[Federal Register Volume 88, Number 62 (Friday, March 31, 2023)]
[Notices]
[Pages 19310-19312]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-06649]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0142]


Research Involving Children as Subjects and Not Otherwise 
Approvable by an Institutional Review Board: Process for Referrals to 
Food and Drug Administration and Office for Human Research Protections, 
Guidance for Institutional Review Boards, Investigators, and Sponsors; 
Draft Guidance for Industry; Availability; Agency Information 
Collection Activities; Proposed Collection; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Research 
Involving Children as Subjects and Not Otherwise Approvable by an IRB: 
Process for Referrals to FDA and OHRP.'' This guidance is intended to 
assist institutional review boards (IRBs), institutions, investigators, 
and sponsors in understanding the processes used for review of research 
involving children as subjects that is not otherwise approvable by an 
IRB and has been referred to FDA, the Office for Human Research 
Protections (OHRP), or both, for review. When final, this guidance will 
replace the final guidance issued by FDA in December 2006 entitled, 
``Guidance for Clinical Investigators, Institutional Review Boards and 
Sponsors: Process for Handing Referrals to FDA Under 21 CFR 50.54: 
Additional Safeguards for Children in Clinical Investigations'' and the 
guidance issued by the OHRP entitled ``Children as Research Subjects 
and the HHS `407' Process,'' issued on May 26, 2005. This draft 
guidance is not final nor is it in effect at this time.

DATES: Submit either electronic or written comments on the draft 
guidance by May 30, 2023 to ensure that the Agency and OHRP consider 
your comment on this draft guidance before they begin work on the final 
version of the guidance. Submit electronic or written comments on the 
proposed collection of information in the draft guidance by May 30, 
2023.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

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-2022-D-0142 for ``Research Involving Children as Subjects and Not 
Otherwise Approvable by an IRB: Process for Referrals to FDA and OHRP, 
Guidance for Institutional Review Boards, Investigators, and 
Sponsors.'' Received comments 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

[[Page 19311]]

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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this draft guidance to 
the Office of Pediatric Therapeutics, Office of the Commissioner, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5126, 
Silver Spring, MD 20993-0002; or Office for Human Research Protections, 
Division of Policy and Assurances, 1101 Wootton Pkwy., Suite 200, 
Rockville, MD 20852. Send one self-addressed adhesive label to assist 
that office in processing your request or include a Fax number to which 
the draft guidance may be sent. See the SUPPLEMENTARY INFORMATION 
section for information on electronic access to the draft guidance.

FOR FURTHER INFORMATION CONTACT: 
    With regard to the draft guidance: Donna Snyder, Office of 
Pediatric Therapeutics, Office of the Commissioner, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5121, Silver 
Spring, MD 20993-0002, 301-796-1397, [email protected]; or 
Natalie Klein, Office for Human Research Protections, 1101 Wootton 
Pkwy., Suite 200, Rockville, MD 20852, 240-453-6900 or toll free within 
the United States, 866-447-4777, [email protected].
    With regard to the proposed collection of information: 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:

I. Background

    FDA and the OHRP are announcing the availability of a draft 
guidance for IRBs, institutions, investigators, and sponsors entitled 
``Research Involving Children as Subjects and Not Otherwise Approvable 
by an IRB: Process for Referrals to FDA and OHRP, Guidance for 
Institutional Review Boards, Investigators, and Sponsors.'' This 
guidance is intended to assist IRBs, institutions, investigators, and 
sponsors in understanding the processes for review of research 
involving children as subjects that is not otherwise approvable by an 
IRB and has been referred to FDA under Sec.  50.54 (21 CFR 50.54), OHRP 
under 45 CFR 46.407, or both, for review.
    The Department of Health and Human Services (HHS) issued 45 CFR 
part 46, subpart D, ``Additional Protections for Children Involved as 
Subjects in Research'' as a final rule on March 8, 1983 (48 FR 9814). 
FDA issued part 50, subpart D (21 CFR part 50, subpart D), ``Additional 
Safeguards for Children in Clinical Investigations of Food and Drug 
Administration-Regulated Products,'' as a final rule on February 26, 
2013 (78 FR 12937). These regulations, hereinafter referred to 
collectively as subpart D, are similar, with some minor differences. 
(For a full discussion of the differences between FDA and HHS human 
subject protection regulations, see 78 FR 12937-12947.)
    FDA's part 50, subpart D regulations apply to clinical 
investigations regulated by FDA as described in 21 CFR 50.1(a). HHS 
regulations apply to all research involving human subjects conducted or 
supported by HHS in accordance with 45 CFR 46.101(a). FDA-regulated 
clinical investigations conducted or supported by HHS are subject to 
both sets of regulations. As a result, many sponsors, investigators, 
and IRBs need to be familiar and comply with both FDA's and HHS's 
regulations.
    The draft guidance describes an overview of the review process as 
it relates to FDA referral and review (Sec.  50.54), OHRP referral and 
review (45 CFR 46.407), joint FDA and OHRP review, multisite research, 
and FDA and OHRP review of similar research. This draft guidance is 
being issued consistent with FDA's good guidance practices regulation 
(21 CFR 10.115). The draft guidance, when finalized, will represent the 
current thinking of FDA on research involving children as subjects not 
otherwise approvable by an IRB and the process for referrals to FDA and 
OHRP. It does not establish any rights for any person and is not 
binding on FDA or the public. You can use an alternative approach if it 
satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (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 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.

[[Page 19312]]

Protection of Human Subjects and Institutional Review Boards

OMB Control Number 0910-0130--Revision

    This information collection supports FDA regulations governing 
requirements for informed consent and IRBs that are intended to protect 
the rights and safety of human subjects involved in FDA-regulated 
clinical investigations (parts 50 and 56 (21 CFR parts 50 and 56)). A 
``clinical investigation'' is any experiment that involves a test 
article and one or more human subjects and is subject to requirements 
for prior submission to FDA under section 505(i) or 520(g) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(i) or 
360j(g)), or is not subject to requirements for prior submission to FDA 
under these sections of the FD&C Act, but the results of which are 
intended to be submitted later to, or held for inspection by, FDA as 
part of an application for a research or marketing permit (Sec.  50.3).
    Under Sec.  50.54, FDA will accept IRB referrals of clinical 
investigations involving children as subjects that are not otherwise 
approvable by an IRB under part 50 subpart D. The collections of 
information in parts 50 and 56 are currently approved under OMB control 
number 0910-0130; however, the submission of records to FDA as part of 
an IRB referral under Sec.  50.54, as recommended in the draft guidance 
document, is not called for in the regulations themselves. We are 
therefore revising the information collection to include submissions of 
records to the Agency that may occur under Sec.  50.54. Based on a 
review of Agency data regarding the frequency of IRB referrals under 
Sec.  50.54, we expect that fewer than one such submission would be 
made annually. The records that the draft guidance recommends be sent 
to FDA as part of an IRB's referral are records that are kept by IRBs 
in the ordinary course of their business, and where necessary, 
information collections related to the creation and retention of these 
documents are already approved under OMB control number 0910-0130. We 
assume that no more than 1 hour would be needed to complete the task of 
transmitting this existing information to FDA in accordance with the 
draft guidance recommendations. We invite comment on our estimate and 
assumptions.
    This draft guidance also refers to previously approved collections 
of information by HHS' OHRP under OMB control numbers 0990-0481 and 
0990-0260. Specifically, on February 14, 2022, OMB approved the 
collection of information identified with the OMB control number 0990-
0481 without change. The approved collection of information consists of 
a requirement that IRB records be submitted when an IRB or its 
institution request an HHS consultation process for proposed research 
involving, respectively: (1) pregnant women, human fetuses or neonates; 
(2) prisoners; or (3) children, as subjects that are not otherwise 
approvable by an IRB.
    This draft guidance also refers to previously approved FDA 
collections of information. The collections of information in 21 CFR 
part 312 have been approved under OMB control number 0910-0014, the 
collections of information in 21 CFR part 812 have been approved under 
OMB control number 0910-0078.

III. Electronic Access

    Persons with access to the internet may obtain an electronic 
version of the draft guidance at either https://www.fda.gov/regulatory-information/search-fda-guidance-documents or https://www.regulations.gov.

    Dated: March 27, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-06649 Filed 3-30-23; 8:45 am]
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