Federal Register, Volume 90 Issue 180 (Friday, September 19, 2025)

[Federal Register Volume 90, Number 180 (Friday, September 19, 2025)]
[Notices]
[Pages 45220-45221]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-18152]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0164]


Safety Labeling Changes--Implementation of Section 505(o)(4) of 
the Federal Food, Drug, and Cosmetic Act; Draft Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Safety 
Labeling Changes--Implementation of Section 505(o)(4) of the Federal 
Food, Drug, and Cosmetic Act.'' This draft guidance provides 
information on the implementation of the statutory provision that 
authorizes FDA to require application holders for certain drug and 
biological products to make labeling changes based on new safety 
information that becomes available after approval of the drug that FDA 
determines should be included in the labeling of the drug. This 
guidance is being updated and reissued in draft to, among other things, 
include the addition of information related to Congress' 2018 changes 
to the definition of adverse drug experience regarding reduced 
effectiveness and make other changes to reflect current Agency 
processes and procedures regarding safety labeling changes. This draft 
guidance revises and, when finalized, will replace the guidance for 
industry entitled ``Safety Labeling Changes--Implementation of Section 
505(o)(4) of the FD&C Act'' issued in July 2013.

DATES: Submit either electronic or written comments on the draft 
guidance by November 18, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

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-2011-D-0164 for ``Safety Labeling Changes--Implementation of 
Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act.'' 
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 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 the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3103 Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Kimberly Lehrfeld, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6250, Silver Spring, MD 20993-0002, 301-
796-3137, [email protected] or Phillip Kurs, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 240-
402-7911.

SUPPLEMENTARY INFORMATION:

[[Page 45221]]

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Safety Labeling Changes--Implementation of Section 505(o)(4) 
of the Federal Food, Drug, and Cosmetic Act.'' Section 505(o)(4) of the 
FD&C Act (21 U.S.C. 355(o)(4)) authorizes FDA to require application 
holders for certain drugs \1\ to make labeling changes based on new 
safety information, including information related to reduced 
effectiveness, that becomes available after approval of the drug that 
FDA determines should be included in the labeling of the drug.
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    \1\ For the purposes of the Safety Labeling Changes--
Implementation of Section 505(o)(4) of the Federal Food, Drug, and 
Cosmetic Act Guidance for Industry, references to drug include drug 
products approved under section 505 of the FD&C Act (21 U.S.C. 355) 
and biological products licensed under section 351 of the Public 
Health Service Act (42 U.S.C. 262), other than biological products 
that also meet the definition of a device in section 201(h) of the 
FD&C Act (21 U.S.C. 321(h)).
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    In the Federal Register of July 30, 2013 (78 FR 45930), FDA 
announced the availability of a guidance for industry entitled ``Safety 
Labeling Changes--Implementation of Section 505(o)(4) of the Federal 
Food, Drug, and Cosmetic Act'' (available at https://www.fda.gov/media/116594/download) (the 2013 guidance). The 2013 guidance provided 
information on the implementation of section 505(o)(4) of the FD&C Act, 
including a description of the types of safety labeling changes (SLCs) 
that generally may be required under this section; how FDA determines 
what constitutes new safety information; the procedures involved in 
requiring SLCs; and enforcement of the requirements for SLCs.
    In 2018, Congress enacted the Substance Use-Disorder Prevention 
that Promotes Opioid Recovery and Treatment for Patients and 
Communities Act (Pub. L. 115-271) (SUPPORT Act) which, among other 
things, changed the statutory definition of adverse drug experience in 
section 505-1(b)(1) of the FD&C Act. The SUPPORT Act also revised 
section 505(o)(4) of FD&C Act to define new information to include 
``information related to reduced effectiveness.''
    This draft guidance revises and, when finalized, will replace the 
guidance for industry of the same name issued on July 30, 2013 (78 FR 
45930). Updates in this draft guidance include the addition of 
information related to Congress' 2018 changes to the definition of 
adverse drug experience regarding reduced effectiveness such as the 
clarification that the Agency can require changes to labeling to 
include information about a serious risk that results from reduced 
effectiveness. Additional changes were made reflecting current SLC 
processes and procedures adding a description of how FDA reviews and 
acts on SLCs when new safety information applies to multiple 
application holders, and clarifying when FDA may disclose SLC 
notification and order letters.
    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 ``Safety 
Labeling Changes--Implementation of Section 505(o)(4) of the FD&C 
Act.'' 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.
    As we develop final guidance on this topic, FDA will consider 
comments on costs or cost savings the guidance may generate, relevant 
for Executive Order 14192.

II. The Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information 
in 21 CFR part 314 pertaining to the submission of new drug 
applications (NDAs), abbreviated new drug applications (ANDAs), and 
supplements to NDAs and ANDAs have been approved under OMB control 
number 0910-0001. The collections of information in 21 CFR part 601 
pertaining to biologics license applications (BLAs) and supplements to 
BLAs have been approved under OMB control number 0910-0338. The 
collections of information pertaining to medication guides for 
prescription drug products have been approved under OMB control number 
0910-0393. The collections of information pertaining to the labeling of 
human prescription drug and biological products have been approved 
under OMB control number 0910-0572.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or https://www.regulations.gov.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-18152 Filed 9-18-25; 8:45 am]
BILLING CODE 4164-01-P