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[Federal Register Volume 89, Number 230 (Friday, November 29, 2024)]
[Notices]
[Pages 94738-94740]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-28033]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0084]

Use of Circulating Tumor Deoxyribonucleic Acid for Curative-
Intent Solid Tumor Drug Development; 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 final guidance for industry entitled ``Use of 
Circulating Tumor DNA for Curative-Intent Solid Tumor Drug 
Development.'' This guidance is intended to help sponsors planning to 
use circulating cell-free plasma derived tumor DNA (ctDNA) as a 
biomarker in cancer clinical trials conducted under an investigational 
new drug application (IND) and/or to support marketing approval of 
drugs and biological products for treating solid tumor malignancies in 
the early-stage (curative-intent) setting. This guidance finalizes the 
draft guidance entitled ``Use of Circulating Tumor DNA for Early-Stage 
Solid Tumor Drug Development'' issued on May 2, 2022.

DATES: The announcement of the guidance is published in the Federal 
Register on November 29, 2024.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances 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-0084 for ``Use of Circulating

[[Page 94739]]

Tumor Deoxyribonucleic Acid for Curative-Intent Solid Tumor Drug 
Development.'' 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 this 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; Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or 
Office of Policy, Center for Devices and Radiological Health, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, 
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 guidance document.

FOR FURTHER INFORMATION CONTACT: Paz Vellanki, Center for Drug 
Evaluation and Research (HFD-150), Food and Drug Administration, 10903 
New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-9366; James 
Myers, Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver 
Spring, MD 20993, 240-402-7911; or Center for Devices and Radiological 
Health, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Use of Circulating Tumor DNA for Curative-Intent Solid Tumor 
Drug Development.'' This guidance is intended to help sponsors planning 
to use circulating cell-free plasma derived tumor DNA (ctDNA) as a 
biomarker in cancer clinical trials conducted under an IND and/or to 
support marketing approval of drugs and biological products for 
treating solid tumor malignancies in the early-stage (curative-intent) 
setting.
    Certain patients with early-stage solid tumors can be cured with 
local therapy alone (e.g., surgery, radiation, or chemoradiation), 
other patients require (neo)adjuvant systemic therapy in order to be 
cured, and others may progress to metastatic disease despite surgery 
and/or systemic therapy. ctDNA is tumor-derived fragmented DNA shed 
into a patient's bloodstream that is not associated with cells. ctDNA 
quantity can vary among individuals and depends on the type of tumor, 
location, stage, tumor burden, and response to therapy. ctDNA as a 
biomarker has a number of potential regulatory and clinical uses in the 
early-stage setting that may assist and expedite drug development. In 
the early-stage cancer setting, ctDNA may be used to detect a certain 
targetable alteration, to enrich a high- or low-risk population for 
study in a trial, to reflect a patient's response to treatment, or, 
potentially, as an early marker of efficacy.
    This guidance finalizes the draft guidance entitled, ``Use of 
Circulating Tumor DNA for Early-Stage Solid Tumor Drug Development,'' 
issued on May 2, 2022 (87 FR 26207). FDA considered comments received 
on the draft guidance as the guidance was finalized. Changes from the 
draft to the final guidance include edits to further explain the 
rationale for writing a guidance on use of ctDNA for solid tumor drug 
development specific to the early-stage, curative-intent disease 
setting. The part of the guidance that discusses assay considerations 
was also clarified to indicate that while a major focus of this section 
pertains to assessment of molecular residual disease (MRD), there may 
be other uses of ctDNA in the early-stage disease setting. In addition, 
editorial changes were made to improve clarity.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Use of Circulating Tumor DNA for Curative-
Intent Solid Tumor Drug Development.'' 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

    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 parts 50 and 56 have been approved under OMB control number 
0910-0130; the collections of information in 21 CFR part 314 have been 
approved under OMB control number 0910-0001; 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 601 
have been approved under OMB control number 0910-0338; the collections 
of information in 21 CFR part 800 have been approved under OMB control 
number 0910-0625; and the collections of information pertaining to 
submission of a biologics license application under section 351(k) of 
the Public Health Service Act (42 U.S.C. 262(k)) have been approved 
under OMB control number 0910-0718.

[[Page 94740]]

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
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, 
https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: November 19, 2024.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2024-28033 Filed 11-27-24; 8:45 am]
BILLING CODE 4164-01-P
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