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[Federal Register Volume 90, Number 4 (Tuesday, January 7, 2025)]
[Notices]
[Pages 1171-1173]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31527]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-3334]

Accelerated Approval and Considerations for Determining Whether a 
Confirmatory Trial is Underway; Draft Guidance for Industry; 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the availability of a draft guidance for industry entitled 
``Accelerated Approval and Considerations for Determining Whether a 
Confirmatory Trial is Underway.'' For drugs granted accelerated 
approval, sponsors conduct confirmatory studies that must be completed 
postapproval to verify and describe the anticipated effect on 
irreversible morbidity or mortality or other clinical benefit. This 
draft guidance describes FDA's interpretation of the term ``underway'' 
and discusses policies for implementing this requirement, including 
factors FDA intends to consider when determining whether a confirmatory 
trial is underway prior to accelerated approval.

[[Page 1172]]

DATES: Submit either electronic or written comments on the draft 
guidance by March 10, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance. Submit electronic or written comments on the 
proposed collection of information in the draft guidance by March 10, 
2025.

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-2024-D-3334 for ``Accelerated Approval and Considerations for 
Determining Whether a Confirmatory Trial is Underway.'' 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. 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: Tamy Kim, Oncology Center of 
Excellence, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 2206, Silver Spring, MD 20993-0002, 301-796-1125, or 
James Myers, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993-0002, 240-402-7911, or Dat Doan, Center for 
Drug Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3334, Silver Spring, MD 20993-0002, 240-
402-8926 or 301-796-2500.
    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 is announcing the availability of a draft guidance for industry 
entitled ``Accelerated Approval and Considerations for Determining 
Whether a Confirmatory Trial is Underway.'' For drugs granted 
accelerated approval, sponsors have been required to conduct 
confirmatory studies postapproval to verify and describe the 
anticipated effect on irreversible morbidity or mortality or other 
clinical benefit. In the Consolidated Appropriations Act, 2023 (CAA), 
Congress amended section 506(c) of the Federal Food, Drug, and Cosmetic 
Act (FD&C Act) (21 U.S.C. 356(c)), to provide additional authorities to 
help ensure timely completion of such trials, including that FDA ``may 
require, as appropriate, a study or studies to be underway prior to 
approval, or within a specified time period after the date of approval, 
of the applicable product. This draft guidance, when finalized, will 
describe FDA's interpretation of the term ``underway'' and policies for 
implementing this requirement, including factors FDA intends to 
consider when determining whether a confirmatory trial is underway 
prior to an accelerated approval action.
    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 ``Accelerated 
Approval and Considerations for Determining Whether a Required Post-
Marketing Clinical Trial is Underway.'' 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

[[Page 1173]]

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.

Accelerated Approval and Considerations for Determining Whether a 
Confirmatory Trial is Underway

OMB Control Number 0910-0001--Revision
    As noted, section 506 of the FD&C Act was modified by section 3210 
of the CAA, which granted FDA additional authorities with additional 
obligations regarding the accelerated approval pathway. Among other 
revisions, section 3210 of the CAA provides statutory authority to help 
ensure timely completion of confirmatory trials of accelerated approval 
products, including that FDA may require as appropriate, a confirmatory 
study or studies to be underway prior to approval or within a specified 
time period after the date of approval of the product. The CAA also 
requires sponsors to submit postmarketing reports to FDA on the 
progress of required confirmatory trials approximately every 180 days. 
This draft guidance describes FDA's policies for implementing this 
statutory authority. FDA will use the reports to monitor the progress 
of confirmatory trials and take action, if necessary. The information 
is needed to support FDA's efforts to protect the health of users of 
drugs approved under accelerated approval. We are requesting approval 
to revise the statutory authority reference in approved OMB control 
numbers 0910-0001 and 0910-0338 to include section 3210 of the CAA.
    Description of Respondents: Respondents to this information 
collection are sponsors of human drug and biological products.
    Burden Estimate: We reviewed the statutory authority granted by 
section 3210 of the CAA as well as our existing statutory authority and 
regulations. Section 506B of the FD&C Act (21 U.S.C. 356b), and 
implementing regulations in Sec. Sec.  312.20, 314.81 and 601.70 (21 
CFR 312.20, 314.81 and 601.70), provide for the submission of 
postmarket study reports, requiring sponsors of approved drugs and 
biological products to report to FDA on the progress of their 
postmarketing study commitments, including reports on required studies, 
clinical trials, and agreed upon commitments.
    We tentatively conclude that the change in our statutory authority 
adds no further information collection requirements and imposes no 
further burden beyond what is already required in our statutes and 
regulations and included in the approved ICRs for reporting the status 
of postmarketing study commitments.
    This draft guidance also refers to previously approved FDA 
collections of information. The collections of information in 21 CFR 
parts 50 and 56 for protection of human subjects and institutional 
review boards have been approved under OMB control number 0910-0130. 
The collections of information in 21 CFR part 312 for submission of 
investigational new drug applications, conduction of clinical trials 
and good clinical practice, meetings for design and implementation of 
drug development plans, and reports of data for confirmatory trials 
have been approved under OMB control number 0910-0014. The collections 
of information in 21 CFR part 314 for submission of new drug 
applications and abbreviated new drug applications have been approved 
under OMB control number 0910-0001. The collections of information in 
Sec. Sec.  312.20, 314.81 and 601.70 for submission of postmarketing 
reports including accelerated approval clinical benefit studies have 
been approved under OMB control numbers 0910-0014, 0910-0001, and 0910-
0338. The collections of information in 21 CFR parts 601 and 610 for 
submission of biologics license applications have been approved under 
OMB control number 0910-0338. The collections of information for 
expedited pathways for development programs of drugs and biologics for 
serious conditions have been approved under OMB control number 0910-
0765.

III. Electronic Access

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

    Dated: December 27, 2024.
Kimberlee Trzeciak,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2024-31527 Filed 1-6-25; 8:45 am]
BILLING CODE 4164-01-P
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