11720 Federal Register / Vol. 87, No. 41 / Wednesday, March 2, 2022 / Notices 

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. 

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copies of the draft guidance to the 

Policy and Regulations Staff (HFV–6), 

Center for Veterinary Medicine, Food 

and Drug Administration, 7519 Standish 

Pl., Rockville, MD 20855. Send one selfaddressed 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: 

Regarding tracers used in animal food: 

Diego Paiva, Center for Veterinary 

Medicine (HFV–229), Food and Drug 

Administration, 7519 Standish Place, 

Rockville, MD 20855, 240–402–6785, 

Diego.Paiva@fda.hhs.gov; regarding 

tracers used in animal drug products: 

Rebecca Owen, Center for Veterinary 

Medicine (HFV–141), Food and Drug 

Administration, 7500 Standish Place, 

Rockville, MD 20855, 240–402–0670, 

Rebecca.Owen@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry #258 

entitled ‘‘Use of Tracers in Animal 

Food, Type A Medicated Articles, and 

Medicated Feeds.’’ FDA’s Center for 

Veterinary Medicine receives inquiries 

regarding the use of ‘‘tracers’’ in animal 

food, medicated feeds, and Type A 

medicated articles. Tracers are 

ingredients added to these products to 

identify a particular product. The 

purpose of this document is to provide 

guidance on the use of tracers in animal 

food, medicated feeds, and Type A 

medicated articles. When finalized, this 

guidance will replace CPG Sec. 680.100 

Tracers in Animal Feed. 

This level 1 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 the use of tracers in 

animal food, Type A medicated articles, 

and medicated feeds. 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. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR 501.22 have been 

approved under OMB control number 

0910–0721. The collections of 

information in 21 CFR part 514 have 

been approved under OMB control 

number 0910–0032. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/AnimalVeterinary/ 

GuidanceComplianceEnforcement/ 

GuidanceforIndustry/default.htm, 

https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments, or https://

www.regulations.gov. 

Dated: February 24, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–04370 Filed 3–1–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2018–D–2777] 

Expansion Cohorts: Use in First-inHuman Clinical Trials To Expedite 

Development of Oncology Drugs and 

Biologics; 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 

‘‘Expansion Cohorts: Use in First-inHuman Clinical Trials to Expedite 

Development of Oncology Drugs and 

Biologics.’’ The purpose of this 

guidance is to provide advice to 

sponsors regarding the design and 

conduct of first-in-human (FIH) clinical 

trials intended to efficiently expedite 

the clinical development of oncology 

drugs, including biological products, 

through multiple expansion cohort trial 

designs. This guidance finalizes the 

draft guidance of the same name issued 

in August 2018. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on March 2, 2022. 

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 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 87, No. 41 / Wednesday, March 2, 2022 / Notices 11721 

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– 

2018–D–2777 for ‘‘Expansion Cohorts: 

Use in First-in-Human Clinical Studies 

to Expedite Development of Oncology 

Drugs and Biologics.’’ 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; 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. 

3128, 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: Lee 

Pai-Scherf, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, Rm. 2314, Silver Spring, 

MD 20993–0002, 240–402–7911; or 

Stephen Ripley, 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 industry entitled 

‘‘Expansion Cohorts: Use in First-inHuman Clinical Trials to Expedite 

Development of Oncology Drugs and 

Biologics.’’ The purpose of this 

guidance is to provide advice to 

sponsors regarding the design and 

conduct of FIH clinical trials intended 

to efficiently expedite the clinical 

development of oncology drugs, 

including biological products, through 

multiple expansion cohort trial designs. 

These are trial designs that employ 

multiple, concurrently accruing, subject 

cohorts, where individual cohorts assess 

different aspects of the safety, 

pharmacokinetics, and antitumor 

activity of the drug product. This 

guidance provides FDA’s current 

thinking regarding (1) characteristics of 

drug products best suited for 

consideration for development under a 

multiple expansion cohort trial; (2) 

information to include in investigational 

new drug application submissions to 

support the use of individual cohorts; 

(3) when to interact with FDA on 

planning and conducting multiple 

expansion cohort trials; and (4) 

safeguards to protect subjects enrolled 

in FIH expansion cohort trials. 

This guidance finalizes the draft 

guidance of the same name issued 

August 13, 2018 (83 FR 40055). Changes 

made to the guidance took into 

consideration public comments 

received. Major changes from the draft 

to the final guidance include the 

following: 

• Language added stating that designs 

other than Simon two-stage (e.g., 

Bayesian statistical design) may be used 

to assess antitumor activity in a 

nonrandomized cohort to limit the 

number of subjects that could be 

exposed to a potentially ineffective 

drug. 

• Statement added to indicate that in 

trials of limited sample size, a safety 

assessment committee could be a group 

within the sponsor’s organization alone 

that is not otherwise involved in trial 

conduct or management or with external 

representation in lieu of an independent 

data monitoring committee. 

• Language added to state that 

development of an age-appropriate 

formulation may be necessary for 

pediatric populations. 

• Minor changes added to various 

sections to clarify criteria for drug 

products suitable for investigation in 

clinical trials with FIH multiple 

expansion cohorts, the procedure for 

obtaining a risk assessment if an in vitro 

diagnostic will be used for patient 

management, and the information to be 

submitted to the FDA to support 

amendments to expand the protocol. 

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 ‘‘Expansion Cohorts: 

Use in First-in-Human Clinical Trials to 

Expedite Development of Oncology 

Drugs and Biologics.’’ 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. Therefore, clearance by the 

Office of Management and Budget 


lotter on DSK11XQN23PROD with NOTICES1
11722 Federal Register / Vol. 87, No. 41 / Wednesday, March 2, 2022 / Notices 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. 

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 58 for good 

laboratory practices for nonclinical 

laboratory studies have been approved 

under OMB control number 0910–0119. 

The collections of information in 

§§ 201.56 and 201.57 have been 

approved under OMB control number 

0910–0572. The collections of 

information in 21 CFR part 312 that 

support FDA’s regulations for 

investigational new drug applications 

have been approved under OMB control 

number 0910–0014. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001. 

The collections of information in 

biologics license applications submitted 

under 21 CFR part 601 have been 

approved under OMB control number 

0910–0338. The collections of 

information in 21 CFR part 812 have 

been approved under OMB control 

number 0910–0078. 

The collections of information in the 

guidance for industry entitled 

‘‘Oversight of Clinical Investigations—A 

Risk-Based Approach to Monitoring’’ 

(available at https://www.fda.gov/ 

media/116754/download) have been 

approved under OMB control number 

0910–0733. The collections of 

information in the guidance for industry 

entitled ‘‘Expedited Programs for 

Serious Conditions—Drugs and 

Biologics’’ (available at https://

www.fda.gov/media/86377/download) 

have been approved under OMB control 

number 0910–0765. 

The collections of information in the 

International Council for Harmonisation 

guidance for industry entitled ‘‘E6(R2) 

Good Clinical Practice: Integrated 

Addendum to ICH E6(R1)’’ (available at 

https://www.fda.gov/media/93884/ 

download) have been approved under 

OMB control number 0910–0843. The 

collections of information in the 

guidance for industry entitled ‘‘Formal 

Meetings Between the FDA and 

Sponsors or Applicants of PDUFA 

Products’’ (available at https://

www.fda.gov/media/109951/download) 

have been approved under OMB control 

number 0910–0429. 

The collections of information 

regarding evaluation of the program for 

enhanced review transparency and 

communication for new molecular 

entity new drug applications and 

original biologics license applications in 

the Prescription Drug User Fee Act have 

been approved under OMB control 

number 0910–0746. 

The collections of information 

described in the guidance for industry 

and review staff entitled ‘‘Formal 

Dispute Resolution: Sponsor Appeals 

Above the Division Level’’ (available at 

https://www.fda.gov/media/126910/ 

download) have been approved under 

OMB control number 0910–0430. 

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, https://www.fda.gov/ 

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

www.regulations.gov. 

Dated: February 24, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–04397 Filed 3–1–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2018–D–3292] 

Master Protocols: Efficient Clinical 

Trial Design Strategies To Expedite 

Development of Oncology Drugs and 

Biologics; 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 ‘‘Master 

Protocols: Efficient Clinical Trial Design 

Strategies to Expedite Development of 

Oncology Drugs and Biologics.’’ This 

guidance provides advice to sponsors of 

drugs and biologics for cancer treatment 

regarding the design and conduct of 

clinical trials, other than first-in-human 

trials, intended to simultaneously 

evaluate more than one investigational 

drug and/or more than one cancer type 

within the same overall trial structure 

(master protocols) in adult and pediatric 

cancers. In contrast to traditional trial 

designs, where a single drug is tested in 

a single disease population in one 

clinical trial, master protocols use a 

single infrastructure, trial design, and 

protocol to simultaneously evaluate 

multiple drugs and/or disease 

populations in multiple substudies, 

allowing for efficient and accelerated 

drug development. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on March 2, 2022. 

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– 

2018–D–3292 for ‘‘Master Protocols: 

Efficient Clinical Trial Design Strategies 

to Expedite Development of Oncology 

Drugs and Biologics.’’ Received 

comments will be placed in the docket 


lotter on DSK11XQN23PROD with NOTICES1