94738 Federal Register / Vol. 89, No. 230 / Friday, November 29, 2024 / Notices 

TABLE 3—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

21 CFR section Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeping 

Total 

hours 2

Recordkeeping—54.6 ...................................................... 712 1 712 0.25 178 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

2 Numbers have been rounded. 

Third-Party Disclosure Burden 

Under § 54.4(b), clinical investigators 

supply to the sponsor of a covered study 

financial information sufficient to allow 

the sponsor to submit complete and 

accurate certification or disclosure 

statements. Clinical investigators are 

accustomed to supplying such 

information when applying for research 

grants. Also, most people know the 

financial holdings of their immediate 

family and records of such interests are 

generally accessible because they are 

needed for preparing tax records. For 

these reasons, FDA estimates that the 

time required for this task may range 

from 5 to 15 minutes; we used the 

median, 10 minutes, for the average 

burden per disclosure (see table 4). To 

estimate the number of respondents for 

each FDA Center, we took the median 

number of investigators for each 

application type, multiplied each 

median number of investigators by the 

number of affected applications for that 

application type, then summed those 

products to get the total number of 

respondents for the Center. 

TABLE 4—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

21 CFR section Number of 

respondents 

Number of 

disclosures per 

respondent 

Total annual 

disclosures 

Average 

burden per 

disclosure 

Total 

hours 2

54.4(b)—Clinical Investigators ......................................... 13,646 1 13,646 0.17 2,320 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

2 Numbers have been rounded. 

The burden for this information 

collection request has changed since the 

last OMB approval. We have adjusted 

our estimated burden for the 

information collection to reflect the 

number of submissions we received in 

the last few years. These adjustments 

result in an increase of 557 total annual 

responses and a corresponding increase 

of 87 total hours. 

Dated: November 19, 2024. 

P. Ritu Nalubola, 

Associate Commissioner for Policy. 

[FR Doc. 2024–28034 Filed 11–27–24; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2022–D–0084] 

Use of Circulating Tumor 

Deoxyribonucleic Acid for CurativeIntent Solid Tumor Drug Development; 

Guidance for Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

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 CurativeIntent 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 


khammond on DSK9W7S144PROD with NOTICES
Federal Register / Vol. 89, No. 230 / Friday, November 29, 2024 / Notices 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 selfaddressed 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, 

CDRHClinicalEvidence@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled ‘‘Use of 

Circulating Tumor DNA for CurativeIntent 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 tumorderived 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. 


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94740 Federal Register / Vol. 89, No. 230 / Friday, November 29, 2024 / Notices 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at https://

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, https:// 

www.fda.gov/medical-devices/deviceadvice-comprehensive-regulatoryassistance/guidance-documentsmedical-devices-and-radiation-emittingproducts, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–N–4687] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Medicated Feed 

Mill License Application 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

announcing an opportunity for public 

comment on the proposed collection of 

certain information by the Agency. 

Under the Paperwork Reduction Act of 

1995 (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 information 

collection provisions of medicated feed 

mill license reporting. 

DATES: Either electronic or written 

comments on the collection of 

information must be submitted by 

January 28, 2025. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. The https://

www.regulations.gov electronic filing 

system will accept comments until 

11:59 p.m. Eastern Time at the end of 

January 28, 2025. Comments received by 

mail/hand delivery/courier (for written/ 

paper submissions) will be considered 

timely if they are received on or before 

that date. 

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–N–4687 for ‘‘Agency Information 

Collection Activities; Proposed 

Collection; Comment Request; 

Medicated Feed Mill License 

Application.’’ Received comments, 

those filed in a timely manner (see 

ADDRESSES), 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. 

FOR FURTHER INFORMATION CONTACT: 

JonnaLynn Capezzuto, Office of 

Operations, Food and Drug 

Administration, Three White Flint 

North, 10A–12M, 11601 Landsdown St., 

North Bethesda, MD 20852, 301–796– 

3794, PRAStaff@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Under the 

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 


khammond on DSK9W7S144PROD with NOTICES