
360c-360f, 360h-360j, 379e, and 381, respectively) and sections 351 and 
354-360F of the Public Health Service Act.
    With few exceptions, no investigator may involve a human being as a 
subject in FDA-regulated research unless the investigator has obtained 
the legally effective informed consent of the subject or the subject's 
legally authorized representative (see Sec.  50.20 (21 CFR 50.20)). In 
seeking informed consent, each subject must be provided with certain 
elements of informed consent. Those elements are listed in Sec.  50.25. 
Informed consent shall be documented in writing as described in Sec.  
50.27.
    An institutional review board (IRB) may approve emergency research 
without requiring the informed consent of all research subjects 
provided the IRB finds and documents that certain criteria are met as 
required in Sec.  50.24. We estimate that about eight times per year an 
IRB is requested to review emergency research under Sec.  50.24. We 
estimate, of the eight yearly requests for IRB review under Sec.  
50.24, a particular IRB will take about an hour during each of three 
separate fully convened IRB meetings to review the request under Sec.  
50.24 (one meeting occurring after community consultation). The total 
annual reporting burden for IRB review of emergency research under 
Sec.  50.24 is estimated at 24 hours (see table 1).
    The information requested in the regulations for exception from the 
general requirements for informed consent for medical devices (21 CFR 
812.47), and the information requested in the regulations for exception 
from the general requirements of informed consent in Sec.  50.23, 
paragraphs (a) through (c), and (e), is currently approved under OMB 
control number 0910-0586. The information requested in the 
investigational new drug (IND) regulations concerning exception from 
informed consent for emergency research under Sec.  50.24 is currently 
approved under OMB control number 0910-0014. In addition, the 
information requested in the regulations for IND safety reporting 
requirements for human drug and biological products and safety 
reporting requirements for bioavailability and bioequivalence studies 
in humans (21 CFR 320.31(d), and 21 CFR 312.32(c)(1)(ii) and (iv)) is 
currently approved under OMB control number 0910-0672.
    Some clinical investigations involving children, although otherwise 
not approvable, may present an opportunity to understand, prevent, or 
alleviate a serious problem affecting the health or welfare of children 
(see Sec.  50.54). Certain clinical investigations involving children 
may proceed if the IRB finds and documents that the clinical 
investigation presents a reasonable opportunity to further the 
understanding, prevention, or alleviation of a serious problem 
affecting the health or welfare of children and when the Commissioner 
of Food and Drugs, after consultation with a panel of experts in 
pertinent disciplines and following opportunity for public review and 
comment, makes a determination that certain conditions are met (see 
Sec.  50.54(b)).
    The information requested for clinical investigations in children 
of FDA-regulated products is covered by the collections of information 
in the IND regulations (part 312 (21 CFR part 312)), the 
investigational device exemption (IDE) regulations (part 812 (21 CFR 
part 812)), the IRB regulations (Sec.  56.115 (21 CFR 56.115)), the 
food additive petition and nutrient content claim petition regulations 
(21 CFR 101.69 and 101.70), and the infant formula regulations (parts 
106 and 107 (21 CFR parts 106 and 107)), all of which are approved by 
OMB. Specifically, the information

[[Page 46937]]

collected under the IND regulations is currently approved under OMB 
control number 0910-0014. The information collected under the IDE 
regulations is currently approved under OMB control number 0910-0078. 
The information collected under the IRB regulations is currently 
approved under OMB control number 0910-0130. The information collected 
in food additive and nutrient content claim petitions is currently 
approved under OMB control number 0910-0381 (general requirements) and 
0910-0016 (FDA Form 3503). The information collected under the infant 
formula regulations is currently approved under OMB control number 
0910-0256 (general requirements) and 0910-0188 (infant formula 
recalls).
    Part 56 (21 CFR part 56) contains the general standards for the 
composition, operation, and responsibility of an IRB that reviews 
clinical investigations regulated by FDA under sections 505(i) and 
520(g) of the FD&C Act, as well as clinical investigations that support 
applications for research or marketing permits for products regulated 
by FDA, including foods and dietary supplements that bear a nutrient 
content claim or a health claim, infant formulas, food and color 
additives, drugs for human use, medical devices for human use, 
biological products for human use, and electronic products. Compliance 
with part 56 is intended to protect the rights and welfare of human 
subjects involved in such investigations.
    The information collected under the IRB regulations ``Protection of 
Human Subjects--Recordkeeping and Reporting Requirements for 
Institutional Review Boards (part 56),'' including the information 
collection activities in the provisions in Sec.  56.108(a)(1) and (b), 
is currently approved under OMB control number 0910-0130. The 
information collected under the regulations for the registration of 
IRBs in Sec.  56.106 is currently approved under OMB control number 
0990-0279. The information collected for IRB review and approval for 
the IDE regulations (part 812) is currently approved under OMB control 
number 0910-0078. The information collected for premarket approval of 
medical devices (part 814 (21 CFR part 814)) is currently approved 
under OMB control number 0910-0231. The information collected under the 
regulations for IRB requirements for humanitarian use devices (part 
814, subpart H) is currently approved under OMB control number 0910-
0332. The information collected under the regulations for IRB review 
and approval of INDs (part 312) is currently approved under OMB control 
number 0910-0014.
    This collection of information is limited to certain provisions in 
part 50, subpart B (Informed Consent of Human Subjects), and part 56 
(Institutional Review Boards), currently approved under OMB control 
number 0910-0755.
    This proposed extension applies to the following collections of 
information in part 50: Sec. Sec.  50.24 (Exception from informed 
consent requirements for emergency research.), 50.25 (Elements of 
informed consent.), and 50.27 (Documentation of informed consent.).
    In part 56, this proposed extension applies to the following 
collections of information: Sec.  56.109(d) (written statement about 
research when documentation of informed consent is waived); Sec.  
56.109(e) (IRB written notification to approve or disapprove research); 
Sec.  56.109(f) (continuing review of research); Sec.  56.109(g) (IRB 
written statements to the sponsor about required public disclosures 
related to emergency research under Sec.  50.24); Sec.  56.113 
(Suspension or termination of IRB approval of research.); Sec.  
56.120(a) (IRB response to lesser administrative actions for 
noncompliance); and, Sec.  56.123 (Reinstatement of an IRB or an 
institution.).
    In Sec.  56.109(d), if an IRB has waived documentation of consent 
for research that (1) presents no more than minimal risk of harm to 
subjects and (2) involves no procedures for which consent is normally 
required outside of the research context, the IRB may nevertheless 
require the investigator to provide a written statement about the 
research to the subjects. We estimate that each IRB will review about 
two minimal risk FDA-regulated studies each year. Because the studies 
are minimal risk, the review can be fairly straightforward, and the 
written statement for the subjects would be brief. We estimate that IRB 
review of each written statement could be completed in less than 30 
minutes (0.5 hours).
    In Sec.  56.109(f), the amount of time an IRB spends on the 
continuing review of a particular study will vary depending on the 
nature and complexity of the research, the amount and type of new 
information presented to the IRB, and whether the investigator is 
seeking approval of substantive changes to the research protocol or 
informed consent document. For many studies, continuing review can be 
fairly straightforward, and the IRB should be able to complete its 
deliberations and approve the research within a brief period of time.
    In Sec.  56.109(g), an IRB is required to provide the sponsor of a 
study involving an exception from informed consent for emergency 
research under Sec.  50.24 with a written statement of information that 
has been publicly disclosed to the communities in which the 
investigation will be conducted and from which the subjects will be 
drawn. Public disclosure prior to initiation of the investigation would 
include the plans for the investigation and its risks and expected 
benefits. There must also be public disclosure of sufficient 
information following completion of the clinical investigation to 
apprise the community and researchers of the study, including the 
demographic characteristics of the research population, and its 
results. (See Sec.  50.24(a)(7)(ii) and (iii).) The purpose of the 
IRB's written statements is to make the sponsor aware that public 
disclosure has occurred, so that the sponsor can provide copies of the 
information that has been disclosed to FDA, as required by 21 CFR 
312.54(a) and 812.47(a).
    We estimate that about eight requests to review emergency research 
under Sec.  50.24 are submitted each year, and the IRBs that review 
those studies would prepare two public disclosure reports: One prior to 
initiation of the research and one following the study's completion. We 
estimate that it will take an IRB approximately 1 hour to prepare a 
written statement to the study sponsor describing each public 
disclosure, for a total of 2 hours per study. The total annual third 
party disclosure burden for IRBs to fulfill this requirement related to 
emergency research under Sec.  50.24 is estimated at 16 hours (see 
table 2).
    When an IRB or institution violates the regulations, FDA issues to 
the IRB or institution a noncompliance letter (see Sec.  56.120(a)). 
The IRB or institution must respond to the noncompliance letter 
describing the corrective actions that will be taken by the IRB or 
institution. FDA estimates about seven IRBs or institutions will be 
issued a noncompliance letter annually. We estimate that the IRB's or 
institution's response will take about 10 hours to prepare, with an 
estimated total annual burden of 70 hours.
    In 2016, FDA disqualified one IRB under Sec.  56.121. To date, no 
IRB or institution has been reinstated or applied for reinstatement 
under Sec.  56.123. For this reason, we estimate the annual reporting 
burden for one respondent only. We estimate a 5-hour burden per 
response, with an estimated total annual burden of 5 hours.
    The regulatory provisions in parts 50 and 56 currently approved 
under this collection of information, OMB control number 0910-0755, and 
for which this extension is requested, are shown in table 1.

[[Page 46938]]

    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of                        Average
         21 CFR Section              Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
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56.109(d) Written statement                2,520               2           5,040             0.5           2,520
 about minimal risk research                                                        (30 minutes)
 when documentation of informed
 consent is waived..............
56.109(e) IRB written                      2,520              40         100,800               1         100,800
 notification to approve or
 disapprove research; 56.109(f)
 Continuing review; 50.25
 Elements of informed consent;
 and 50.27 Documentation of
 informed consent...............
50.24 Exception from informed                  8               3              24               1              24
 consent requirements for
 emergency research.............
56.113 Suspension or termination           2,520               1           2,520             0.5           1,260
 of IRB approval of research....                                                    (30 minutes)
56.120(a) IRB response to lesser               7               1               7              10              70
 administrative actions for
 noncompliance..................
56.123 Reinstatement of an IRB                 1               1               1               5               5
 or an institution..............
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
    1Total......................  ..............  ..............  ..............  ..............         104,679
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                                               Table 2--Estimated Annual Third-Party Disclosure Burden \1\
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                                                                                         Number of
                           21 CFR Section                               Number of     disclosures per    Total annual   Average  burden    Total hours
                                                                       respondents       respondent      disclosures    per  disclosure
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56.109(g) IRB written statement about public disclosures to sponsor               8                2               16                1               16
 of emergency research under 50.24.................................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: July 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-17016 Filed 7-18-16; 8:45 am]
 BILLING CODE 4164-01-P


