Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 1171 

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 § 10.115(g)(5) 

(21 CFR 10.115(g)(5))). 

Submit written requests for single 

copies of the guidance to the Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research (CBER), Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

two self-addressed adhesive labels to 

assist that office in processing your 

requests. The guidance may also be 

obtained by mail by calling CBER at 1– 

800–835–4709 or 240–402–8010. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Jessica Gillum, 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. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a final guidance for immediate 

implementation entitled 

‘‘Recommendations To Reduce the Risk 

of Transmission of Mycobacterium 

Tuberculosis (Mtb) by Human Cells, 

Tissues, and Cellular and Tissue-Based 

Products (HCT/Ps).’’ FDA is issuing this 

guidance to provide establishments that 

make donor eligibility determinations 

for donors of HCT/Ps with 

recommendations for screening for 

evidence of, and risk factors for, 

infection with Mtb, the organism that 

causes tuberculosis. The guidance also 

recommends additional steps that HCT/ 

P establishments should take to reduce 

risk of transmission of Mtb until such 

time as appropriate FDA-licensed, 

approved, or cleared donor screening 

tests are available for use to test donors 

for Mtb infection. 

In addition, this guidance identifies 

Mtb as an RCDAD as defined in 21 CFR 

1271.3(r)(2) and supplements the 

recommendations contained in other 

donor eligibility guidance documents 

for donors of HCT/Ps. 

In 2021 and 2023, multistate 

outbreaks of Mtb in the United States 

were linked to transplantation of bone 

allograft products and resulted in 

significant morbidity and mortality. 

Because Mtb transmission can occur 

from HCT/P donors with unrecognized 

and undiagnosed tuberculosis infection, 

these circumstances demand heightened 

awareness when screening donors of 

HCT/Ps. 

We are issuing this guidance 

consistent with our good guidance 

practices (GGP) regulation (§ 10.115 (21 

CFR 10.115)). We are implementing this 

guidance without prior public comment 

because we have determined that prior 

public participation is not feasible or 

appropriate (§ 10.115(g)(2)). We made 

this determination because of the urgent 

public health need to provide 

recommendations to industry to reduce 

the risk of transmission of Mtb by HCT/ 

Ps. Although this guidance document is 

immediately in effect, it remains subject 

to comment in accordance with FDA’s 

GGP. 

Elsewhere in this issue of the Federal 

Register, FDA is announcing the 

availability of another immediately in 

effect guidance entitled 

‘‘Recommendations To Reduce the Risk 

of Transmission of Disease Agents 

Associated with Sepsis by Human Cells, 

Tissues, and Cellular and Tissue-Based 

Products (HCT/Ps)’’ with 

recommendations to reduce the risk of 

transmission of disease agents 

associated with sepsis, including 

mycobacterial agents such as Mtb, 

which can be a cause of sepsis. 

The guidance represents the current 

thinking of FDA on ‘‘Recommendations 

To Reduce the Risk of Transmission of 

Mycobacterium Tuberculosis (Mtb) by 

Human Cells, Tissues, and Cellular and 

Tissue-Based Products (HCT/Ps).’’ 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 1271 relating to 

HCT/Ps, including establishing and 

maintaining records, investigation and 

reporting of adverse actions and 

documentation of methods used in 

facilities related to HCT/Ps, which, 

includes but not limited to donor 

screening, donor testing, and labeling 

have been approved under OMB control 

number 0910–0543. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at https://

www.fda.gov/vaccines-blood-biologics/ 

guidance-compliance-regulatoryinformation-biologics/biologicsguidances, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. Use the FDA 

website listed in the previous sentence 

to find the most current version of the 

guidance. 

Dated: December 27, 2024. 

Kimberlee Trzeciak, 

Deputy Commissioner for Policy, Legislation, 

and International Affairs. 

[FR Doc. 2024–31544 Filed 1–6–25; 8:45 am] 

BILLING CODE 4164–01–P 

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. 

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. 


ddrumheller on DSK120RN23PROD with NOTICES1
1172 Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 

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, PRAStaff@fda.hhs.gov. 

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 


ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 90, No. 4 / Tuesday, January 7, 2025 / Notices 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 

§§ 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 §§ 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/guidancecompliance-regulatory-information/ 

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

regulatory-information/search-fdaguidance-documents, https://

www.fda.gov/vaccines-blood-biologics/ 

guidance-compliance-regulatoryinformation-biologics/biologicsguidances, 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2024–D–2402] 

Considerations for Including Tissue 

Biopsies in Clinical Trials; Draft 

Guidance for Industry, Investigators, 

Institutions, and Institutional Review 

Boards; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) and 

the Office for Human Research 

Protections (OHRP) are announcing the 

availability of a draft guidance for 

industry, clinical investigators, 

institutions, and institutional review 

boards (IRBs) entitled ‘‘Considerations 

for Including Tissue Biopsies in Clinical 

Trials.’’ This guidance provides 

recommendations regarding 

considerations for tissue biopsies that 

may be conducted in adults and in 

children as part of clinical trials 

evaluating investigational medical 

products and/or that are conducted or 


ddrumheller on DSK120RN23PROD with NOTICES1